green chemistry using bismuth compounds: bismuth(iii) triflate
TRANSCRIPT
Illinois Wesleyan UniversityDigital Commons @ IWU
Honors Projects Chemistry
2009
Green Chemistry Using Bismuth Compounds:Bismuth(III) Triflate Catalyzed Allylation of CyclicAcetalsMatthew J. Spafford, '09Illinois Wesleyan University
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Recommended CitationSpafford, '09, Matthew J., "Green Chemistry Using Bismuth Compounds: Bismuth(III) Triflate Catalyzed Allylation ofCyclic Acetals" (2009). Honors Projects. Paper 33.http://digitalcommons.iwu.edu/chem_honproj/33
Green Chemistry Using Bismuth Compounds: Bismuth(III) Triflate Catalyzed Allylation of Cyclic
Acetals
Matthew J. Spafford
Advisor: Dr. Ram Mohan
Research Honors Senior Thesis
Illinois Wesleyan University
Spring 2009
Approval Page i
Green Chemistry Using Bismuth Compounds: Bismuth(III) Triflate Catalyzed Allylation of Cyclic Acetals
By
Matthew 1. Spafford
A PAPER SUBMITTED AS PART OF THE REQUIREMENT FOR RESEARCH HONORS IN CHEMISTRY
Approved:
Ram S. Mohan, Ph. D. , Research Advisor !
Brian B. Brennan, Ph. D.
"�a � Rebecca Roesner, Ph. D.
Nathan Frank, Ph. D.
Illinois Wesleyan University, April 20, 2009
Acknowledgements
I would first like to thank my research advisor and friend, Dr. Ram Mohan, for all his
support and encouragement over the past years. He has instilled a passion for chemistry in me
through his teaching and for that, I am very much indebted to him. His guidance and support has
been instrumental in shaping me as a scientist. I am also very grateful for the countless hours he
has spent on my behalf, without which this dissertation would not have been possible.
I would also like to thank Dr. Brian Brennan, Dr. Rebecca Roesner, and Dr. Nathan
Frank for serving on my thesis committee.
A special thanks is in order for the all members of the research group over the past years:
Aaron Bailey and Erin Anderson for their especial patiertce while training me as a Sophomore;
Scott Krabbe for his synthesis of dioxanes and his wonderful country music collection; Dr.
Eeshwar Begari for his early work on the allylation of dioxanes; Jay Christensen, Matthew
Huddle, and Josh Lacey for their work on the allylation of dioxolanes; Pash DeVore, JP Carolan,
Kendall Tasche, Jason Bothwell, Dan Podgorski, Maggie Olsen, Long Le, Jamie Rogers, Herbie
Yung, Justin Emat, Ashvin Bam, Ann Palma, Veronica Angeles, Paul Sierszulski, and Phil
Lazzara for making time in lab over the past years such a great time.
I also need to acknowledge Cindy Honegger for all of her help in the stockroom over the past
two years. None of this work would have been possible if not for her assistance.
11
The Twelve Principles of Green Chemistry
1. Prevention: It is better to prevent waste than to treat or clean up waste after it has been created.
2. Atom Economy: Synthetic methods should be designed to maximize the incorporation of all materials used in the process into the final product.
3. Less Hazardous Chemical Syntheses: Wherever practicable, synthetic methods should be designed to use and generate substances that possess little or no toxicity to human health and the environment.
4. Designing Safer Chemicals: Chemical products should be designed to effect their desired function while minimizing their toxicity.
5. Safer Solvents and Auxiliaries: The use of auxiliary substances (e.g., solvents, separation agents, etc.) should be made unnecessary wherever possible and innocuous when used.
6. Design for Energy Efficiency: Energy requirements of chemical processes should be recognized for their environmental and economic impacts and should be minimized. If possible, synthetic methods should be conducted at ambient temperature and pressure.
7. Use of Renewable Feedstocks: A raw material or feedstock should be renewable rather than depleting whenever technically and economically practicable.
8. Reduce Derivatives: Unnecessary derivatization (use of blocking groups, protection/deprotection, temporary modification of physical/chemical processes) should be minimized or avoided if possible, because such steps require additional reagents and can generate waste.
9. Catalysis: Catalytic reagents (as selective as possible) are superior to stoichiometric reagents.
10. Design for Degradation: Chemical products should be designed so that at the end of their function they break down into innocuous degradation products and do not persist in the environment.
11. Real-time analysis for Pollution Prevention: Analytical methodologies need to be further developed to allow for real-time, in-process monitoring and control
111
prior to the formation of hazardous substances.
12. Inherently Safer Chemistry for Accident Prevention: Substances and the form of a substance used in a chemical process should be chosen to minimize the potential for chemical accidents, including releases, explosions, and fires.
Anastas, P . T.; Warner, J. C. Green Chemistry, Theory and Practice. Oxford University Press, New York, 1998, 30.
IV
Abstract
x�) R1.-lX n
X=O, S n = 1 , 2
Bi(OTfh (2.0 mol %)
�SiMe3 ( 1 .7 eq)
Cyclic acetals (dioxolanes, dioxanes, and dithianes) are common protecting groups in
organic synthesis but they can also be converted to other useful functional groups. A
bismuth(III) triflate-catalyzed multi component reaction involving the allylation of cyclic acetals
followed by in situ derivatization with acid anhydrides to generate highly functionalized esters
and thioesters has been developed under solvent-free conditions. Most reagents used to date for
the allylation of cyclic acetals are highly corrosive or toxic and are often required in
stoichiometric amounts. In contrast, the use of a relatively non-toxic and non-corrosive
bismuth(III) based catalyst makes this methodology benign and attractive.
v
Table of Contents
I . Introduction.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
A. Green Chemistry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
B. Bismuth Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
C. Literature Review: Allylation of Acetals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 1
II. Results and Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
A. Bismuth(III) Triflate Catalyzed Allylation of 1 ,3-Dioxolanes . . . . . . . . . . . . . . . . . . . . . 32
B. Mechanistic Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 7
C . Bismuth(III) Triflate Catalyzed Allylation of 1 ,3-Dioxanes . . . . . . . . . . . . . . . . . . . . . . . . 39
D. Bismuth(III) Triflate Catalyzed Allylation of 1 ,3-Dithianes . . . . . . . . . . . . . . . . . . . . . . . 4 1
III. Experimental . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
A. General Experimental . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
B. Bismuth(III) Triflate Catalyzed Allylation of 1 ,3-Dioxolanes . . . . . . . . . . . . . . . . . . 46
C. Bismuth(III) Triflate Catalyzed Allylation of5,5-Dimethyl- 1 ,3 -Dioxanes . . . . . 53
D. Bismuth(III) Triflate Catalyzed Allylation of 1 ,3-Dithianes . . . . . . . . . . . . . . . . . . . . . . 56
IV. References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ...... 63
V. Appendix: Spectral Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
VI.
VB
I. Introduction
A. Green Chemistry
The contributions ofthe phannaceutical industry, especially via synthetic organic
chemistry, to medicine have significantly improved the quality and length of human life. The
synthesis and commercial development of countless compounds now allow for the treatment of
diseases that have otherwise overwhelmed mankind. Over the past century, the discovery of
antibiotics and new medicines has contributed to prolonging the average human life span by
nearly thirty years.! The development of new fertilizers and pesticides has allowed for more
bountiful harvests. Despite the vast achievements of the chemical industry, the massive
amounts of hazardous waste produced cannot be ignored, especially when considering current
environmental issues and the hazards presented to human health. For example, in 1 984 a Union
Carbide pesticide plant in Bhopal, India released 42 tons of methyl isocyanate? Nearly 1 5,000
people have lost their lives as result of this toxic gas leak and many others have suffered health
problems due to exposure. Environmental drinking water contamination has also been a major
issue in the aftermath of the disaster.
The United States Congress has passed many laws to help reduce the amount of chemical
waste released into the environment. The most significant of these is the "Pollution Prevention
Act" (PP A) passed in 1 990.3 The PP A provides guidelines and laws on pollution prevention
through the proper use and disposal of chemicals. Also, source reduction and prevention have
been stressed in this legislation. The government tracks the production and release of toxic
chemical waste in the Toxic Release Inventory (TRI).4 In 2006, the TRI indicated that the
chemical industry ranks third in the amount of waste released by sector (figure 1 . 1 ) . The only
1
industries that produce and release more waste are the relatively large metal mining and
electricity sectors.
Figure 1.1: 2006 TID Total Disposal or Release of Waste by Industry4
Hazardous Waste 5%
Paper 5%
Food
Therefore, chemists need to be more concerned with pollution in terms of hazardous
waste being released into the environment. This has prompted synthetic organic chemists to
consider developing environmentally friendly chemistry or Green Chemistry. Green Chemistry
involves the design of chemical syntheses and processes that are more environmentally friendly,
reduce waste production, and avoid use of toxic reagents.2 The main goal of green chemistry is
to minimize the use of toxic chemicals by finding safe, effective alternatives. This type of
developmental strategy is an efficient way to reduce the chemical waste associated with a
synthesis. Also, avoiding the use of toxic and corrosive reagents makes synthesis much safer for
the chemists involved. The risk associated with the use of a chemical can be expressed as a
function of both hazard and exposure (eq. 1 . 1 )?
2
Equation 1.1
Risk = f [hazard, exposure]
Past strategies of reducing risk have involved limiting exposure to dangerous chemicals
by taking safety precautions and exercising especial care when handling reagents. This strategy
can be an effective way of increasing safety if exposure can truly be limited. However, due to
human error and faults in protective laboratory equipment, exposure control measures often fail.
Therefore, the Green Chemistry approach is to lower hazards by using inherently less toxic or
non-toxic reagents. This reduces risk associated with syntheses and reduces hazardous waste
overall. This concept can be accomplished through the practice of Green Chemistry where
information about toxicity of chemicals is utilized to lower hazard and reduce waste. This has
particular relevance to synthetic organic chemistry, a field in which many toxic, corrosive and
difficult to dispose of chemicals continue to be used in large quantities.
One concept that can be used to reduce the amount of waste associated with a chemical
synthesis is atom economy. Atom economy is a measure of the percent by mass of reactants that
end up in the desired product, and hence, is a good indication of the amount of waste material
associated with a process. The solvents and catalysts necessary for a synthesis are not
considered. This concept was introduced by Trost in 1 99 1 .5
Equation 1.2
A E Molecular Weight of desired product 1 0 Of tom conomy = x 070
Molecular Weight of all reactants
Many synthetic methods currently used yield byproducts that increase the amount of
waste associated with a synthesis. Also, if the byproducts are toxic this makes waste disposal
3
more difficult and costly. The Wittig synthesis of alkenes produces one equivalent of
triphenylphosphine oxide as a byproduct for every equivalent of alkene formed (scheme 1 . 1 ).
Scheme 1.1
o A +
o II
+ Ph/�'Ph Ph
In contrast to the Wittig reaction, a classic example of an atom-economic reaction is the Diels-
Alder cycloaddition. All of the atoms present in the diene and dienophile are present in the final
cyclized product. Thus, the only chemical waste involved with this synthesis comes from any
necessary solvents or catalysts (scheme 1 .2).
Scheme 1.2
R (j heat
The design of atom-economic processes allows for reduction of the amount of raw materials
needed and a decrease in waste generated. Thus, designing syntheses with this principal in mind
could drastically reduce the amount of waste produced by the chemical industry while also
reducing costs.
The concept of E (environmental) factor was introduced by Roger Sheldon in 1 992 to evaluate
the environmental impact of chemical processes.6a The E factor is defined in terms of the
amount waste associated with a process and the amount of desired product produced (eq. 1 .3).
4
Equation 1.3
E fi mass oj waste produced
actor = __ ---"-__ ----0... ___ _
mass of product produced
The E factor can be determined for either an individual chemical process or an entire
industrial sector. Sheldon determined the E factors for a number of different chemical industries
(table 1 . 1 ). He found that the E factors associated with fine chemical and pharmaceutical
synthesis were relatively high when compared with more efficient industries, such as oil refining
and bulk chemical synthesis. Production of waste on such a grand scale poses a major
environmental concern and also hurts the cost effectiveness of numerous commercial processes.
Table 1.1: E Factors of Various Chemical Industries
Industry Sector Product produced (Tons) E Factor (kg waste/kg product)
Oil refining 1 06_ 108 < 0 . 1
Bulk chemicals 1 04_ 106 < 1 - 5
Fine chemicals 1 02 _ 104 5 - 50
Pharmaceuticals 1 0- 1 03 25 - 1 00
The importance of considering E factors and other Green Chemistry metrics becomes
readily apparent when considering synthetic processes that generate large amounts of waste. In
the early 1 980s, Oce Andeno closed a plant responsible for the synthesis ofphloroglucino1.6b
Phloroglucinol is used as a raw material for the synthesis of explosives and pharmaceuticals.
Closure of the plant was necessary because the cost of disposing of the waste associated with the
synthesis was approaching the profits associated with the sale of phloroglucinol. The synthetic
strategy employed at Oce Andeno involved the oxidation of 2,4,6-trinitrotoluene (TNT) with
5
potassium dichromate in fuming sulfuric acid6c (scheme 1 .3). This was followed by reduction of
the nitro substituents with iron and hydrochloric acid and an in situ decarboxylation. Heating an
acidic solution of the resulting 1 ,3,5-triaminobenzene yielded phloroglucinol.
Scheme 1.3
CH3 C02H
02N'Q'N02 K2Cr207 02N'Q'N02
Fe/ HCI 10 )110 10 )110
H2S04/ S03 N02
- CO2 N02
2,4,6-trinitrotoluene
H2NyNH2 aq. HCI
HOyOH
10 10 )110
NH2 Heat OH
phloroglucinol
The E factor for this process was determined by Sheldon to be 40. Thus, for every kg of
phloroglucinol produced, 40 kg of solid waste containing Cr2(S04h FeCh, KHS04, and NH4Cl
was generated. The cost associated with the disposal of this waste made the process impractical
and resulted in the eventual closing of the Oce Andeno plant.
Though Sheldon's E factor is a good indication of the relative amount of waste produced
by a given process or industry, the nature of the waste produced should also be taken into
account when evaluating synthetic viability. A kilogram of sodium chloride or a similarly
benign salt is not equivalent to a kilogram of a toxic compound such as a tin salt when
considering the environmental implications of chemical waste disposal. All of these factors
should be considered collectively when designing Green Chemistry processes.
6
The approach to environmentally friendly chemistry in our laboratory utilizes non-toxic
reagents that are highly catalytic in nature. It is in this context that bismuth compounds are very
attractive as catalysts and reagents in organic synthesis.
B. Bismuth Compounds
Bismuth, the 83rd element in the periodic table, has a natural abundance of 0.008 ppm in
the Earth's crust and 0.0002 ppm in sea water.7 It is a soft, crystalline metal with a whitish-pink
hue. Bismuth is the heaviest stable element and the most diamagnetic element known.
Bismuth is a remarkable element because despite its proximity on the periodic table to
toxic heavy metals such as lead and antimony, it is relative non-toxic. Due to their non-toxicity,
bismuth compounds have found numerous applications in cosmetics and medicine. For example,
the active ingredient in the anti-diarrheal medication Pepto-Bismol™ is bismuth subsalicylate
(figure 1.2). Bismuth sub citrate is the only compound known to be active against Helicobacter
pylori, a bacterium that cause ulcers.8 Bismuth sub nitrate is used in medicine as a wound
dressing and as a component in ointment for inflamed skin. Cosmetically, bismuth oxychloride
is used to impart a shimmering effect to various makeup products. Bismuth is an
environmentally friendly alternative to lead as the main component of shotgun cartridges used
for waterfowl hunting.
Figure 1.2
o �9 VO .. Bi
'OH
Bismuth Subsalicylate
7
With increasing focus on developing environmentally friendly synthesis methods,
bismuth compounds have also been used as catalysts in synthetic organic chemistry. Bismuth
compounds have several attractive features in this respect.
There is no evidence to date to suggest that bismuth compounds are carcinogenic or
mutagenic.9 The remarkable non-toxicity of bismuth compounds has earned bismuth the
distinction of a "Green" element. IO This non-toxicity is primarily due to their insolubility in
neutral aqueous solutions such as biological fluids. Bismuth compounds are poorly soluble in
the blood plasma and are readily excreted via the urinary tract. The non-toxicity of bismuth's
compounds is evident from a comparison of LD50 values for a range of common Lewis acids
(table 1 .2). As can be seen from table 1 .2, most bismuth compounds are even less toxic than
sodium chloride. Even organobismuth compounds such as triphenylbismuthine are remarkably
non-toxic.
Table 1.2: LDso Values of Bismuth Compounds and Comparable SaltslO
Compound LDso (glKg) Species and Route
Sodium Chloride, NaCl 3 . 8 Rat, Oral
Bismuth oxide, Bh03 5.0 Rat, Oral
Bismuth nitrate, Bi(N03k5H2O 4.4 Rat, Oral
Bismuth oxychloride, BiOCl 22 Rat, Oral
Triphenylbismuthine, Ph3Bi 1 80 Dog, Oral
Mercury chloride, HgCh 0.001 Rat, Oral
Cerium chloride, CeCh 2 . 1 Rat, Oral
Indium chloride, InCh 1 . 1 Rat, Oral
Samarium chloride, SmCh 2.9 Rat, Oral
Scandium chloride, ScCb 3 .9 Rat, Oral
Ytterbium chloride, YbCh 4.8 Rat, Oral
8
Despite the fact that bismuth is not common in the Earth's crust, bismuth compounds are
relatively inexpensive. This is because bismuth is a byproduct of lead, copper and tin refining.
Many bismuth(III) compounds are commercially available at a low cost (table 1 .3), which makes
bismuth compounds even more attractive as potential catalysts.
Table 1.3: Availability of Bismuth(III) Compounds and Comparable Lewis Acidsa
Compound Cost/g ($) Cost/mol ($) Bismuth chloride, BiCh 2.25 7 1 1
Bismuth nitrate, Bi(N03k5H20 0.32 1 53
Bismuth oxide, Bh03 0.49 228
Bismuth Acetate, Bi(C2H302)3 3 1097
Bismuth trifiuoromethanesulfonate, Bi(OTf)3 1 0.60 6960
Scandium trifiuoromethanesulfonate, SC(OTf)3 37 17,820
Ytterbium trifluoromethanesulfonate, Yb(OTf)3 36 22,390
Trimethylsilyltrifiate, TMSOTf 1.70 378
Titanium tetrachloride, TiCl4 0.05 9.96 aSigma-Aldrich.com
Although the hydrolysis of Bi(III) salts in water has been reported (this is discussed in
more detail later, see scheme 1 .36), bismuth compounds are relatively stable and tolerate small
amounts of air and moisture. This contrasts sharply with moisture-sensitive Lewis acid reagents
and catalysts, such as BF3·Et20 and TiC14, that must be handled under an inert atmosphere to
ensure safety and viability of the reagent.
The electron configuration of bismuth is [Xe]4/45io6i6p3 . On account of weak
shielding by the 4f electrons (Lanthanide contraction) bismuth(III) compounds exhibit Lewis
9
acidity. Thus, bismuth(III) compounds can be utilized as potential Lewis acidic catalysts for
organic synthesis.
Bismuth can also exist in the +5 oxidation state. Organobismuth compounds with
bismuth in the +5 oxidation state are known and have been applied in organic synthesis. II
Bismuth(V) compounds are commonly employed as oxidizing agents. Sodium bismuthate has
been used for the benzylic oxidation of aromatic compounds 12 (scheme 1.4).
Scheme 1.4
HOAc, Acetone, H20
Triphenylbismuth(V) dichloride has been employed as an oxidizing agent for a variety of
functionalities, including the oxidative phenylation ofphenolsl 3 (scheme 1.5).
Scheme 1.5
OH
6 R
R = electron donating
Applications of Bismuth(III) Compounds as Catalysts in Organic Synthesis
A variety ofbismuth(III) compounds have been used as Lewis acid catalysts for synthetic
transformations. 14 Bismuth(III) chloride is one of the most thoroughly investigated bismuth-
based Lewis acids. The Knoevenage1 condensationl5 (scheme 1.6), Reformatsky reactionl 6
(scheme 1.7), Die1s-Alder cyclization1 7, Mukaiyama-aldol reactionl 8 (scheme 1.8), deprotection
10
of acetals1 9 (scheme 1.9), and the allylation of acid chlorides20 (scheme 1.10) and aldehydes2 1
(scheme 1.11) have all been reported with BiCh as the catalyst.
Scheme 1.6
Scheme 1.7
Scheme 1.8
Scheme 1.9
Scheme 1.10
BiCI3 ( 1 0.0 mol %) +
R2 = CN, COOEt, CONH2, COCH3 R3 = CN, COOEt
o
Ph�Br +
BiCI3 (5.0 mol %) »
+
R' = CH3, Ph, CI
11
BiCI3, AI
BiCI3 (0.5 eq)
BiCI3 - 1 .5 Znl2
R1 R2 F< H R3
(65-78 %)
o � R �� R1 (70-92 %)
o
R�
Scheme 1.11
OH Zn or Fe BiCI3
+ R3� R1 R2 x = CI, Br, I (45 - 99 %)
Bismuth(III) bromide has been reported as a catalyst for the oxidation of epoxides to
cyclic carbonates22 (scheme 1. 12), the deprotection of alkyl TBDMS ethers23 (scheme 1. 13), the
synthesis of nucleosides24, the formation of ethers25 (scheme 1. 14), and the synthesis of
tetrahydroquinoline derivatives26 (scheme 1. 15).
Scheme 1.12
Scheme 1.13
Scheme 1.14
o Ph�
BiBr3 ( 1 0 mol %)
OSitBuMe2 �ositBuMe, _B _iB _ r.::.-3 .:..,.(3 _ m_ o_ I _%...:..., ) )loll!>-y wetCH3CN Br OSitBuMe2 �OH Br
(81 -85 %)
BiBr3 (1 -3 mol %) )10 CH3CN, rt
12
Scheme 1.15
BiBr3 (5-20 mol %)
OH
n = 1 ,2
Bismuth(III) nitrate has also received significant attention in the literature. Bismuth(III)
nitrate has been utilized as a catalyst for the oxidation of alcohols27 (scheme 1.16), the oxidation
of sulfides to sulfoxides28 (scheme 1.17), the deprotection of acetals29 (scheme 1.18) and
thioacetals30, the synthesis of acylals from aldehydes3! (scheme 1.19), and the Biginelli
reaction. 32
Scheme 1.16
Scheme 1.17
OH A R1 R2
R(S
'R2
Bi(N03h5H2O
Montmorillonite rt
Bi(N03h5H2O
CH3COOH
13
)10
]100
0 )l R1 R2
0 II
R(S
'R2 (50-85 %)
Scheme 1.18
Scheme 1.19
0
QH
I� o I�
o
Bi(N03h5H20 (0.25 eq)
EtO
Q0Et
OSitBuMe2 OSitBuMe2 76%
Bi(N03h5H20 (3-1 0 mol %) lP ROC�OCOR
(RCOhO, CH3CN Ar H
Bismuth Trifluoromethanesulfonate [Bismuth Triflate, Bi(OTf)3]
Metal triflates have received significant attention in the literature as Lewis acid
catalysts.33 Likewise, bismuth triflate is the one of the most thoroughly investigated bismuth-
based catalysts.34 Bismuth triflate is a hygroscopic white solid that exists in a hydrated form at
room temperature (Bi(OTt)3'xH20 with 1 < x < 4). Attempts to synthesize the anhydrous salt by
heating Bi(OTt)3'4H20 result in decomposition above temperatures of 100 °C.35 The final
products of this decomposition are BiF3 and H2S04. X-ray powder diffraction35 studies on
Bi(OTt)3 show that the bismuth atom is coordinated to four water molecules and four oxygen
atoms from triflate groups. It was also determined that the tetrahydrate of bismuth triflate
condenses into dimers.
Because ofthe environmentally friendly nature of bismuth salts, bismuth triflate has
received significant attention in the literature. 10, 34 Bismuth triflate has been used as a catalyst for
Diels-Alder reactions 17, 36 (scheme 1.20), Mukaiyama aldol reactions37 (scheme 1.34), Biginelli
14
reactions38 (scheme 1.21), Friedel-Crafts acylations39 (scheme 1.22) and alkylations4o, Beckmann
rearrangements4! (scheme 1.23), Michael-type reactions42 (scheme 1.24), synthesis43 and
deprotection44 of acetals, and the Sakurai allylation of a variety of functional group including
aldehydes45 (scheme 1.25), acetals46 (scheme 1.26), epoxides47 (scheme 1.27), aziridines47
(scheme 1.28), and quinones48 (scheme 1.29). This rather vast body of literature highlights the
wide applicability and versatility of bismuth triflate as a catalyst in organic synthesis.
Scheme 1.20
Scheme 1.21
x=O, S
Scheme 1.22
Bi(OTfh (0.1-10 mol %)
R1C OCI or ( R1C Oh O
Bi(OTfh (1-10 mol %)
15
Bi( OTfh
0COR1 R�
(65-96 %)
Scheme 1.23
Scheme 1.24
Scheme 1.25
Scheme 1.26
� V-{ N-OH
Polyphosphoric acid Bi(OTfb
1 00-1200C
OMe �H
o 30 %
�OMe
o
Bi(OTfb (2.0 mol %) Q �O +
+
�SnBU3
Bi(OTfb (2.0 mol %) OH
R� (65-95 %)
Bi(OTfb (1 .0 mol %) )to
CH2CI2> rt
16
MeO
96 %
OR1
R� (66-96 %)
Scheme 1.27
0
Ar�R
Scheme 1.28
Ts I N
Ar�
Scheme 1.29
0 R1VR3
I I R2
0
(�4Sn Bi(OTfb (2.0 mol %)
)100 CH2CI2, rt
(�4sn BiOTfb (2.0 mol %)
)100 CH2CI2, rt
�SiMe3
Bi(OTfb (2.0 mol %) )100
CH2CI2, rt
R
Ar� OH
(85-92 %)
C Ar �
OH R1� R2
// '-':::
OH (75-91 %)
Bismuth triflate can be synthesized in the laboratory by a variety of literature methods.
Verma and co-workers were the first to report a synthesis of bismuth triflate from bismuth(III)
trifluoracetate and triflic acid49 (scheme 1.30).
Scheme 1.30
Bi(OCOCF3b + CF3S03H (3.6 eq)
17
rt, 8 h -----l)loo1O-- Bi(OS02CF3h
Bismuth triflate has also been synthesized by treatment of triphenylbismuth with triflic acidso
(scheme 1 .3 1 ) . This method exploits the weak bismuth-carbon bonds (Bi-C bond: 1 43 KJ/mols1;
C-C bond: 447 KJ/mol) in triphenylbismuth to generate bismuth triflate. This method is not,
however, environmentally friendly because of the formation of three equivalents of benzene, a
known carcinogen.
Scheme 1.31
+ 3 TfOH -78°C
Bi(OTf)s
A greener method for the synthesis of bismuth triflate involves reaction of bismuth oxide
and triflic acid in aqueous ethanols2 (scheme 1 .32). In this procedure, bismuth triflate is isolated
by freeze-drying the solution.
Scheme 1.32
+ 6 TfOH EtOH/H20 (75125)
,., Bi(OTfb
The efficiency of bismuth triflate as a Lewis acid catalyst is especially obvious when it is
compared to other rare-earth triflates that have received considerably more attention in the
literature. Bismuth triflate is reported to be a more effective catalyst for the chlorosulfinylation
of aromatics than other triflatesS3 (scheme 1 .33) . Bismuth triflate was sucessfully employed as a
catalyst for the chlorosulfinylation of electron-rich aromatic compounds in high yields. The use
of other metal triflates, such as scandium triflate and cerium triflate, resulted in significant
amounts of sulfide byproduct 2.
1 8
Scheme 1.33
o Meo� Catalyst
1 2
Catalyst (2.0 mol %) Yield of 1 (% t Yield of2 (%t
Bi(OTf)3 99 Trace
SC(OTf)3 14 40
Ce(OTf)4 28 38
Yb(OTf)3 Trace not detected
Sb(OTf)3 75 4
a Yield determined by 1 H NMR spectroscopy
Also, bismuth triflate is a more effective catalyst for the Mukaiyama-aldol reaction37 than
other metal triflates (scheme 1 .34). I-Trimethylsilyloxycyclohexene was successfully coupled
with benzaldehyde with a low loading (1 .0 mol %) of bismuth triflate. Ytterbium(III) triflate and
yttrium(III) triflate were ineffective as catalysts for this reaction.
Scheme 1.34
Catalyst
Bi(OTf)3
SC(OTf)3
Yb(OTf)3
Y(OTf)3
aOSiMe, I +
mol %
1 .0
5 .0
5 .0
5 .0
0
uYH
0 OH Catalyst
CYD ..
CH2CI2
Temp. T Yield (%)
-70 °C 0.5 h 95
-78 °C 1 5 h 8 1
-78 °C 1 5 h trace
-78 °C 1 5 h trace
1 9
Bismuth triflate is prone to hydrolysis in water yielding triflic acid (scheme 1 .3 5). Other
rare-earth metal triflates, such as scandium triflate and lanthanum triflate are not hydrolyzed in
water. This unique property of bismuth triflate must be considered while dealing with acid-
sensitive functional groups or proposing reaction mechanisms.
Scheme 1.35
For example, Marko and coworkers have explored the role of triflic acid in the metal
triflate catalyzed acylation of alcohols54 (scheme 1 .36) . It was discovered that the rate of
benzoylation of alcohols catalyzed by bismuth triflate was greatly inhibited when the reaction
was performed in the presence 2,6-di-t-butyl-4-methylpyridine (DTBMP), a very hindered
organic base. Moreover, the reaction was successfully catalyzed using triflic acid. These data
suggest that the acylation of alcohols is actually triflic acid catalyzed. Similar observations have
been made by our group.44
Scheme 1.36
�OH
Catalyst mol % Bi(OTf)3 5 .0
Bi(OTf)3 5 .0
TfOH 8.0
DTBMP (%)
1 5 .0
o
�O)lPh
t
7 h
1 5 h
5 h a Measured by capillary GC after calibration of the response for each component
20
Conversion (%t 1 7
8
30
Bismuth triflate can also be used as a catalyst in aqueous solutions. For example, the
synthesis of2,3-disubstituted quinoxalines catalyzed by bismuth triflate in water been reported. 55
The bismuth triflate catalyzed deprotection of acyclic and cyclic acetals in aqueous THF
has also been reported44 (scheme 1 .37). This protocol also applicable to ketals and conjugated
acetals with a low loading of bismuth triflate (0. 1 - 1 .0 mol %).
Scheme 1.37
H3CXOCH3 R1 R2
0) RJ.-O
Bi(OTfh (0.1 -1 .0 mol %)
THF/H20 (80:20)
Bi(OTfh (0.1 -1 .0 mol %)
THF/H20 (80:20)
..
..
° )l R1 R2
° R)lH
Many reagents and catalysts are destroyed when exposed to small amounts of water.
This makes the use of anhydrous solvents and reagents imperative in many cases. Catalysts and
reagents must often be handled under an inert atmosphere. In contrast, most reactions catalyzed
by bismuth triflate do not require dry solvents or inert atmosphere conditions.
The environmentally friendly nature of bismuth (III) triflate coupled with its ease of
handling and inexpensive nature have prompted us to explore its utility as a catalyst for a variety
of synthetic transformations.
C. Literature Review: Allylation of Acetals
Hosomi-Sakurai Allylation of Acyclic Acetals
Some of most important organic transformations involve the formation of carbon-carbon
bonds. These methodologies are especially important in the synthesis of pharmaceuticals and
21
natural products. Methods that have been developed for the formation of carbon-carbon bonds
include the Suzuki Cross-Coupling56, Friedel-Crafts acylation57 and alkylation58, the Michael
reaction59, Olefin Metathesis6o, and Diels-Alder cyclization.61 The nucleophilic allylation of
various carbon electrophiles is also an efficient strategy for carbon-carbon bond formation. The
Hosomi-Sakurai reaction involves the Lewis or protic acid catalyzed allylation of various
electrophiles using allyl silanes. This method is commonly regarded as a mild method for
carbon-carbon bond formation. Hosomi and Sakurai first reported the TiCl4-promoted allylation
of aldehydes and ketones to yield homoallyl alcohols62 (scheme 1.38).
Scheme 1.38
TiCI4 (0.5 eq)
They also successfully extended this methodology to the allylation of acyclic acetals63 (scheme
1.39). This represents an efficient synthesis of homo allyl ethers from readily available acetal
starting materials. Following their report, the allylation of acyclic acetals to yield homo allyl
ethers has since been well studied with a number of different Lewis acid catalysts. These include
diphenylboryl triflate68, bis(fluorosulfonyl)imide69, montmorillonite 70, CuBr7\ tris(p-
bromophenyl)aminium hexachloroantimonate72, Sc(OTf)3 73 , and BiBr3 .74 Many of the catalysts
previously employed for this synthesis are corrosive, for example AICl], TiC14, and TMSOTf, or
toxic, for example BF3"Et20. Additionally, stoichiometric catalyst loadings are often necessary.
Low temperatures and anhydrous conditions are also required in several of these reported
22
protocols. These conditions detract from the utility of these procedures in the industry because
of environmental and safety concerns.
Scheme 1.39
Our group has reported the bismuth(III) triflate-catalyzed allylation of acyclic acetals and
ketals to yield homoallyl ethers in good yields75 (scheme 1 .40). The allylation reactions
proceeded smoothly at room temperature with a low catalyst loading (1 .0 mol %).
Scheme 1.40
Bi(OTf)s (1.0 mol %) ..
This procedure provides a highly catalytic and environmentally friendly route to
homoallyl ethers compared to previously reported methodologies.
Hosomi-Sakurai Allylation of Aldehydes
In contrast to the allylation of acyclic acetals, the allylation of aldehydes and carbonyl
compounds to yield homoallyl ethers has received relatively little attention in the literature.
Sakurai and co-workers reported the allylation of aldehydes and ketones catalyzed by
iodotrimethylsilane in the presence of alkoxysilanes to yield homo allyl ethers 76 (scheme 1 .4 1 ) .
Trimethylsilyl triflate has also been used as a catalyst for the allylation of aldehydes in the
23
presence of alkoxysilanes to yield benzyl homo allyl ethers and n-hexyl homoallyl ethers.77 Two
disadvantages of this method are the utilization of a corrosive catalyst and the use of carbon
tetrachloride, a carcinogenic and environmentally harmful solvent.
Scheme 1.41
M e3Si I (10.0 mol %) �
We have recently reported the iron(III) p-toluenesulfonate catalyzed allylation of
aldehydes and acetals to yield homoallyl ethers78 (scheme 1 .42) . The direct conversion of
aldehydes to the corresponding homo allyl ether is advantageous because few acetals are
commercially available and must be typically synthesized from the corresponding aldehyde. In
addition, many acetals have a poor shelf life due to their acid-sensitive nature. Moreover, most
methods in the literature for the allylation of acetals only report the synthesis of homo allyl
methyl or ethyl ethers. These compounds are not very amenable to further synthetic
manipulation since the alkyl group appended to the homo allyl ether oxygen is an inert methyl or
ethyl group. A one-pot procedure utilizing alkoxysilanes allows for the installation of functional
groups that are more amenable to further synthetic manipulation. This is possible because a wide
range of alkoxysilanes is commercially available including benzyloxytrimethylsilane,
ethoxytrimethylsilane, and allyloxytrimethylsilane.
24
Scheme 1.42
o
R(,llH �SiMe3
Fe(OTsh6H20 CH3CN, rt
We reported the allylation of aldehydes and ketones under mild conditions to yield
homo allyl methyl ethers, homo allyl ethyl ethers, homoallyl allyl ethers, and homoallyl benzyl
ethers. This protocol was applicable to both aliphatic and aryl aldehydes with low catalyst
loadings ( 1 .0- 1 0.0 mol %). This method is especially attractive because ofthe utilization of
iron(III) tosylate, an inexpensive and non-corrosive Lewis acid catalyst.
Our group has also reported the one-pot synthesis of homo allyl ethers from aldehydes
catalyzed by bismuth(III) triflate79 (scheme 1 .43). Trialkylorthoforrnates or alkoxysilanes were
employed to generate acetals or oxenium ions respectively, which can then undergo allylation to
yield homoallyl ethers.
Scheme 1.43
HC(OR1b or R10SiMe3
�SiMe3
Bi(OTfb (0.1-5.0 mol %) CH3CN or CH2CI2 27-82 %
This methodology was applicable to a variety of aryl aldehydes with a low catalyst loading. The
use of alkoxytrimethylsilanes is particularly attractive because it allows for the installation of
synthetically useful allyl or benzyl groups at the homo allyl ether oxygen.
25
The one-pot synthesis of homo allyl acetates from aldehydes catalyzed by bismuth triflate has
also been reported (scheme 1 .44). This procedure utilized acetic anhydride to generate the
corresponding acylals, which can then undergo allylation to yield homo allyl acetates. Aldehydes
with strongly electron-donating groups (p-methoxy) underwent diallylation under the reaction
conditions. The use of a relatively non-corrosive and non-toxic catalyst coupled with the wide
availability of aldehydes makes this an attractive route to homo allyl acetates
Scheme 1.44
(CH3COhO
�SiMe3
Bi(OTf)s (1.0 mol %)
CH3CN
OAe
R� 57-66 %
Hosomi-Sakurai Allylation of 1,3-Dioxolanes and 1,3-Dioxanes
Dioxolanes and dioxanes (fig. 1 .3 ) have been primarily utilized as acid-labile protecting
groups in organic synthesis. 80
Figure 1.3
1,3-dioxolane 1,3-dioxane
However, cyclic acetals can also be converted to other useful functional groups in the course of a
synthesis. For example, the synthesis of hydroxy esters by oxidation of cyclic acetals with m-
chloroperbenzoic acid has been reported8 1 (scheme 1 .45).
26
Scheme 1.45
R2�R3
°XO
R1 H n
= 0, 1
BF3·Et20 (10 mol %) mCPBA (1 eq) ° R2 R3 --b -en- z- e-n -e,- rt----i· .... R(1l0�OH
Cyclic acetals have received very little attention in the literature as substrates in the Hosomi-
Sakurai reaction. Nevertheless, the ring-opening allylation of cyclic acetals ought to lead to the
synthesis of highly functionalized alcohols (scheme 1 .46).
Scheme 1.46
�SiMe3 . _-------------- .....
Lewis Acid
Kuwajima and co-workers reported the allylation of a substituted 1 ,3 -dioxolane catalyzed
by TiCI4, AICh, and SnC14.82 They found that the regioselectivity of ring-opening of a 4,4-
dimethyl substituted 1 ,3-dioxolane was dependent on the Lewis acid used and the order of
addition of reagents (scheme 1 .47). When TiC14 was employed as the Lewis acid,
regioselectivity was dependent on the order of addition of allyltrimethylsilane and TiC14. When
AICh and SnC14 were used, isomer 4 was the major product ( 1 :99, 3:4). They also reported that
the allylation did not proceed with TMSOTf as the catalyst and allyltrimethylsilane as the allyl
source. Instead, allyltributyltin, a highly toxic organotin reagent, was necessary to afford the
desired allylated product under these conditions.
27
Scheme 1.47
Lewis Acid
O�OH
C6H13--Z� �SiMe3 O�OH
C6H13� + C6H13� )Po
CH2CI2 3 4
Mead and co-workers have reported the allylation of spiroketals using BF3'EhO, TiC14,
and TMSOTf as Lewis acid catalysts83 (scheme 1 .48). Stoichiometric catalyst loadings and low
temperature conditions were necessary to promote the reaction. A mixture ofmonoallylated (5)
and diallylated (6) products was obtained in most cases. Because of these factors, this procedure
is not very attractive within the context of Green Chemistry.
Scheme 1.48
�SiMe3
TMSOTf, TiCI4, or BF3'OEt2
The allylation of a cyclic acetal derived from �-D-ribo-hexopyranose has been reported84
(scheme 1 .49) . The allylation required stoichiometric loadings of both TMSOTf (3 eq) and
BF3'EhO (3 eq) with allyltrimethylsilane (1 2.3 eq) as the allylating agent. Moreover, the
allylation yielded a mixture of isomers, only one of which, 7, was carried on in the synthesis.
28
Scheme 1.49
7:8=10 :1
Morelli and co-workers have reported the TiCl4 promoted allylation of 4-trifluoromethyl-
1 ,3-dioxolanes85 (scheme 1 .50). This protocol was extended to only three aliphatic dioxolanes.
Furthermore, highly toxic allyltributyltin was used as the source of the allyl group and a
stoichiometric loading of TiCl4 was necessary to afford the desired homo allyl ether product.
Scheme 1.50
CF3
J�Me R 0
TiCI4
�SnBu3
CH2CI2• OoC 1 5 m in
Me)--(CF3
o OH
.. R� 62% - 85%
The allylation of 1 ,3-dioxolanes catalyzed by Sn(OTf)2 in the presence of alkoxysilanes
has been reported86 (scheme 1 .5 1 ). This synthesis yielded homo allyl ethers as a result of
exchange between the alkoxysilane and the 1 ,3-dioxolane. The authors propose that the
allylation of the acyclic acetal resulting from the exchange is faster than the allylation of the
cyclic acetal. This reaction was applicable to a number of aliphatic and aryl dioxolanes in good
yields, but a stoichiometric catalyst loading was necessary.
29
Scheme 1.51
�SiMe3 ( 1 .4 eq) R30SiMe3 (2.0 eq)
Sn(OTfh (1.0 eq) CH3CN, -20 DC
exchange
)10 OR3
R1� 41 -97%
fast OR3
R1� observed product
The allylation of a number of 1 ,3-dioxolanes and 1 ,3-dioxanes catalyzed by TMSOTfhas
been reported by Hunter and co-workers87 (scheme 1 .52). This method utilized allyl borates as
the source of the allyl group. The allyl borate reagents are not commercially available and must
be synthesized in lab. A corrosive catalyst (TMSOTf) was employed in stoichiometric quantities
and low temperature conditions were required (-78 °C). In a few cases, an alcohol byproduct
arising from reduction of the cyclic acetal under the reaction conditions was also isolated in
significant yield.
Scheme 1.52
n = 1 , 2 TMSOTf ( 1 .2 eq)
THF, -78 DC to 0 DC
+
38-71 % reduction product
Denmark and co-workers have reported one of the few Sakurai-Hosomi protocols utilizing 1 ,3 -
dioxanes as substrates88 (scheme 1 .53). The allylation of 4,6-dimethyl-2-hexyl-l ,3-dioxane
proceeded with a high degree of diastereoselectivity (270: 1 ) with a stoichiometric loading of
TiCLJTi(O-i-Pr)4 ( 1 1 eq) and allyltributyltin (8 eq) as the allylating agent. The
30
diastereoselectivity was much lower when allyltrimethylsilane was employed (56: 1 ). The use of
a corrosive Ti-based catalyst and a toxic organotin compound in superstoichiometric amounts
detracts from the utility of this method.
Scheme 1.53
�SnBU3 (8 eq)
TiCI41Ti(O-i-Pr)4 (11 eq)
CH2CI2 -78 QC
�SiMe3 (8 eq)
TiCI41Ti(O-i-Pr)4 (11 eq) CH2CI2 -78 QC
QH3 CH3
O�OH
n-C6H13� 9
+
100% dr 9/10 = 270/1
+
100% dr 9/10 = 56/1
QH3 CH3
9�OH
n-C6H13�
The lack of a highly catalytic, widely applicable, and environmentally-friendly method
for the allylation of cyclic acetals prompted us to explore the bismuth(III) triflate-catalyzed
allylation of cyclic acetals. The development of greener methods for allylation chemistry is of
particular relevance because of increasing environmental concerns and the importance of carbon-
carbon bond forming reactions in organic synthesis. Bismuth-based Lewis acids are particularly
attractive in this respect because they are relatively non-toxic, non-corrosive, and inexpensive.
3 1
II. Results and Discussion
A. Allylation of 1 ,3-Dioxolanes followed by in situ Derivitization with Acid Anhydrides
Catalyzed by Bismuth(III) Triflate
The lack of a highly catalytic and environmentally benign method for the ring-opening
allylation of 1 ,3-dioxolanes (scheme 2 . 1 ) prompted our interest in investigating the utility of
bismuth(III) triflate as a catalyst for this transformation. In contrast to the Hosomi-Sakurai
allylation of aldehydes62, 76-79 and acyclic acetals63-7S, the allylation of cyclic acetals has received
very little attention.
Scheme 2.1
�x
Catalyst
Solvent
Bismuth triflate was not an effective catalyst for the allylation of 1 ,3-dioxolanes to yield
the expected alcohol products (scheme 2.2) . Instead, a mixture of starting material and the
corresponding aldehyde was isolated.
Scheme 2.2
Bi(OTfh
were isolated
32
It was reasoned that one way to push the reaction might be to trap the putative alkoxide
intermediate that results from addition of the allyl group with an electrophile (scheme 2.3) . This
method would represent a multi component reaction in which the alkoxide is derivatized in a one-
pot process.
Scheme 2.3
�SiM e3
Bi(OTf )3
Solvent
O�OE
R� ' R�
Attempts to capture the alkoxide with trimethylsilylchloride or p-toluenesulfonic anhydride were
unsuccessful (scheme 2.4). In both cases, a mixture of starting material and aldehyde was
obtained.
Scheme 2.4
TMSCI (1 .2 eq) O�OTMS
�SiMe3 ( 1 .2 eq) I ----------------�.� Ph�
Bi(OTf)s (2.0 mol %)
Ts20 ( 1 .7 eq)
�SiMe3 ( 1 .7 eq) 0 Bi(OTf)s (2.0 mol %) 7 ,.
CH3CN
work-up / / /7.
Gratifyingly, we were able to trap the alkoxide intermediate with acetic anhydride
(scheme 2 .5), a protocol that allowed for the synthesis of highly functionalized esters in a one-
33
pot process. There are no literature reports for the allylation of cyclic acetals involving an in situ
derivatization of the alkoxide, and thus, this new procedure is especially attractive. Such
multi component reactions reduce the time and number of steps associated with a synthesis
because isolation of intermediates is unnecessary.
Scheme 2.5
AC20 ( 1 .7x)
�SiMe3 ( 1 .7x)
B i (OTfb (2.0 mol %)
CH3C N, 0 °C
o�Oy Ph�O
An efficient one-pot procedure for the synthesis of highly functionalized ester products was thus
developed.89 The protocol was applied to the allylation of a number of aryl and aliphatic
dioxolanes (table 2 . 1 ).
Although the initial work was performed using acetonitrile as the solvent, the reactions
were also found to proceed smoothly under solvent-free conditions. This reduces the amount of
waste associated with the reaction. Products were initially isolated by aqueous work-up followed
by filtration through a silica column. The unacceptably low purity of crude products and the
difficulty of removing anhydrides during work-up prompted us to consider a direct filtration of
the reaction mixture through a silica gel column. This simple purification eliminates the need for
a tedious aqueous work-up and reduces the total amount of organic waste associated with the
synthesis.
34
Table 2.1: Bismuth(III) Triflate Catalyzed Allylation of 1,3-Dioxolanes
O�OCOR2
2.0 mol % Bi(OTfb I .. R 1
� �SiMe3 (1.7x)
(R2COhO (1. 7x) o DC
RI R2 t Yield (%)
p-CIC6H4 Me 40 min 67a
p-CH3C6H4 Me 1 h 43b
o-BrC6H4 Me 1 h 62b,c
o-FC6H4 Me 1 h 6 1 b
m-BrC6H4 Me 45 min 73b
CH3(CH2)8 Me 21 h 30 min 73b,c
p-CIC6H4 iPr 35 min 36a
O-BrC6H4 iPr 4 h 30 min 47a
o-CIC6H4 iPr Ih 1 5 min 53a
CH3(CH2)8 iPr 3 h 35 min 44a
O-BrC6H4 tBu 2 h 40 min 54a
a Reaction mixture was loaded onto silica gel and eluted with EtOAc/ heptane
b Product was isolated by aqueous work-up followed by flash chromatography
c Reaction carried out in CH3CN at rt
This transformation was successful with a low catalyst loading (2.0 mol %) and under
mild, solvent-free reaction conditions. This contrasts sharply with previous reports in which
stoichiometric loadings of corrosive catalysts (TiC14, TMSOTf, SnCI4) were necessary to
35
promote allylation. Reaction times were relatively short ( 1 -4 h), with the exception of aliphatic
dioxolanes which required longer reaction times. All reactions proceeded at 0 0 C and under
mild, solvent-free conditions. Many methods reported to date require low temperature
conditions (-78 0 C).
Moreover, many of the previous procedures were only applied to a few dioxolanes. Our protocol
was amenable to a variety of aliphatic and substituted aryl dioxolanes. Electron-rich aryl
dioxolanes underwent allylation with a low catalyst loading (2.0 mol %).
A variety of acid anhydrides such as acetic anhydride, isobutyric anhydride and
trimethylacetic anhydride were successfully employed for the in situ derivatization of the
alkoxide intermediate. However, the yield of the product dropped with use of hindered
anhydrides. Thus, structural diversity can be introduced into the ester product by altering both
the dioxolane and acid anhydride utilized. Furthermore, the highly functionalized product is
formed via a one-pot procedure from commercially available or readily accessible dioxolane
starting materials.
Attempts to apply the protocol to the allylation of 1 ,3 -dioxolanes derived from ketones
were unsuccessful. A mixture of starting material and acetophenone was isolated when the 1 ,3 -
dioxolane derived from acetophenone was subjected to the established reaction conditions
(scheme 2.6).
36
Scheme 2.6
�SiMe3 ( 1 .7 eq)
AC20 ( 1 .7 eq)
Bi(OTfh (2.0 mol %) o De
/
B. Mechanistic Studies on the Bismuth(IH) Triflate-Catalyzed Allylation of Dioxolanes
In order to determine the mechanism by which bismuth(III) triflate is catalyzing the
allylation of dioxolanes, a number of control experiments were performed (scheme 2.7). Though
it was hypothesized that bismuth triflate is acting as a Lewis acid, it is also possible that the
reaction is protic acid catalyzed. Triflic acid generated in solution by the hydrolysis of bismuth
triflate could potentially be catalyzing the allylation of dioxolanes.
As was already established, the allylation of 2-(2-bromophenyl)-1 ,3-dioxolane catalyzed
by bismuth triflate (2.0 mol %) proceeded to completion in an hour. The allylation does not
proceed in the absence of a catalyst. When triflic acid (5.0 mol %) was used as a catalyst for the
allylation, a mixture of desired product and aldehyde was detected by GC analysis of the reaction
mixture.
The bismuth triflate-catalyzed allylation was also conducted in the presence of 1 ,8-
(dimethylamino)napthalene (Proton Sponge™)90 (figure 2. 1 ).
37
Figure 2.1
(CH�H3)'
VU Proton Sponge ™
1 ,8-bis( dimethylamino )napthalene
Under these conditions, no product or aldehyde was observed by GC. While this might suggest
that the reaction is protic acid catalyzed, it is also possible that the amino functionalities of 1 ,8-
(dimethyl amino )napthalene are strongly coordinating to bismuth triflate, rendering it unable to
catalyze the reaction. More studies are necessary to determine bismuth triflate's role in
catalyzing the allylation of dioxolanes.
Scheme 2.7
o� �o Vsr
�SiMe3 ( 1 .7x)
AC20 ( 1 .7x)
2.0 mol % Bi(OTfb
No Catalyst
2.0 mol % Bi(OTfb
7 mol % proton sponge
38
o� o� II 1 h, 90% product by GC
O-BrC6H4� 0
No product
1 h, 40% product, 55% aldehyde by GC
No product
A proposed mechanism for allylation involving activation of the dioxolane by bismuth
triflate is shown (scheme 2.8).
Scheme 2.8
RJ....) + Bi(OTfh
. . � 1
° �oSiMe3
+ Bi(OTfh +
.k,.> Tf0 8 R )0'" . <±> BI(OTf)2
�SiMe3 2
+ TfOSiMe3
/'... .0- Bi(OTfh O� ......" • •
------�.� R� 3
C. Allylation of 1,3-Dioxanes followed by in situ Derivitization with Acid Anhydrides
Catalyzed by Bismuth(III) Triflate
When compared to the allylation of 1 ,3-dioxolanes, there is very little precedent for the
allylation of 1 ,3-dioxanes in the literature. Furthermore, the established methods utilize
stoichiometric quantities of corrosive catalysts (TiCI4/Ti(O-i-Pr)4 or TMSOTf). Hunter and
coworkers utilized allyl borates as the source of the allyl group87 (scheme 1 .52). These
compounds must be prepared in lab, detracting from the utility of this procedure. Denmark and
coworkers utilized a large excess (8 eq) of allyltrimethylsilane or the highly toxic
allyltributylstannane as the allyl source88 (scheme 1 .53). Thus, our goal was to apply the
previously developed allylation methodology to the allylation of 1 ,3-dioxanes. This would
constitute the first catalytic allylation of 1 ,3 -dioxanes reported in the literature.
39
The previously developed procedure was applied to the allylation of a number of aryl and
aliphatic 1 ,3-dioxanes (table 2.2). Though the acetal center is more electron-rich in dioxanes
than dioxolanes as supported by J 3C NMR data, the allylations all proceeded to completion with
a low catalyst loading (2.0 mol %). In all cases, acetic anhydride was used to derivatize the
alkoxides in situ. The resulting functionalized esters were isolated in moderate to good yields.
Table 2.2: Bismuth(III) Triflate Catalyzed Allylation of 1, 3-Dioxanes
0
R,1) 2.0 mol % Bi(OTf)s O�O)lGH3 .. R1� �SiMe3 ( 1 .7x)
(GH3GObO (1 .7x)
O DG R t Yielda (%)
O-BrC6H4 1 h 30 min 79
p-BrC6H4 2 h 65
p-CIC6H4 2 h 70
p-CH3C6H4 1 h 30 min 60
m-CH3OC6H4 1 h 30 min 70
CH3(CH2)s 4 h 75
BrCH2CH2 2 h 30 min 70
a Reaction mixture was loaded onto silica gel and eluted with EtOAcl heptane
The allylation of 5 ,5-dimethyl substituted 1 ,3-dioxanes was also explored using the
developed conditions. The allylation and in situ derivatization of aryl and aliphatic 5 ,5-
dimethyl- l ,3-dioxanes was successful under mild conditions (table 2.3). The ester products were
isolated in moderate to good yields in all cases.
40
Table 2.3: Bismuth(III) Triflate Catalyzed Allylation of 5, 5-Dimethyl -l, 3-Dioxanes
o
2.0 mol % Bi(OTfb O�O)lCH3
-------!>-I> R1� �SiMe3 (1 .7x)
R
p-CIC6H4
p-CH3C6H4
CH3(CH2)s
(CH3CObO ( 1 .7x)
O DC
t
1 0 min
30 min
3 h 30 min
Yield (%)
a Reaction mixture was loaded onto silica gel and eluted with EtOAcI heptane. b Product was
isolated by aqueous work-up followed by flash chromatography.
D. AUylation of 1,3-Dithianes followed by in situ Derivitization with Acid Anhydrides
Catalyzed by Bismuth(III) Triflate
1 ,3-Dithianes have received significant attention in the literature as protecting groups for
carbonyl compounds.80 Also, their application in the "Umpolung" chemistry pioneered by
Seebach and Corey is well precedented91 (scheme 2.9).
Scheme 2.9
n-BuLi
THF, - 30 DC
41
Dithianes can be also be potentially converted to other useful functional groups. To date,
there has been no report of a Hosomi-Sakurai type allylation of dithianes to yield functionalized
thiols (scheme 2. 1 0) .
Scheme 2.10
Lewis Acid Solvent
S�SH
R�
This total lack of literature precedent for the allylation of 1 ,3-dithianes prompted our interest in
extending the established bismuth(III) triflate catalyzed allylation methodology to this
functionality. A one-pot allylation and in situ derivatization of 1 ,3-dithianes with acid
anhydrides would constitute an efficient synthesis of functionalized thioesters (scheme 2. 1 1 ) .
Scheme 2.11
�SiMe3 ( 1 .7 eq)
(CH3COhO ( 1 .7 eq)
Bi(OTfh (2.0 mol %)
O OC
Initial attempts to allylate 2-( 4-chlorophenyl)-1 ,3-dithiane to yield the corresponding
functionalized thiol were unsuccessful (scheme 2. 12). GC analysis of the reaction mixture
indicated that no reaction was taking place.
42
Scheme 2.12
�SiMe3 ( 1 .7 eq)
Bi(OTfh ( 1 0 mol %)
CH3CN, O OC
7
However, by using a protocol similar to the allylation of dioxolanes and dioxanes, the
thiolate intermediate was successfully trapped with acetic anhydride to yield the corresponding
thioester. This strategy was applied to a handful of aryl and aliphatic dithianes, yielding the
corresponding thioesters in moderate to good yields (table 2.4).
Table 2.4: Bismuth(III) Triflate Catalyzed Allylation of 1,3-Dithianes
�SiMe3 ( 1 .7 eq) 0
RJ) (CH3CO)20 ( 1 .7 eq) S�SJl.CH3 ..
R� Bi(OTfh
O OC
R mol % Bi(OTf)3 t Yieldb (%)
C6HS 2.0a 3 h 45 min 78
p-CIC6H4 2.0 2 h 45 min 65
m-CH3C6H4 4.0 4 h 30 min 74
CH3(CH2)8 1 0.0 3 h 30 min 63
a An additional 2.0 mol % Bi(OTf)3 was added after 3 h. b Reaction mixture was loaded onto
silica gel and eluted with EtOAc/ heptane.
The allylation of 1 ,3-dithianes proceeded smoothly under mild, solvent-free conditions with low
catalyst loadings (2.0 -1 0.0 mol %). Although allylation of dioxolanes and dioxanes proceeded
43
with a 2.0 mol % loading of bismuth (III) trifiate, electron-rich aryl dithianes and aliphatic
dithianes required more catalyst (4.0 - 1 0.0 mol %) for the reactions to proceed to completion.
To the best of our knowledge, this procedure represents the first example ofthe
application of 1 ,3-dithianes as substrates for the Hosomi-Sakurai reaction. Furthermore, the
method utilizes a non-toxic and non-corrosive catalyst and solvent-free conditions.
Conclusions
A robust and highly catalytic method for the allylation and in situ derivatization of a
number of cyclic acetals (dioxolanes, dioxanes, and dithianes) has been developed. There has
been little precedent in the literature for the allylation of these functionalities. Most reagents
used to date for the allylation of cyclic acetals are highly corrosive or toxic and are often
required in stoichiometric amounts. In contrast, the use of a relatively non-toxic and non
corrosive bismuth(III) based catalyst and the lack of an aqueous waste stream make the
developed methodology environmentally benign and attractive.
44
III. Experimental
A. General Experimental:
Bismuth(III) triflate was purchased from Aldrich Chemical Company and stored under vacuum.
Allyltrimethylsilane was purchased from Acros Chemical Company or Aldrich Chemical
Company. Acetic anhydride was purchased from Fisher Scientific. Dioxanes and dithianes were
prepared in lab following procedures developed in our group or literature protocols.80 Products
were analyzed using a lEOL Eclipse NMR Spectrometer at 270 MHz for lH NMR and 67.5
MHz for I 3C NMR in CDCb as the solvent. GC analysis was performed on a Varian CP-3800
Gas Chromatograph equipped with a 30 m silica-packed column with a diameter of 0.25 mm
(Conditions: hold at 1 00 °C for 1 min; ramp at 30 °C/min until 220 °c ; hold at 220 °C; flow rate;
2 .0 mL/min of He). Thin-layer Chromatography was performed on alumina backed silica gel
plates. Spots were visualized under UV light (when a UV active chromophore was present) and
by spraying the plate with phosphomolybdic acid followed by heating. Purifications were
performed by flash chromatography on silica gel.92 Products were characterized by lH NMR,
I 3C NMR, and GC. Satisfactory elemental analysis or High Resolution Mass Spectrometry
(HRMS) data was obtained for all new compounds.
45
B. Bismuth(III) Triflate Catalyzed Allylation of 1,3-Dioxanes
Allylation of 2-(2-bromophenyl)-1,3-dioxane (MJS2057fr2051)
�SiMe3 (1 .7 eq)
AC20 ( 1 .7 eq)
2.0 mol % Bi(OTf)s D oC
o O�O� � UO� Br
A homogeneous mixture of 2-(2-bromophenyl)-1 ,3-dioxane (0.2450 g, 1 .008 mmol),
allyltrimethylsilane (0.2723 mL, 0. 1958 g, 1 .7 1 3 mmol, 1 .7 eq), and acetic anhydride (0. 1 620
mL, 0. 1 749 g, 1 .7 1 3 mmol, 1 .7 eq) was stirred at 0 °C under N2 in a flame-dried three-neck rbf
as bismuth(III) triflate (0.0132 g, 0.0202 mmol, 2.0 mol %) was added. The reaction mixture
immediately acquired a light yellow color. Reaction progress was followed by gas
chromatography. After 1 h 30 min, the reaction mixture was loaded onto 65 g of silica gel and
eluted with EtOAc/heptane (5/95, v/v). Fifty-eight fractions (8 mL) were collected after a 1 00
mL prefraction. Fractions 20 to 5 1 were combined and concentrated to yield 0.26 g (79 %) of a
clear, colorless liquid product that was determined to be 97 % pure by GC analysis and IH & l 3C
NMR spectroscopy. IH NMR: () 1 .84- 1 .89 (m, 2 H), 1 .99 (s, 3 H), 2.39-2.44 (m, 2 H), 3 .34-3 .38
(m, 2 H), 4. 1 3-4. 1 8 (t, 2 H, J= 6.43 Hz), 4.68-4.71 (m, 1 H), 5 .00-5 .07 (m, 2 H), 5 .80-5 .86 (m, 1
H). 7. 1 0-7.5 1 (m, 4 H). l 3C: ( 1 5 peaks) () 1 7 1 .0, 141 .2, 1 34.4 1 32.6, 128.7, 1 27.6, 1 27.6, 1 22.9,
1 1 7.0, 80.2, 65 .4, 6 1 .6, 4 1 . 1 , 28.9, 20.9. HRMS-EI (mlz) : M+ calcd for Cl sHI9Br03Na,
349.04 1 5 ; found, 349.0423 .
46
Allylation of 2-( 4-bromophenyl)-1,3-dioxane (MJSl 185fr5069)
�SiMe3 ( 1 .7 eq)
AC20 ( 1 .7 eq)
2.0 mol % Bi(OTf)s D oC
A homogenous mixture of 2-(4-bromophenyl)- 1 ,3-dioxane (0.2501 g, 1 .029 mmol),
allyltrimethylsilane (0.2779 mL, 0. 1 998 g, 1 .749 mmol, 1 .7 eq), and acetic anhydride (0. 1 653
mL, 0 . 1 785 g, 1 .749 mmol, 1 .7 eq) was stirred at 0 °C under N2 in a flame-dried three-neck rbf
as bismuth(III) triflate (0.01 3 5 g, 0.0206 mmol, 2.0 mol %) was added. The reaction mixture
immediately acquired a light yellow color. Reaction progress was followed by gas
chromatography. After 2 h, the reaction mixture was loaded onto 65 g of silica gel and eluted
with EtOAc/ heptane (5/95, v/v). Seventy-two fractions (8 mL) were collected after a 1 00 mL
prefraction. Fractions 50 to 69 were combined and concentrated to yield 0.22 g (65 %) of a
clear, colorless liquid product that was determined to be 98 % pure by GC analysis and IH & 1 3C
NMR spectroscopy. IH NMR: () 1 .82- 1 .86 (m, 2 H), 1 .98 (s, 3 H), 2.32-2.50 (m, 2 H), 3 .3 1 -3 .34
(m, 2 H), 4. 1 0-4. 1 5 (m, 3 H), 4.96-5.02 (m, 1 H), 5.65-5.76 (m, 1 H), 7. 1 1 -7. 1 4 (d, 2 H, J = 8. 1 5
Hz), 7.42-7.45 (d, 2 H, J = 8 . 1 5 Hz). 13C: ( 1 3 peaks) () 1 7 1 .0, 141 . 1 , 1 34.2, 1 3 1 .4, 1 28 .3 , 1 2 1 .3 ,
1 1 7 .2, 8 1 .5 , 65.0, 6 1 .6, 42.4, 28.9, 20.9. HRMS-EI (mlz): M+ calcd for CI SHI 9Br03Na,
349.04 1 5 ; found, 349.04 17.
47
AHylation of 2-( 4-chlorophenyl)-1,3-dioxane (MJS 1179fr8099)
�SiMe3 ( 1 .7 eq)
AC20 (1 .7 eq)
2.0 mol % Bi(OTf)s O OC
A homogenous mixture of 2-(4-chlorophenyl)- 1 ,3-dioxane (0.2500 g, 1 .259 mmol) ,
allyltrimethylsilane (0.3399 mL, 0.2445 g, 2. 140 mmol, 1 .7 eq), and acetic anhydride (0.2022
mL, 0 .2 1 84 g, 2 . 140 mmol, 1 .7 eq) was stirred at 0 °C under N2 in a flame-dried three-neck rbf
as bismuth(III) triflate (0.01 65 g, 0.0252 mmol, 2.0 mol %) was added. The reaction mixture
immediately acquired a light yellow color. Reaction progress was followed by gas
chromatography. After 2 h, the reaction mixture was loaded onto 66 g of silica gel and eluted
with EtOAc/heptane (5/95, v/v). One hundred and six fractions (4 mL) were collected.
Fractions 80 to 99 were combined and concentrated to yield 0.25 g (70 %) of a clear, colorless
liquid product that was determined to be 98 % pure by GC analysis and IH & 1 3C spectroscopy.
IH NMR : 0 1 . 82- 1 .89 (m, 2 H), 1 .98 (s, 3 H), 2.32-2.54 (m, 2 H), 3 .3 1 -3 .34 (m, 2 H), 4. 1 1 -4.20
(m, 3 H), 4.97-5 .03 (m, 2 H), 5 .66-5 .76 (m, 1 H), 7 . 1 7-7.3 1 (m, 4 H). 13C: ( 1 3 peaks) 0 1 7 1 .0,
1 40.6, 1 34.2, 1 3 3 . 1 , 1 28.4, 128.0, 1 1 7.2, 8 1 .4, 65.0, 61 .5, 42.4, 28.9, 20.9. HRMS-EI (mlz) : M+
calcd for ClsHI9CI03Na, 305 .0920; found, 305.09 13 .
48
Allylation of 2-( 4-tolyl)-1,3-dioxane (MJS2051fr3052)
o �SiMe3 (1 .7 eq) O�O�
AC20 ( 1 .7 eq)
~ ----...... I � � 2.0 mol % Bi (OTf)s
H3C h-O OC
A homogenous mixture of 2-(4-tolyl)- 1 ,3-dioxane (0.2497 g, 1 .402 mmol), allyltrimethylsilane
(0.3788 mL, 0.2723 g, 2.383 mmol, 1 . 7 eq), and acetic anhydride (0.2253 mL, 0.2433 g, 2 .383
mmol, 1 .7 eq) was stirred at 0 °C under N2 in a flame-dried three-neck rbf as bismuth(III) triflate
(0.0 1 84 g, 0.0280 mmol, 2.0 mol %) was added. The reaction mixture immediately acquired a
bright pink color. Reaction progress was followed by gas chromatography. After 1 h 30 min,
the reaction mixture was loaded onto 60 g of silica gel and eluted with EtOAc/heptane (5/95,
v/v). Sixty fractions (8 mL) were collected. Fractions 30 to 52 were combined and concentrated
to yield 0.22 g (60 %) of a clear, colorless liquid product that was determined to be 99 % pure by
GC analysis and IH & l 3C spectroscopy. IH NMR: 0 1 .82- 1 .89 (m, 2 H), 1 .98 (s, 3 H), 2.33 (s, 3
H), 2.37-2.56 (m, 2 H), 3 .29-3 .35 (m, 2 H), 4. 1 1 -4. 1 6 (m, 3 H), 4.97-5 .05 (m, 2 H), 5 .70-5 .76 (m,
1 H). 7. 1 1 -7. 1 7 (m, 4 H). l3C: ( 14 peaks) 0 1 7 1 . 1 , 1 39.0, 1 37.2, 1 35 .0, 129.0, 1 26.6, 1 1 6.7, 82.0,
64.8 , 6 1 .8, 42,6, 29.0, 2 1 . 1 , 20.9. Anal. Calcd for C16H2203 : C, 73 .25; H, 8.45. Found: C, 73 .08;
H, 8.45.
49
Allylation of 2-(3-methoxyphenyl)-1,3-dioxane (MJS119lfr2433)
�SiMe3 ( 1 .7 eq)
AC20 ( 1 .7 eq)
2.0 mol % Bi(OTf)s O DC
o O�O�
r OCH3
A homogenous mixture of 2-(3-methoxyphenyl)-1 ,3-dioxane (0.2504 g, 1 .289 mmol),
allyltrimethylsilane (0.3483 mL, 0.2504 g, 2 . 1 92 mmol, 1 .7 eq), and acetic anhydride (0.2072
mL, 0.2237 g, 2 . 1 92 mmol, 1 .7 eq) was stirred at 0 °C under N2 in a flame-dried rbf as
bismuth(III) triflate (0.01 69 g, 0.0258 mmol, 2.0 mol %) was added. The reaction mixture
immediately acquired a dark red color. Reaction progress was followed by gas chromatography
and TLC. After 1 h 30 min, the reaction mixture was loaded onto 60 g of silica gel and eluted
with EtOAc/hexanes ( 1 0190, v/v) for fractions 1 -24 and EtOAc/hexanes (20/80, v/v) for fractions
24-57. Fifty-seven fractions (8 mL) were collected after a 1 00 mL prefraction. Fractions 24 to
3 3 were combined and concentrated to yield 0.25 g (70 %) of a clear, colorless liquid that was
determined to be 99 % pure by GC analysis and IH & J3C NMR spectroscopy. IH NMR: 0 1 .83-
1 .87 (m, 2 H), 1 .98 (s, 3 H), 2.35-2.52 (m, 2 H), 3.30-3 .38 (m, 2 H), 3 .79 (s, 3 H), 4. 1 1 -4. 1 6 (m,
3 H), 4.97-5 .05 (m, 2 H), 5 .70-5 .80 (m, 1 H), 6.78-6.85 (m, 3 H), 7.20-7.26 (m, 1 H). l 3C: ( 16
peaks) 0 1 7 1 . 1 , 1 59.7, 143 . 8, 1 34.8, 129.3, 1 1 9.0, 1 1 6.8, 1 1 2.9, 1 1 1 .9, 82.0, 65.0, 6 1 .7, 55 . 1 ,
42.5 , 28.9, 20.9. Anal. Calcd for C16H2204: C, 69.04; H, 7.97. Found: C, 68.83 ; H, 7.94.
50
Allylation of 2-nonyl-l,3-dioxane (MJS2059fr3463)
�SiMe3 ( 1 .7 eq)
2.0 mol % Bi(OTfh O OC
o O�O�
A homogenous mixture of 2-nonyl- l ,3-dioxane (0.2509 g, 1 . 1 76 mmol), allyltrimethylsilane
(0. 3 1 77 mL, 0.2284 g, 1 .999 mmol, 1 .7 eq), and acetic anhydride (0.204 1 mL, 0 . 1 889 g, 1 .999
mmol, 1 . 7 eq) was stirred at 0 °C under N2 in a flame-dried rbf as bismuth(III) triflate (0. 0 1 54 g,
0.0235 mmol, 2.0 mol %) was added. The reaction mixture immediately acquired a light yellow
color. Reaction progress was followed by gas chromatography and TLC. After 4 h, the reaction
mixture was loaded onto 75 g of silica gel and eluted with EtOAclhexanes (3/97, v/v). Sixty-six
fractions (8 mL) were collected after a 1 00 mL prefraction. Fractions 34 to 63 were combined
and concentrated to yield 0.25 g (75 %) of a clear, colorless liquid that was determined to be 97
% pure by GC analysis and IH & 1 3C NMR spectroscopy. IH NMR: b 0.85 (t, 3 H, J = 6.91 Hz),
1 .24 (s, 1 4 H), 1 .3 9- 1 .43 (m, 2 H), 1 .80- 1 .89 (m, 2 H), 2.02 (s, 3 H), 2.22 (t, 2 H, J = 6. 1 8 Hz),
3 .20-3 .29 (m, 1 H), 3 .40-3 .57 (m, 2 H), 4. 1 4 (t, 2 H, J= 6.42 Hz), 5 .00-5.06 (m, 2 H), 5 . 7 1-5 .86
(m, 1 H). 1 3C: ( 1 8 peaks) b 1 71 . 1 , 1 3 5. 1 , 1 1 6.7, 79.3, 65.2, 6 1 .8, 3 8.3 , 33 .8, 3 1 .9, 29.7, 29.6,
29.6, 29.4, 29.3 , 25 .4, 22.7, 2 1 .0, 14. 1 . HRMS-EI (mlz): M+ ca1cd for C1 sH3403Na, 321 .2406;
found, 321 .24 16.
5 1
Allylation of 2-(2-bromoethyl)-1,3-dioxane (MJS2107fr4460)
o O�O�
Br�) �SiMe3 ( 1 .7 eq)
AC20 ( 1 .7 eq) ,..
Br� 2.0 mol % Bi(OTf)s D oC
A homogenous mixture of 2-(2-bromoethyl)- 1 ,3-dioxane (0.2545 g, 1 .305 mmol),
allyltrimethylsilane (0.3525 mL, 0.2534 g, 2.2 1 8 mmol, 1 .7 eq), and acetic anhydride (0.2097
mL, 0.2264 g, 2.2 1 8 mmol, 1 .7 eq) was stirred at 0 °C under N2 in a flame-dried rbf as
bismuth(III) triflate (0.01 7 1 g, 0.0261 mmol, 2.0 mol %) was added. The reaction mixture
immediately acquired a light brown color. Reaction progress was followed by gas
chromatography. After 2 h 30 min, the reaction mixture was loaded onto 60 g of silica gel and
eluted with EtOAc/hexanes (5/95, v/v). Sixty fractions (8 mL) were collected. Fractions 44 to
60 were combined and concentrated to yield 0.2569 g (70 %) of a clear, colorless liquid that was
determined to be 98 % pure by GC analysis and IH & I 3C NMR spectroscopy. IH NMR: b 1 . 83-
1 .96 (m, 4 H), 2.03 (s, 3 H), 2.24-2.29 (m, 2 H), 3 .45-3 . 5 1 (m, 4 H), 3 .60-3.66 (m, 1 H), 4. 1 1 -
4. 1 6 (m, 2 H), 5 .04-5. 1 0 (m, 2 H), 5 .7 1 -5 .8 1 (m, 1 H). 1 3C: ( 1 1 peaks) b 1 7 1 . 1 , 1 33 .9, 1 1 7 .6,
76.5, 65 .6, 6 1 .6, 3 7.9, 37.3, 30.4, 29.2, 2 1 .0. HRMS-EI (mlz): [M + Ht calcd for Cl IH20Br03,
279.0596; found, 279.0598.
52
C. Bismuth(III) Tritlate Catalyzed Allylation of 5,5-Dimethyl-l ,3-Dioxanes
AHylation of 2-( 4-chlorophenyl)-5,5-dimethyl-l,3-dioxane (EBl 123fr3343)
�SiMe3 ( 1 .7 eq)
AC20 ( 1 .7 eq)
2.0 mol % Bi(OTfh O OC
A homogenous mixture of 2-( 4-chlorophenyl)-5,5-dimethyl- l ,3-dioxane (0.2500 g, 1 . 1 03 mmol),
allyltrimethylsilane (0.2979 mL, 0.2 142 g, 1 .875 mmol, 1 .7 eq), and acetic anhydride (0. 1 786
mL, 0. 1 929 g, 1 . 875 mmol, 1 .7 eq) was stirred at 0 °c under N2 in a flame-dried three-neck rbf
as bismuth(III) triflate (0.0724 g, 0. 1 1 0 mmol, 1 0.0 mol %) was added. The reaction mixture
immediately acquired a bright orange color. Reaction progress was followed by gas
chromatography. After 1 0 min, the reaction mixture was stirred with 1 0% Na2C03 ( 1 5 mL) for
25 minutes. The mixture was extracted with EtOAc (3 x 1 0 m:). The combined organic layers
were washed with sat. NaCl (20 mL), dried (Na2S04), and concentrated to yield 0.3360 g (98 %)
of a yellow liquid that was determined to be 90 % pure by GC and IH NMR. The crude product
was loaded onto 22 g of silica gel and eluted with EtOAc/ heptane (2.5/97.5, v/v). Sixty-five
fractions (4 mL) were collected. Fractions 35 to 5 1 were combined and concentrated to yield
0.2534 g (74 %) of a clear, colorless liquid product that was determined to be 95 % pure by GC
analysis and IH spectroscopy. IH NMR: b 0.87 (s, 3H), 0.89 (s, 3 H), 1 .98 (s, 3 H), 2.24-2.53 (m,
2 H), 2.95-3 .05 (q, 2 H, J= 8.64 Hz), 3 .87 (dd, 2 H, J = 1 0.63, 2.2 1 Hz), 4. 1 1 -4. 16 (m, 1 H),
4.96-5 .02 (m, 2 H), 5.66-5 .81 (m, 1 H), 7. 1 5-7. 1 8 (m, 2 H), 7.26-7.30 (m, 2 H). BC: ( 14 peaks) :
b 1 71 .2, 1 40.9, 1 34.5, 1 33 .0, 1 28 .4, 1 27.9, 1 1 7.0, 8 1 .7, 74.4, 69.7, 42.6, 35 .3 , 2 1 .9, 20.9. HRMS-
EI (mlz) : � calcd for C1 7H23CI03Na, 333 . 1 233 ; found, 333 . 1 247.
53
Allylation of 2-( 4-tolyl)-5,5-dimethyl-l,3-dioxane (MJS2063frl034)
�SiMe3 ( 1 .7 eq)
2.0 mol % Bi(OTf)s o De
A homogenous mixture of 2-( 4-tolyl)-5,5-dimethyl- 1 ,3-dioxane (0.2590 g, 1 .256 mmol),
allyltrimethylsilane (0.3392 mL, 0.2439 g, 2. 1 35 mmol, 1 .7 eq), and acetic anhydride (0.20 1 8
mL, 0.21 79 g, 2 . 1 3 5 mmol, 1 .7 eq) was stirred at 0 °C under N2 in a flame-dried three-neck rbf
as bismuth(III) triflate (0.0 165 g, 0.025 1 mmol, 2.0 mol %) was added. The reaction mixture
immediately acquired a light yellow color. Reaction progress was followed by gas
chromatography. After 30 min, the reaction mixture was loaded onto 60 g of silica gel and
eluted with EtOAc/heptane (5/95, v/v). Sixty fractions (8 mL) were collected after a 50 mL
prefraction. Fractions 1 0 to 34 were combined and concentrated to yield 0.30 g (83 %) of a
clear, colorless liquid product that was determined to be 99 % pure by GC analysis and IH & 1 3C
NMR spectroscopy. IH NMR: D 0.88 (s, 3 H), 0.90 (s, 3 H), 1 .99 (s, 3 H), 2.26-2.56 (m, 2 H),
2 .33 (s, 3 H), 2.94-3 .09 (dd, 2 H, J = 1 7.08, 8.64 Hz), 3 .85-3 .94 (t, 2 H, 1 0.58 Hz), 4. 1 1 -4. l 3 (m,
1 H), 4.96-5 .00 (m, 2 H). 5 .73-5 . 84 (m, 1 H), 7. l 3 (s, 4 H). 1 3C: ( 1 5 peaks) : D 1 7 1 .0, l 39.3,
l 36.9, l 35 . 1 , 1 28.8, 126.4, 1 1 6.4, 82. 1 , 74. 1 , 69.7, 42.8, 35 .3 , 2 1 .9, 2 1 .0, 20.8. Anal. Calcd for
Cl sH2603 : C, 74.45 ; H, 9.02. Found: C, 74. 1 5; H, 9.08.
54
Allylation of 2-nonyl-5,5-dimethyl-l ,3-dioxane (EB1125fr916)
�SiMe3 (1.7 eq) O� AC20 (1.7 eq) �O) -2-.0-m-O-l o-Vo-B-i(O
-T-f)-3-JSo"-
O OC
A homogenous mixture of 2-nonyl-5,5-dimethyl- l ,3-dioxane (0.2500 g, 1 .03 1 mmol),
allyltrimethylsilane (0.2786 mL, 0.2003 g, 1 .754 mmol, 1 .7 eq), and acetic anhydride (0. 1 676
mL, 0 . 1 793 g, 1 .754 mmol, 1 .7 eq) was stirred at 0 °c under N2 in a flame-dried three-neck rbf
as bismuth(III) triflate (0.0 1 35 g, 0.0206 mmol, 2.0 mol %) was added. The reaction mixture
immediately acquired a pale yellow color. Reaction progress was followed by gas
chromatography. After 3 h 30 min, the reaction mixture was stirred with 1 0% Na2C03 ( 1 5 mL)
for 25 minutes. The mixture was extracted with EtOAc (3 x 1 0 mL) . The combined organic
layers were washed with sat. NaCl (25 mL), dried (Na2S04), and concentrated to yield 0.3 1 52 g
(98 %) of a dark brown liquid that was determined to be 83 % pure by GC and 1 H NMR. The
crude product was loaded onto 12.5 g of silica gel and eluted with EtOAc/heptane (4/96, v/v).
Twenty-five fractions (4 mL) were collected after a 1 00 mL prefraction. Fractions 5 to 1 6 were
combined and concentrated to yield 0.23 1 5 g (72 %) of a clear, colorless liquid product that was
determined to be 97 % pure by GC analysis and IH & BC NMR spectroscopy. IH NMR: C 0.85-
0.89 (m, 9 H), 1 .24- 1 .41 (m, 1 6 H), 2.03 (s, 3 H), 2. 1 9 (t, 2 H, J = 6.91 Hz), 3 . 08-3.22 (m, 3 H),
3 .86 (s, 2 H), 4.97-5 .01 (m, 2 H), 5 .72-5 .83 (m, 1 H). l 3C ( 19 peaks) : C 1 7 1 .0, 1 3 5 .30, 1 1 6.48,
79.34, 74.53, 69.91 , 3 8.29, 35 .52, 33 .80, 3 1 .96, 29.8 1 , 29.69, 29.65, 29.39, 25.36, 22.73, 22.05,
20.9 1 , 14. 1 5 . HRMS-EI (mlz) : � calcd for C2oH3803Na, 349.271 9; found, 349.2735 .
55
D. Bismuth(III) Triflate Catalyzed Allylation of 1,3-Dithianes
Allylation of 2-phenyl-l,3-dithiane (MJS2071frl 135)
�SiMe3 ( 1 .7 eq)
AC20 ( 1 .7 eq)
4.0 mol % Bi(OTf)s o oe
o s�s� r
A homogenous mixture of 2-phenyl- l ,3-dithiane (0.2530 g, 1 .289 mmol), allyltrimethylsilane
(0.348 1 mL, 0.2503 g, 2 . 19 1 mmol, 1 .7 eq), and acetic anhydride (0.207 1 mL, 0.2236 g, 2. 1 9 1
mmol, 1 .7 eq) was stirred at 0 °C under N2 in a flame-dried three-neck rbf as bismuth(III) triflate
(0. 0 169 g, 0.0258 mmol, 2.0 mol %) was added. The reaction mixture immediately acquired a
light yellow color. Reaction progress was followed by gas chromatography. After 3 h,
additional bismuth(III) triflate (0.0169 g, 0.0258 mmol, 2.0 mol %) was added to the reaction
mixture because starting material was detected by Gc. After 3 h 45 min, the reaction mixture
was loaded onto 70 g of silica gel and eluted with EtOAc/heptane (3/97, v/v) for the prefraction
and EtOAC/heptane (5/95, v/v) for the fractions. Forty-eight fractions (8 mL) were collected
after a 75 mL prefraction. Fractions 1 1 to 35 were combined and conc�ntrated to yield 0.28 g
(78 %) of a clear, colorless liquid product that was determined to be 98 % pure by GC analysis
and IH spectroscopy. IH NMR: b 1 .67- 1 .73 (m, 2 H), 2.27-2.37 (m, 5 H), 2.56-2.61 (t, 2 H, J =
7.43 Hz), 2.80-2.88 (m, 2 H), 3 .78-3. 84 (t, 1 H, J = 7.43 Hz), 4.95-5.05 (m, 2 H), 5 .64-5 .74 (m, 1
H), 7.24-7.30 (m, 5 H). 1 3C: ( 1 3 peaks) b 1 95 .5 , 141 .9, 1 3 5 .2, 128.4, 127 .8, 1 27. 1 , 1 1 6.9, 49.4,
40.8 , 30.5, 29.7, 29.0, 28.0. HRMS-EI (mlz) : M+ calcd for C1sH200S2, 280.0956; found,
280.0952.
56
Synthesis of 2-( 4-chlorophenyl)-1,3-dithiane (MJS2095fr1444)
o �H
CIN r'I SH SH ( 1 .2 x)
CH3S03H (1 0 .0 mol %)
CH2CI2. O DC
A solution ofp-chlorobenzaldehyde (0.5428 g, 3 .86 1 mmol) and 1 ,3-propanedithiol (0.466 1 mL,
0 .50 15 g, 4.634 mmol, 1 .2 eq) in CH2Ch ( 10 mL) was stirred at O °C in a three-neck rbf as
methane sulfonic acid (0.0250 mL, 0.37 1 g, 0.386 mmol, 1 0.0 mol %) was added. Reaction
progress was followed by gas chromatography. After 1 7 h 30 min, additional 1 ,3 -propanedithiol
(0. 1 942 mL, 0.2089 g, 1 .930 mmol, 0.5 eq) and methane sulfonic acid (0.0 125 mL, 0.01 85 g,
0 . 1 93 mmol, 5 .0 mol %) were added to the reaction mixture because SM was detected by GC.
After 22 h, the reaction mixture was stirred with 2 M NaOH (20 mL) for 1 5 min. The mixture
was extracted with CH2Ch (2 X 20 mL). The combined organic layers were washed with H20 (2
X 40 mL) and sat. NaCl (40 mL), dried (Na2S04), and concentrated to yield 0 .86 1 6 g (97 %) of a
white solid that was determined to be 95 % pure by GC analysis and IH NMR. The crude
product was loaded onto 50 g of silica gel and eluted with EtOAc/heptane (5/95, v/v). Sixty
fractions (8 mL) were collected. Fractions 14 to 44 were combined and concentrated to yield
0.74 g (83 %) of a white solid that was determined to be >99 % pure by GC and IH NMR. IH
NMR: 6 1 .82- 1 .98 (m, 1 H), 2. 1 3 -2.2 1 (m, 1 H), 2.85-3 . 1 0 (m, 4 H), 5 . 1 2 (s, 1 H), 7.25-7.38 (m,
4 H).
57
Allylation of 2-( 4-chlorophenyl)-1,3-dithiane (MJS21 19fr2346)
�SiMe3 (1 .7 eq)
2.0 mol % Bi(OTf)s o oe
A homogenous mixture of 2-(4-chlorophenyl)- 1 ,3-dithiane (02590 g, 1 . 1 22 mmol),
allyltrimethylsilane (0.3032 mL, 0.21 80 g, 1 .908 mmol, 1 .7 eq), and acetic anhydride (0. 1 803
mL, 0. 1 948 g, 1 .908 mmol, 1 .7 eq) was stirred at 0 °C under N2 in a flame-dried three-neck rbf
as bismuth(III) triflate (0.0147 g, 0.0225 mmol, 2.0 mol %) was added. The reaction mixture
immediately acquired a light yellow color. Reaction progress was followed by gas
chromatography. After 2 h 45 min, the reaction mixture was loaded onto 60 g of silica gel and
eluted with EtOAc/heptane (3/97, v/v). Forty-eight fractions (8 mL) were collected after a 1 00
mL prefraction. Fractions 1 3 to 34 were combined and concentrated to yield 0.23 g (65 %) of a
clear, colorless liquid product that was determined to be 98 % pure by GC analysis and IH
spectroscopy. IH NMR: () 1 .68-1 .73 (m, 2 H), 2.26-2.3 1 (m, 5 H), 2.5 1 -2.58 (m 2 H), 2.75-2.91
(m, 2 H), 3 .75-3 . 8 1 (t, 3 H, J= 7.40 Hz), 4.96-5 .03 (m, 2 H), 5 .60-5.70 (m, 1 H), 7.24-7.26 (m, 4
H). l 3C: ( 1 3 peaks) () 1 95.6, 140.5, 1 34.8, 1 32.7, 129.2, 1 28.6, 1 1 7.3 , 48.8, 40.8 , 30.6, 29.7, 29.0,
28.0. HRMS-EI (mlz): M+ calcd for Cl sH19ClOS2, 3 1 4.0566; found, 3 14.0564.
58
Synthesis of 2-(3-tolyl)-1,3-dithiane (MJS2101crude)
(l SH SH ( 1 .7 x)
CH3S03H ( 1 0.0 mol %)
CH2CI2• O DC
A solution of m-tolualdehyde (0.508 1 g, 4.229 mmol) and 1 ,3-propanedithiol (0.723 1 mL,
0 .778 1 g, 7. 1 89 mmol, 1 .7 eq) in CH2Ch ( 10 mL) was stirred at O °C in a three-neck rbf as
methane sulfonic acid (0.0274 mL, 0.0406 g, 0.423 mmol, 1 0.0 mol %) was added. The reaction
mixture immediately acquired a cloudy white color. Reaction progress was followed by gas
chromatography. After 1 8 h, the reaction mixture was stirred with 2 M NaOH (40 mL) for 1 5
min. The mixture was extracted with CH2Ch (3 X 20 mL). The combined organic layers were
washed with H20 (2 X 40 mL) and sat. NaCI (40 mL), dried (Na2S04), and concentrated to yield
0.76 g (85 %) of a yellow liquid that was determined to be 98 % pure by GC analysis and IH
NMR. IH NMR: 0 1 .84-2.00 (m, 1 H), 2. 1 2-2. 1 9 (m, 1 H), 2 .33 (s, 3 H), 2.85-3 . 1 1 (m, 4 H), 5 . 1 2
(s, 1 H), 7 .08-7.28 (m, 4 H).
Allylation of 2-(3-tolyl)-1,3-dithiane (MJS2097fr1334)
CH3
�SiMe3 (1 .7 eq)
AC20 ( 1 .7 eq)
4.0 mol % Bi(OTfb O DC
o S�S�
~ CH3
A homogenous mixture of 2-(3-tolyl)- 1 ,3-dithiane (0.248 1 g, 1 . 1 79 mmol), allyltrimethylsilane
(0.3 1 86 mL, 0.2291 g, 2.005 mmol, 1 .7 eq), and acetic anhydride (0. 1 895 mL, 0.2047 g, 2.005
59
mmol, 1 .7 eq) was stirred at 0 °C under N2 in a flame-dried three-neck rbf as bismuth(III) triflate
(0.03 1 0 g, 0.0472 mmol, 4.0 mol %) was added. Reaction progress was followed by gas
chromatography. After 3 h, the reaction mixture was stirred with 1 0% Na2C03 (20 mL) 1 5
minutes. The mixture was extracted with EtOAc (3 x 20 mL). The combined organic layers
were washed with sat. NaCl (40 mL), dried (Na2S04), and concentrated to yield 0.3263 g (94 %)
of a dark brown liquid that was determined to be 83 % pure by GC and I H NMR. The crude
compound was loaded onto 60 g of silica gel and eluted with EtOAc/heptane (3/97, v/v). Fifty-
three fractions (8 mL) were collected. Fractions 1 3 to 50 were combined and concentrated to
yield 0.2460 g (74 %) of a clear, colorless liquid product that was determined to be 97 % pure by
GC analysis and IH spectroscopy. IH NMR: 6 1 .66- 1 .76 (m, 2 H), 2.28 (S, 3 H), 2 .33 (s, 3 H),
2 .52-2.6 1 (t, 2 H, J = 14.34 Hz), 2.76-2.94 (m, 2 H), 3 .74-3 .79 (t, 1 H, J = 7.37 Hz), 4.96-5 .06
(m, 2 H), 5 .64-5.74 (m, 1 H). 7.0 1 -7.25 (m, 4 H). l 3C: ( 16 peaks) 6 1 95.6, 14 1 .9, 1 3 8. 1 , 1 3 5 .4,
1 28 .4, 1 28 .3 , 1 28.0, 1 24.9, 1 1 6.9, 49.5, 40.9, 30.6, 29.8, 29.0, 28.0, 2 1 .5 . HRMS-EI (mlz) : �
calcd for CI6H220S2Na, 3 1 7. 1 0 1 0; found, 3 1 7. 1 028.
Synthesis of 2-nonyl-l,3-dithiane (MJS2113crude)
o H
(l SH SH ( 1 .8 x)
CH3S03H ( 1 0 .0 mol %)
CH2CI2. O oC
S:) S
A solution of decanal (0.5662 g, 3 .623 mmol) and 1 ,3-propanedithiol (0.6 196 mL, 0.6666 g,
6. 1 69 mmol, 1 .8 eq) in CH2Ch ( 10 mL) was stirred at O °C in a three-neck rbf as methane
sulfonic acid (0.024 mL, 0.035 g, 0.36 mmol, 1 0.0 mol %) was added. Reaction progress was
followed by gas chromatography. After 1 8 h, the reaction mixture was stirred with 2 M NaOH
60
(40 mL) for 20 min. The mixture was extracted with CH2Ch (3 X 20 mL). The combined
organic layers were washed with H20 (2 X 40 mL), 2 M NaOH (3 X 20 mL), sat. NaCl (40 mL),
dried (Na2S04) , and concentrated to yield 0.6959 g (78 %) of a clear, colorless liquid that was
determined to be 97 % pure by GC analysis and IH NMR. IH NMR: 6 0.80-0.85 (t, 3 H, J = 6.9 1
Hz), 1 .22 (s, 1 2 H), 1 .36- 1 .46 (m, 2 H), 1 .65- 1 .87 (m, 3 H) 2.03-2. 1 0 (m, 1 H), 2.6 1 -2 .84 (m, 4
H), 3 .98-4.02 (t, 1 H, J = 6.67 Hz).
AHylation of 2-nonyl-l,3-ditbiane (MJS2U 7fr1519)
s� s
�SiMe3 (1 .7 eq)
AC20 ( 1 .7 eq)
1 0.0 mol % Bi(OTfh O oC
o s�s�
A homogenous mixture of 2-nonyl- l , 3-dithiane (0.2522 g, 1 .023 mmol), allyltrimethylsilane
(0.2764 mL, 0. 1 988 g, 1 .740 mmol, 1 .7 eq), and acetic anhydride (0. 1 644 mL, 0. 1 776 g, 1 .740
mmol, 1 .7 eq) was stirred at 0 °c under N2 in a flame-dried rbf as bismuth(III) triflate (0.0671 g,
0 . 1 02 mmol, 1 0.0 mol %) was added. The reaction mixture immediately acquired a light yellow
color. Reaction progress was followed by gas chromatograph. After 3 h 30 min, the reaction
mixture was loaded onto 60 g of silica gel and eluted with EtOAc/heptane (3/97, v/v). Eighty-
eight fractions (8 mL) were collected after a 50 mL prefraction. Fractions 1 5 to 1 9 were
combined and concentrated to yield 0.2 127 g (63 %) of a clear, colorless liquid that was
determined to be 97 % pure by GC analysis and IH & BC NMR spectroscopy. IH NMR: 6 0.83-
0.88 (t, 3 H, J = 6.67 Hz), 1 .24 (s, 14 H), 1 .3 9- 1 .58 (m, 3 H), 1 .79- 1 .85 (m, 2 H), 2.27-2.32 (m,
4 H), 2 . 5 1 -2.64 (m, 3 H), 2.92-2.98 (t, 2 H, J = 7. 1 5 Hz), 5 .02-5.08 (m, 2 H), 5 .77-5 .87 (m, 1 H).
6 1
1 3C: ( 1 5 peaks) 0 1 95 .6, 1 35.7, 1 1 6. 8, 45.3, 39.3 , 34.2, 3 1 .9, 30.6, 29.6, 29.3, 29.2, 28. 1 , 26.7,
22.7, 1 4. 1 . HRMS-EI (mlz): � calcd for C1 8H340S2Na, 353 . 1949; found, 3 53 . 1 963.
62
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69
IV. Appendix: Spectral Data
70
rJ1 "d � � ..... .., = = ....
:::r:::
� o >-+, � [/1 tv o VI -....) ::p tv o VI .......
�l
x 'E a ;; .. "" � o· := '"' ::tl
7.5073 7.4780 7.3947 7.3022 7.1053 7.0989
5.8636 5.8379 5.7995
5.0742 5.0375 S.01}37 4.7079 4.6978 4.6795
.... g
)0 ' o
�
�'C . __ r. "
. ...--'"
/;c� ;",
� ''-...... <:) -� .... ,/"
" ', " U. / ' /' Q
", ;'';''
/ 4.1804 '-... 4. 1 566 4. 1 328 /" ... ;",
�:�:g� ;>�i 3.3388
2.4377 2.4194 2.3928
1 .9899 1.8883 1.8654 1.8425
0.0549
�
" .... :';'-' "
...... N � ........ �. ,b " //.
..... ;", -
0 -'
,_ • .. -
(Millions)
o 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 1 1.0 12.0 13.0 1 4.0 15.0 16.0 17.0 18.0 19.0 20.0 2 1.0 22.0 23.0 24.0 25.0 26.0 27.0 .J..tJ .. t...t.. J...d • .l.L.I...Ll..t..u..1.LJ.L.Ll. LLLt.LLLl .u.Lt.u..L.l.l.l,.l.. d . .1.Lu.l..l.1.I...LJ...Lu.JH1J .. �1.d_L...Lw .. l..r_w. • .d.J�� .. l,J�Lu ... u...LI..L.I •. .d ... UJ....lJ...J...w.L...u....t..1.w.L.l.,1.J ... ILL.1.J,..t.l.J..w...L.lu..LLlLLW.J..)..L,.I . .r.�
j 1 co .....
o )=0 (�- -----
_ .. _ .. _ .... "'----�
-\
�� [ ---�-----·I r·=iffiiE· ····,,======----- ---------�
I
[��----.---------. �
L-T
�---------.
� til ..... ::r tv 8: ;1: ..:.. !?;;
�
t"'57f"'51��2'" o � 0-] 8 �
i ,i-,'-"'TI "', ;"""", ,.., '"', ,'""""'TI " . . ,-y,"", ,-' ,.." ,,",,T' rl n, ,-,.,,..,,.., ,M'''''''' "I '''''T''''' n. '''T''''' ,.., (,",'''''''' n. ,,,,,..,.,,-, '" ,'"""'" .... , ,M',",,"" "" ,,,,..,.,.,-, """,..,..,..,-., ''',,",,, ,.., ,",, ,,",'T''''' n. ''T,T''''' ,.." ,,",,,T'''-, ,n,'T,"" 'i"" ,,.., .... ,,.., M, ,-r'ITT'1 .n,-"''''' .,.., ,""'-"'TI MI ,n,..,., ,.., n. ',"".,.., r, n. ''"1''T' .,.., ,n,..,.,"",,",,,,,,,,,,, ,,,,,,,,,,,,,,,,,,,, n[ ,,.,,.,.. ,.., n. 1M,""' ''''' n[ i"""', 'r' .r.,,,,,,,,,,. ""1 11"'1'''''''''' ,"" ''''',"",,.., ", ,,'T' .... , ,M,.",,.., n. ,nl"'''''' M. ,-r'T' '''', .n'''''I''''' ,,", ,"',"" • .,.., ,,,,.,.'TI ,-,. .. 200.0 190.0 180.0 170.0 160.0 150.0 140.0 130.0 120.0 no.o 100.0 90.0 80.0 70.0 60.0 50.0 40.0 30.0 2,0.0 10.0 0 . '., i \'\
,� - M <:> - .... <:> M - "' <:> .... .... Q "" .", l"- _ � ::::; ':1 .,.. "" QO l"-"'; N o:S � M � ::::; !:! � � :! �
.... '" '" III N <:> ::: � til ,.., Co 1.0 � "" r-: :l "" :g "" .... "" "" N N
X : parts per Million : DC
Spectru� 2 l 3e NMR ofMJS2057fr205 1
<J) 't:I � � ""! 1:1 = w ::r: � :;;0 o >-i") � r:/1 ....... ....... 00 Vl
� Vl o 0'\ \0
�
"<:I ,. iii> 16 ... � 0 = ,... �
(Millions)
: 0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 n.O 12.0 13.0 14.0 15.0 16.0 17.0 18.0 1 9.0 20.0 21.0 -Lu...l...l-Lw ! t I . j ! J I ! . I I I . ! I ! ! t I ! ! I . ! ! I j , I I I 1 1 I f , I , I I r I , ! I t I f I r , I . , J I f I ! t ! ! . ' I ' I ! , I I I , I I ! I , I , t 1 1 I ! t I • • ! . ! , . 1 I !
,; p
7.4524 7.4213 7.2464 7.1438 7.1136
, "
'""' g
�
�
............
.... _-.....
---... � <:>
� �'�i:� �� 1 � 5:6886 ?-- = 5.6529
::::, '" .� L. l 5.0055 / .<:\ ( 4.9625
4.1493 �'" 4.1255 7"'ot. 4.1016 b
3.3269 �,.:.; 3.3132 7"" 3.3040
2.5265 2.5000 2.4743 2.3434 2.3177 1.9771 1.8590 1.8361 1.8132
w <:>
�;� ?�': .......... !" >fjQ
1.2317 --. . ... .
,.. <:>
c:>
......
�
OJ .....
� o /=0
"I
-,
! .... � ::;0 ,.
! e;
mjs1185frac5069car-2.jdf
I I �O.O ,' 70.0 60.0 50.0 40.0 30.0 2p.0 10.0 0
/\\ 200.0 140.0 1l0.n 100.0 130.0 120.0 190.0 180.0 170.0 160.0 150.0
r--- tf"I � '>C N '" o.n o.n '" o ....... - t--- ... '" � � � - Q � \C o.n � '=' 'O ''''''' \Q � "" 5 .,..; � t--= w vi ... M '" C/C t"-- t-- I:'"-- \CO \CO � N N
X : parts per Million : 13C
Spectrum 4 I 3C NMR ofMJS 1 1 85fr5069
mjs1185fr5069dept135-5.jdf
� I
200.0 190.0 180.0 170.0 160.0 150.0
X : parts per Million : 13C
I 140.0
N "" .". M ..,; :;
130.0
'" '" tTl "" .". 1Il :2 ,.. 00 :; �
I ' 120.0 1 10.0 100.0
.... '" .... .., � �.
I 90.0 80.0
.... <::> � ;;
Spectrum 5 DEPT- l 35 ofMJS l 1 85fr5069
70.0 60.0 50.0 .40.0
"" '" tTl "" '" "" :! "" '" � -..; � '" "" ."
30.9
." ." tTl '=! "" N
20.0
\to '" '" ;; N
I 10.0 o
1 ; �I � �j � 4 t
! : [
, '
, ,
: �.l; i
�'�l '�"�"�'�l '�"�' �"�' I�' I�'�jj�jj�t 1�'�i j�j(�j j�' �" �"�I '�"�'�"�il�' j�'�li�"�l t�' �I I�j l�I I�'�iI�"T! I�' �ll�"�"�' �I I�Ii�\ I�' �ii�I I�II�' �"�"�"�I �li�Ii�"�' �l lnj l�"�' �i l�"�" �" �'�"�"�"�J �"�"�i1�'�l 'nj l�1l�'�j '�l j�' j�' �" �i J�' �ii�' l�"�' iI �i �������� 170.0 160.0 150.0 140.0 130.0 120.0 1 10.0 100.0 90.0 80.0 70.0 60.0 50.0 40.0 30.0 20.0 100.0
X : parts per Million : l3e (Thousands)
Spectrum 6 HETCOR ofMJS l 1 85fr5069
00 "'0 ee � .... ""i = :3 -...l ::r: z � o >-i') � 00 ......... ......... -.) \.0 ::p 00 o \.0 \.0
x
't) ., it � � § iii
" "-.
-p -<::>
�
� �;
7.2976 7.2665 7.1978 7.1 658 ;> --I Q
5.7546 "-,,-5.7189 .
5.6886 , .. -;; .
5.6529 ./
'" Q -
5.0174 � .. !" 5.0018 / .:Q 4.9588
4.1483 -, 4.1245 -' .I>, .
4.1007 ,/ Q -
3.3342 "" 3.l2S 1 /" .
3.3123 r' w b -'
2.5027 " " �
2.4762 2.3461 ,..-"'..-2.3196
1.9725 �'" l" 1.8590 " '" c 1.8351
/;�. 1.8[23
,... Q
0 ·"
(Millions)
o 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 1 1.0 12.0 1 3.0 1 4.0 l5.0 1 6.0 17.0 18.0 19.0 20.0 21.0 22.0 23.0 24.0 .1,J..LI.l-LI.J.J.J..f.Ld-.l.,L ... ,�.l,u .. 1,J . .I..I..I,.L.l-L1..u...Lll...LL...J_L.J...l.l_Ll.J.....L_l.L....l_1..J.,.L'-t..w.J . .L.J. • .l.J_l.1.J.J_I.l.,1,.L,�.J�J,.t..t.Lt.l .••• .u. . .LLl.l...L.-l.l..w....t...t..L,J..,.,l....l..l.J..t�wJ..J...w. . .t.L1...L.J._.t...l....t...U • .LLL..w....t.
Q
1 o )=0
�;.�' "W'h
--��-.,--� .... -.-�--•• ---.--•• -------------------l
�I COC=· . ----·-··---·-----""'-�··-........ �_. __ .��N_�. ,--� ... ,� ......... ,
.. .. _-_ .. __ ... __ ... __ . __ ._ ..... _. __ . __ .,
�--..... --� .... __ ._--"'"'\....
L= -.. ----.----.. -�
----------_.,
2. '" ..... ..... � ;i' &, J 'a: ..,
�-;�,�: .. -" , --------=--_ .. _._
. __ . __ ... _--'-----)
L .. �.���,�. __ '._.M._.'_ ._._._.,._ ... _____ " .. __ .... �_,_ .. _" .--. .....• _��,_. __ .• _ •. , ___ .,� ..
I'-II ! . I
j i " i l " " I " " " " I ! I I I " " " I " " " " ' ( " " " I I ' 1 , , 1 , • . , 1 ' 1 , • . 1 . 1 " ' 1 , . , . , , 1 " " " " " " 1 ' " " " i 'X" " " " ' l " " . " " I ' · ' · ' · " ' I " " ' " · ' I ' . " . · · I · l " ' · , i l i l j • • • • • • • . . j . l • • . i . , . j ' . , i . . , . 1 1 1 " • • . , 1 ' 1 200.0 190.0 180.0 170.0 160.0 150.0 140.0 130.0 1 20.0 . 1 10.0 100.0 90.0 80.0 . 70.0 60.0 50.0 .40.0 30.0 20.0 10.0 0
/ \ ,... M ... ... ... - ." N '¢ � O\ ... ""
l§ <::> <>- '<> ¢O N .". t- N QO N M '" <>- ... .., 00 "" <::> V1 N "'=f OQ ;:: Q\ "" C'l "" <n O 8
f,(') ,¢ - '¢ "< E d � M 00 00 ...: � � � vi G :::: � � !:"! � 00 t- l.""'-- l' ""
-
X : parts per Million : l3e
Spectrum 8 I3e NMR ofMJS1 1 79fr8099
m,I!!20S1fr3052-4.jM
I' .
.
,--
,--
i-J
0
O�O� ~ r r
i
f j� . ..1 t j'J�v 1 ...I.! • J . ...... 10.0 9.0 3.0 7.0 6.0 /1\ 5,q 11\·0 3.0 :t? ,\ 1.0 , 0 / ;\
� ' lit 1\' '1 \ j 1/ \\ j;\ /11 I , , l \ I ;
�¢'\"'$ "' .... $ " .., .., ii�g ")It> '" !'"'''S; .... .... .." " i � t! � ��" !�! "' ... ... i�"'= ", ,,, ... g;::! ... �;:!;:;:: .... .. ,.. "l"l"l "l "l "l "l . .� . • �..¢'lf!�"". � . il' ... .... _ . � ":"'lft.tdi.n ...t V � "' ''' ''' N N N <"l ...c ..,c ..... 'I'!"'l <l>
X : jIIlI1!I per MiI&Ja : 18
Spectrum 9 IH NMR ofMJS205 1 fr3052
mjs20S1fr3052car-2.jdf
o O�O� ~
°NM��� � �'�' rl .n" '�'�'�' MI Ln" ,"T' �1 1�'n" " " 'rl n"r..""T,�. 'n'n1"T'rl .n" " 'T'�' rl ,n" 'T'�' r. ,n" " lr, n' in" 'T'T'r" �I" •. r'T. r, .n" " 'Tl r •• n" " 'T'�' rl i�I".'�' r' in'n" 'T'TI M. 'n" ,.,r,r •• n'nX".,r, r" M" " 'T" j ,n,n .• " ,r, n, .M'nl.,r,r, n' In, •. T'�' ni .n, ••• ,r. n, .n" '., T'r' nlt".'T. r' M. ln· ••• " 'r,IM'n.,.""r,.M" ,.,.",r'jn" ,r,r'T'n.'n" " IT'rj.n.n" 'T'T'�'!n'n'T.�'�'n'·""T,r'n'.
200.0 190.0 180.0 170.0 l60.0 150.0 140.0 . 130.0 120.0 110.0 tOo.o 90.0 80.0 . ' 70.0 60.0 50.0 . 40.0 30.0 2,0.0 10.0 0
/F 1 \ i\ / \ � "I!!f" 1:'"-- 1:' co t- � _ 'd" O "'l:t '" "., "C W - ",," <::> r- "., Q lI'l _ ,¢ ¢) � "., N r-: r-.:"&i ..". '" <;o r;--. :r;--.. t:" "" "" ..".
);; ,",," .,., � � � :1 � '" '" "' .... X : parts per Million : 13C
Spectrum 10 l 3e NMR ofMJS205 l fr3052
CIl "0 � t":) .... ... = = .... .... ::r:: z � o >-l') � CIl ....... ....... \0 ....... ::p N +:>. W W
�
'g it � is: § g s
7.2583 7.2280 7.1996
6.8489 6.8187 6.7821
.... <::> ¢
� <::>
r;;
�.,," / -..) ¢ , --
/'"
""
5.8040 ¢
5.7665 � -5.7408 -j : 5.7024 /'
5.0495 ,_ Ul 5.0092 - .-.'�; ¢ 4.9744 /'
4.1621 � ;, 4.1383 / .. .... . 4.1145 ¢ '
3.7903
�:���� �§! 3.3251 /'"" 3.3031
w ¢
2.5220 �,�, 2.4954 ------;;'" 2.3754 /''"'
, 2.3535
1.9808 � .. !;; 1.8718 �'" 1.8480 7--:" 1.8251
... ¢
<::>
(Millions)
o 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 1 0.0 11.0 12.0 13.0 14.0 15.0 1 6.0 17.G 18.0 I' ' II ! , t ! 1 . , . I w...l-J ' 1 , t I J t , ! , ! ! r ! ! ' .L.I.R���l....L-1-l....l-..t..J ! t ! , ! . ! t I ! t ! 1 I I ! j . " . 1 " , J ! I ! ' / LJ.....LJ.....l.l..J.-t..I-l....W...1.. .
�
o o I V>
L· �_. ___ � ---"::::zss=
c� I
�
1 o (=0
I
")
.E. ::: :::; fS ... J, 1 0. ..,
--I
i c: '" :; s E-
� '" j j J o j ..;-] .... ' j i
3 "' � <:> ..., _ 1 �
� o::>
o O�O�
~ OCH3
' t . , ' j • , i I • 1 . , • I I •• i , • • • , I ' • • i I I , j l, • • i • I. j , ' i ' . . I l i t . j I ' L j , 1 i i . , [ I • I, t" , . I • t I , I. , . • I •• , , i •• , i l' . , I i . , • -:l' I , i , I i ,j { j • • , I . II • t j i i ' i • • • • , •• I, , ,j • , \' . , i i , i i , ! [, . . • , ' I . i . . • I I " t . j I I • I • t i t . 1 I . I • • • I I I I' I , j j . , I. t 200.0 190.0 180.0 170.0 160.0 150.0 140.0 130.0 120,0 HO.O 100.0 90.0 ,80.0 " , 70.0 60.0 50.0 40.0 30.0 20.0 10.0 0
� .... "" Q ....
5 � .,.. . '"
"" ..; :::: � .� X : parts per Million : Be
"" to "" .... "" 00 <:0 .... <:> "" .,.., "" '" <'l - '"
-.i � � � :::l ;::: - ...
/ \ 00 <'> 0 '" _ N � ¢! � �
! J/\ .
Spectrum 12 1 3e NMR of MJS 1 1 9 l fr2433
rJ). "0 ee � ..... � e ..... f.H ::c: z � � o >-i; � \./J N o Vl \0 � w � 0\ w
� .. 1 � s: I§ § ill
7.2454
5.8022 5.7756 5.7381
... �
g
00 <:0
.... (:,
0\ (:, "'-... .. ;;;:.::
(Millions)
o 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 1 1.0 12.0 13.0 14.0 _, ! I ! ! " ! I ! . J 1 ,I ... u ... L.WJ ... LLLW..1.J . ..I."UJili.l..U .. LJ..l t ,1 , . " ! ' ! t , ! f f ' I ! " t j 1 , LJ...l..l..LLu..l.u...u..u..w..w.J.J.J...U I " ' ) ' t " , ! " I I , ! , ! I l f .wl..w...t�.! , I , r t ! , I ! ! ! . , ,� . �
�
i .:... e;
� o )=0
5.0678 ''-.'"
�:�m ;;: ·(:,1 r-·---1
4.1648 '---" 4.1410 ;'/."f>
4.1172 0:>
3.5137 ':::-::i: -�--l 3.4908 > i F 3.4597 /."., 3.4368 / _. 3.2482 �
'----
;:::;,� 2.2445 2.2188 2.0256 1.8745 1.8507 1.8278
1.4386
1.2408
/" �-... (:, 0.8818 "'-,.. .
0.8580 7 ' 0.8324
0.0485 0::>
C -�l
=�
r.f1 "e � � "* .., = 9 .... ...
w (J
� o H") � r./J N o Vl \0 ;:p W ... 0\ W
x ] a � a: f -'"
t-.> c ? c
.... \0 ? c
.... co ? -c
("J 171.1737 .:::; c
135.1666
1 16.7850
<::>
.... <!1> ? <:>
... ;!l -C
� � c ·
,... t-.> ? C
g
C; . gl-: "" ? <:> •
79.3492 � � 77.5691 "'-. .:c 77.0955 7 ' . 76.6294
65.2536
61.9149
�
' <!1> • g
� Q
� 38.4068
._v"' . ... �=
33.9222 -... . 31.9816 ,-.. :--- '
. 29.8348 ---' � Z9.6743
. 29.7049 �:'b 29.4375
...
29.4070 � .N 25.4647 r"? 22.7602
<:>
21.0565 14.1958
-,-.... ? -c
Q
(Thousands)
() . . 10.0 20.0 30.0 40.0 50.0 60.0 70.0 80.0 90.0 100.0 HO.O l-L.LJ...LJ_, • .l.J.J . .LL,...L..i.-L..l.ll.l j I , ! ! t , 1 ! • I , , , ! t ' I r " , " ' " f • • , , , I ' , ! I . ) ! f ! , . ! 1 I . I I t t ! ! ! , I • • • ! , ! 1 I ! I , t t ! I ! , ! • I , ! , ! • , , ! ! I ! ! I I I
1 ° (=0
.§. � cr; "" 5; t fiJ � l c � ...,
00 "0 � � """ ;:! 9 ..... u-. ::c:
� o ...." � r:/1 N ...... o -..J � ..j:::. ..j:::. 0\ o
x ." '" � � � = �. =
7.2454
5.7573 5.7354 5.6960
5.0852 5.0641 5.0238
ii> . Q
:.c <::>
co 0 '"
;-l <:>
g; '> . //
'-. . , > 'tit /' C
4.1483 "-. .. . 4.1255 ... . .. .. """ 4.1016 /" 0
3.4972 3.4817 3.4734 3.4606 3.4377
2.2555 2.0210 1.9377 1 .9267 1 .8745 1.8516 1.8278
�.: / ..., o ·
� . � � ;; .... o ·
¢
(Millions)
o 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 1 1.0 12.0 13.0 14.0 15.0 16.0 17.0 18.0 ,-..tJ....,�.L...L.I-j • ..I�.J..J ... .J_LJ._L..I._l�lh.LLL_LLL....l.._Ll,J..J.....l..J._J.JJ.JM.J�.J • ..l.J_J •.. Lt.....L.LI�LL..LL..1.......l.-.Il_.l.....t�l-1-l..i ... LL.J._l......L..LJ.. •• t_l.,.L..J I ! 1 I • • • I r ,_.I,_Ll-J_W_,LL..L.J-.l-L.J.....J....l..
� �� L __ _ � .�:=-
"
--�
OJ ....
IJ 1 ° >=0
... ---.-.-.-.. ------.---------�
��.-.. ----...... -� { -- ----$if-
E. � "" ...., ::;-....
1 9;
.. -�
" -!mjs2107fr44-6o-2.jdf gl
." .; .:$-1 - 1 � -1
o O�O�
Br�
,
C> __ � __ �
I i �·.�' rl �. 'n,�.�,�. �' r' inl�'�iT'�' �I .ni�j�'Tir, �, .n'�'T'T'r' �) {r..�'�'�' r, rj ,r.'�'�lr'r' ri jn" " 'T.r' rl jn,�" ,r'�' ri jn'n.,'r,�. r' .n.",'r'rl rl 'n" 'T'r'r' r.' lnl"T'T.�' r, tn.n" 'T'Tirt in'n','r,�,rjI�'n" 'T.T'r . • n,n" I,.r.r,r'in.""T'rlr,.n'r.."�'T.r'r"�" " 'T'r.r"n'n'""r.rl.n,n" ,r.r.r:.r..""r.r.r.,'n" I�'T.T,r.r.,.n'T" 'Tjr'rjln.n" 'T,r,r'jr..n" 'T,r,r,r'IM" ,T'T'T'r,.n'T,T.T,�.rr"
200.0 190.0 180.0 170.0 160.0 150.0 140.0 130.0 120.0 110.0 100.0 90.0 80.0 70.0 60.0 50.0 40.0. 3"." 20.0 10.0 0 / \ I \ ! \ I
i \ '" t- � � � t- o. '" on 00 '" "" on <; "" "" ..... ... - 00 <Xl ..... "" ..... '" "" .., _ on "" '" .... <:> ..... "l ""': � "l "l � � � f'P) "'! ..; � . , ..... r- "" � � oo t- c:> e. -
::l t- t- ..... ,., ,,, <'> '" '"
X : parts per Million : 13e
Spectrum 16 l 3e NMR ofMJS2 107fr4460
00-� � � .... � 9 I==' -l ::r: � :;;0 o I-+) m ...... ...... tv W
� -l � W
><
1 � i 1:1 "
.-1;
:.: �: �, ! = ;1 - �
�
7.3004 7.2692 .... 7.1850 ;.,/ "l 7.1539 0
0\ <:> 5.7903 �._. 5 7546 '-'''-',.:: 5:7244 ;/'" 5.6886
5.0192 ::::::" .� 5,0055 /.- . 4.9615
4.1410 4.1337 4.1126 3.8864 3.8782
:::::"" " / � ?c ... :
3.0265 ....... -.:.:� 2.9780 ;;::: ''''' 2.9460
2.4780 2.4496 2.4249 2.3452 2.3187 2.2976 1.9890
1 .5879
. 0.8992 0.8763
0.0549
............ ..
��:� j ' N / ' 0
....
'_.-;,,,}::>
""
(Millions)
o 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 1 1 .0 12.0 , " ,I ' ! " " I..J..J...l..J..J..L..LJ..t.J..I ... t..l . ! f l • • • " I • • , . , . " . I , · " " , ' t ' " " f l " ' ! " ! I ' ! " ' ! " ' ! ! I , ! , ! . , ! , . , . • . ! , . , ! . • ! " I . ! t ! t l t ! j l • • , . , . " ' I I I " �'
C;! '"' .... el l:I' Il1
o S - L t ... e;
o ff� o /=0
�._ ·s ________ ......
�.::. ----7
---l
-I
-�
..... -= � " <:> �
EB1123fl"l'lc37-43car-2.jdf
"" .;; ""
Q .;; .....
"" .;; -.0
"" .;; on
"" �
Q .;; ,..,
i J J
�i "" g
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: i I I t ' • I , • • I I ,1 [ • • , • I , j , t , I i i i , , I ' j • , , , , , • i ' l , • i , j • • I ' • I • • • I • I I t , • , .1 . l • t t • l I , i i , • 1 t •• l • • I , , I I , I i i , i ) IJO' • i J , • • I i I • l • • • , • . j I • . I t . , i I \ J I , ( • 1 . • , I I . • , I • , , i • i i • • • j •• i i i ' . i • • , • , , j • • • I I . I I I I ( I i . , • I • [ I J • , • • • • • , I . 200.0 190.0 180.0 170.0 160.0 150.0 140.0 130.0 120.0 1 10.0 100.0 90.0 80.0 .... . 70.0 60.0 50.0 . 40.0 30.0 20.0 10.0 0
"" '" "" 5 :!
X : parts per Million : 13C
e-. "" "" "" 0 "'" "' -� M "" "" ... -
i, f \ , ,
", e-. ... "" - "" >0 O Q6 06 "'" '" - ...
Spectrum 18 J 3e NMR ofEB l 123fr3743
, \� " i ! \" '\
(Millions)
o 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 1 1 .0 12.0 13.0 14.0 15.0 16.0 17.0 18.0 19.0 20.0 2 1.0 22.0 23.0 24.0
J f ',I . , ! . I . Ll..t..l...w...1.J..LLI_.l_d_.1....1_I...w..J...LJ.J..lu..w..L.t..J... I.J...l.J •• LJ.J..LJ.., ... l • .t-i.LJ....l..-,I....l....1...L�u..L..Lu....wJ.Lw • I • • 1 ] r , , • , ! ! I ! , ! t , I I I ! • , ! I , ! , t ! , r ! I ! • , r , I , ! , , I , , ! ! at I
:><! 'g a � :.z: E g iii
.... � -
�
00 o
,g' 7.2445 eo 7.1365 � a � = e
,... \0 ::c
� z '.M" � . [ � ':7 5.8077 -< �
I ,:::.,
5.7821 "/ � 5.7436 o H-,
� ---I <-< 5.0430 = -'-
I C/l
5.0064
I N 4.9716 o
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8 f\.1456 � , 1 C--l. . . �
" 4.1355 // !>-..-�:;��i /' Q [_ ••. =_.
3.901 1 .
3.104: '::,"w c:' -- ==-'-- ____ '\ 2.9789 / .. ")71 •.. • � . C 2.""
. __ � 2.5339 �.'. '." C;; '-=-2.5064 '.r-7 .... 2.4789 /J:;.: (_
. __ , 2.4533 / /
\ 2.3645 N 2.3370 ..... 0 - r 1.9945 -
0.9111 0.8901
.' 0.0769
:-' '--. Q ----.-
""
I-
:j
'1;; ' � l:l � j c., ...
�
16M 1S0.0 14().0 13(),O 120.0 I 1 1{l.() 90.0 So.o . . . . 70.0 60.0 50.0 40.0 30.0 211·0 10.0 0 1 /'0\ \ /!\ , ; :
2(1);0 180.0 170.0 190;0
..,. ... .... 00 0 "" 00 'C 'C O\ c:> o.. 00 .... .... "" -- - eo- - ,", .., 00 �n� � � � 0 on 00 0\ 0 "" '<> - <'> = �:, N "" '<> - <'> "" on "" '" "" '" .t'<,;.' .... ,.,:::;; � � ;::!� � � <>') "": "": � � c;:: t-= � ¢: -6 , . ...o!.,. .... '!J '" .... ... = <'> <'> '" .... .... "" ,-('., � ... � ..... � �'.� 00 t'w l""-- t"-- I:""- 'o.O '" "' ''' ... - .-< - - - '"'
X : parts per Million : Be
Spectrum 20 l 3e NMR ofMJS2063fr1034
iJ1 "0 � � ..... '"'l = = N i-' ::c Z � � 0 >-+-, tr:I b:i ----tv Vl i:t' \0 --0'\
:><: . . ." .. a � is: f s
... g;
�
�� 7.2464 .. . . ...
� � �
0\ � .. 5.7930 5.7674 /'" 5.7299
5.0467 '-...... . '" . 5.0156 /' � 4.9780
"'" � 3.8654
3.2253 �" 3.1932 3.1218 7 -··� . 3.0897
2.2234 �." 2.1978 /" N 2.1758 /'" .. �
2.0339
1.5943 1.4176 1.2829 1.2408 ..... --�---
0.8956 '-...... .. � 0.8608 -... . ,,'" 0.8351 /'
<:>
(Millions)
o to 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 11 .0 12.0 13.0 14.0 15.0 16.0 17.0 18.0 1 9.0 20.0 21 .0 22.0 23.0 1 • ..t..LJ...t..J • .w . .w�w..l.WJ. .. d . ..t..L.I...L.! . .1...1....L...LL,l . .J • .Lw..w.J"i . ..l..,-d-'-1.J,...t..1.1 .. Lw...LJ_J_J.J...LJ_.LL.l I ! 1 , ! ! , I t W .. w .. w .. .LL.LuJ..J....l...J.,J...L w...l 1 I I ! ! , ! t , ! ! f , , • , I , w...t..l..u..w...Lu_.u.l..
trl I;!;I
I
I
0 ( � 0 (=0
.... .... ..., '" ;r 'f' .... "" -g (ll 1.. � .."
---�-��=====-------------------------------� ----;
00 '"d � � -'"'l = 9 N N
w n Z � o >-i; tr:1 OJ ....... ....... N Vl � \.0 ....... 0\
><:
'g al � 8 ,...
tv
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g
)l) 171.0896 ,... ...:t .
, <::> "<:>
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g ,... � <::>
135.3042
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1f6.4870
,...
g
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00 • 79.3416 - P c:> 77.5997 77.1260 ;; : ' .
, 76.6523 / ...:t 74.5361 69.9139
p C> "
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38.2922 �
35.5265 ......... <::>
33.8076 ' " 31.9663 --" 29.81 19 . .;' � 29.6973 ?';"<:> 29.6591
.
29.3917 % 25.3654 ::; '" 22.7373 ?l P 22.0573
<::> •
20.91 1 3 14.1576
... --....
::; "<:>
<::> -
(Thollsands)
o 10.0 20.0 30.0 40.0 50.0 60.0 70.0 80.0 90.0 100.0 1 1 0.0 120.0 130.0 .�., . , ! • • 1 . " • • , ' •• L.J .. Lt..LLWJ..LLI..lu...w..w-U."L..!...J..M .. w..u.L..U I I ! ! 1 1 1 , 1 1.J..I..1.t....w..l.I-U . .L1 , ! , I I " I I I ! ' 1 . 1 I I " ! ' I I I J I t. •• u ... u_u ... d..l.J..L.I..I..1..I...L.I." " I ! . I . ! t ' ! ! ' " I ! ! I
� 51 ;t ! g-
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rJ) "0 fj) !':) '""" "1 =: = N W tI:
� o >-+, � C/) N o -.....l ....... � ....... ....... W Vl
>< 'E � 1 ., � § =
.... g
�
00 e:,
7.2985 � . 7.2839 ;;:: .. 7.2436 �
� 5.7015 � . .
(Millions)
o 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 1 1 .0 12.0 13.0 14.0 15.0 16.0 17.0 IS.0 • , I I I ! 1.-'-.l.�.J�L..1..J...J......L.l....t...J....L.L..i • ..1�l..J......i-J ••• LL.L.J._L.,r�,.l-J�.! •• LJ....L.l�l.,.L.I ... l .. .i-•. L .. Lw ... I-L..LLJ I , I , , t I I • t 1-�.L......l...I-.l.J,�I_.t....J."""�L • .J....J-.
II 1 (f) )=0
a. :-;.. s .... 5: .... � J. �
(
5.6758 7::· : I I -I 5.6383
5.0467 ------• . /Jl 4.9890 "-'''' :.:;:' 4.9524 ./
" i � .-�
3.8352 � . 3.8068 ;;-3.7793
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?' �" o 2.8516
2.8214 2.6145 2.5879 . 2.5604 ./ 2.3177 2.2939 2.2720
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mjs2071fd 135car-2.jdf
o S�S� r
" ' I " " " " ' I " " " " ' I " " " " ' j " " " " ' I ' . 1 . , I I I , I [ . I . , , · • • I . · •• · [ · . · l • • • • • • • , .] , . , I I • • • • j " . 1 . 1 I , 'I' • • • • • " . I I I , ' I , ' . ' I " • • • · . , · I · I , . I • . · · I " ' . · ; , •• ! • • • • • • • • • I ' . ' . " • • 'I •• I . l l i l , ! " I I " · " I ' · · ' · " · ' I '
200.0 190.0 180.0 170.0 160.0 150.0 140.0 130.0. 120.0 , 110.0 100.0 90.0 80.0 ,: , 70.0 /1\ /:\ ... � 00 00 "' "" 1;cl "' ''' ''' '" '" � � tt "' ''' ''' on '" '" '" ", r-. -"'l '" M <0 <:1\ .. '" � � � \f) � vi 06 r-:: r--: � r-- r-- \Q
:�.� � "' M '" r-- r-- r--- - '"' -X : parts per Million ; Be
Spectrum 24 J 3e NMR ofMJS207lfr1 135
60.0 50.0 �.O !
00 N "" '<> "" "" '" "') "" ." ... ..".
39�P 20.0
11\\ � ('t") '¢ "'" U') (/') Q\ f"'l Q \C- t") N r-- oo -,....( .... c) � c\ OO ('f'} � <"l '!"'l
10.0 o
i ! l -"-'7" '�"" :---'-" '-" -" ''-'''�''--- ,.-�
(Millions)
o 1.0 2.0 "
. d
3.0 4.0 5,0 6.0 7.0 8.0 9.0 10.0 1 1.0 12.0 13.0 14.0 IS.O 1 6.0 17.0 18.0 19.0 20.0 21.0 22.0 23.0 24.0 25.0 26.0 27.0 l l lll • • • • ! . , ! ! 1 ! · , .sJ-t...u..l�L1.W ... ..d 1 . ! , l " . ! 1 1 1 1 . ! " " I . , I , I " " I • ..t.J..J..i...u i , t t . I . , • • I • • , ! ! '�.J I , ' I . I • • • . I , ! , . 1 . , [ , 1 , • • • 1 " " I t • • • f t ! 1 . 1 . , . , 1 . , 1 . ' , I..T
) �
1 � ;;: 5: 0' = .... ::t:
.... ' <:> ¢,
�
9" <:>
Q
en
� � en )=0
7.2876 "' .� 00 7.2564 7:'" ..:=,....,,;;;:;��"'"""'======--===�-
'e 7.�354 '-l � r -r f'D . . ¢, � '\ ; 2 ; : 51 ( ;: N til ::c: g; z
o H)
� �:�m >: : J � :::0 5.5989 / L � 5.0284 " , ?, C;i:l 4.9927 / I;> .--� ---"-,.----.,
tv 4.9579 / I I
o \0 -....l � I-' W W ..,. � ¢,
3.8104 '" 3.7820 " , .
3.7546 ./
2.8553 .2.8223 ·2.5522 2.5339
, . 2.3104 2.3013
' 2.2839 '2.2573
!" ��r �o-,
):; '" ¢,
1 .7289 '->,,'.; 1.7024 /-' 1.6758 l .2344 -
¢, -
<::> ..
1
::;> :;:; J, � s;
200.0 1 90.0 ISM
X : parts per Million : Be
i ' 170.0 160.0 150.0
I 140.0 ,13019 120.0 110.0 100.0 90.0 SO.O
i /\ /\ , 1 \
I.f) ClO 1' 0'\ ,., .... 0 0 to-- QO <1\ = '" 0\ '<> 0 M N N - .". "' ... '<> ¢\ oo t"'> t- ..,. <n - ,<> � � �«> � � � tt � ('f') N N """, ,..., _ ,oo.t
Spectrum 26 I 3C NMR ofMJS2097fr1 334
I I I 70.0 60.0 50.0 40.0 30.0 20.0 10.0 0 I
i j!\\ ; \ \
Ii'l .... r- '¢" t- \C � l;: tiH"'-l. C""i t'--C> "'& <:\ :t'--� "'1 2��� '" .,.. "" "M N N N
Co"'; ,"'1 i �.:j
- � �
o s�s�
r I I
I J I I I I i ( I I I j "'��------------------------------------�
.j , I • , I ' , I ' • I ' 10,0 9,0 S,O . . " ,7,0
Ii \\ Qf') � ('f'l. QO 'C ¢\ 'o::!" t.n QC lIl � "I!!" """ _ ¢o ec t-!.� r--! r..!
X : parts per Million : IH
r j�
) ! L
6,0 /\ I i
"' ''' .... r- "' .... ��� "' ." ."
r I I
� , ':C'
5,� 1 ,\ , ,
"' .... '" ,,'''',,::, "' ''' ''' "'''' ''' .i) � �
, I i i . I
4,0 /\
Spectrum 27 IH NMR ofMJS2 1 19fr2346
I
( r I I ( I , I
3,0 .:[, :, . : /I /;! ; 1\\ / ! / " / !
r I
I ' I I ,
2,0 /\ I j • • I • 1,0 o
rJ2 "C ('t> r':> .... "'l = 9 N 00
w (1
� o foot) � C/J tv -...... \0 t:P tv w ..j::>. 0\
X 1 95.7055
II :l '" 't> !l1 is: == �' ... w (")
142.0044
138.1539 135.5257
128.5428 128.3824 128.0539 125.0284
1 16.991 2
77.5997 77.1260 76.6600
49.5688
40.9509
30.6981 29.9035 29.1472 28.1464
2 1 .5684
� o "'" .... '" � ... � --.l ., Q -"""
... '" �
th · o "'"
. .... .... g t;;
"'--., P -: .,-;/ ¢ ,/ /.- .... N <::> "'"
.... .... . g .... <:> 0 "'"
\Q g eo Q -
"'-. "'" / " -.l P , 0::>
'" g th g .... 'Q "'"
� w ." .... ,P :,;::. Q -4
" IV 0 "'"
? 0
0 -'
(Thousands)
o 1M W� �O 4M �o ao �� �o �o ! " ' ! I J ' �-.1-'-L,..J ... l __ L¥lJ-..f.-J-W j j l t l l l ! l l ' I ! I I ! ' ! l t ! , ! ! l l " ' J..J..J..L I I ' I ! ! . ! • . • I " ! ' ! ' ! " ! ' ! ! I ! . " . ! . , ! ! , ! " , I , - e
� Cf) >=0
� -� � � � � l � �
1J). "0 � � -"'I = 9 N \0 ::c:
� o >-I-) � 1J). IV ....... ....... -.....l � ....... VI .......
\C!
� .. 't! .. a � ... is: I: §' 53
7.2454
5.8352
.... P Q
"" b "
<» b -
:-' Q
'" b
5.8123 � -. ,� .. , ' ';
5.7738 /
5.0842 "-, 5.0623 "' ... �. 'Vt: 5.0229
// 'Q
�
i:��;� :?:>� 2.9231 2.6199 �=,
61 -._---. : i:��32 ��' 2.5366 ;/" 2.5101 1 2.3242 N 2.3077 : : :b 2.2747 _._._.c'_-: 1.8470 "7-" 1 .8205
__ 1 .7939 __ ._ : 1.5073 :/:;; : 1.4606 ;/ 1.4139 ./" 1.2417 b -0.8809 � , 0.8571 :...----0.8324
<::>
(Millions)
o to 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 1 1 .0 12.0 13.0 . r l l . j . ' . ! l l t l l ! . I · · , · , · · · · J '..L..J....L..1..U.J..1J....tJ..J-lJ..Jl...LJ.J....W....LJ I . I ( l l l t l ' • • ! " " " " . 1 " " " , • • 1 " 1 1 1 1 1 1 . 1 " • • • " • • 1 " " " " , 1 " " 1 1 1 • • 1 ' ! 1 1 1 1 1 1
�
�"
=, L==
1 (J) )=0
� ...., ::;> til ... 1. S;
E \
�-.--�-==--. c-==� _ _
-j
--l
X : pu1I ,.r MIIm : 13(;
... . ... . ,:.; '.-� -..... : .. ..
o s�s�
1.-.0 I 130.1 !lU ! 110.1 100.0 I ! � :. ; :':, :�, ' , ' 'S.," '-t . • :; ::.. ;;;: ; :: ..:: ....
.- ' .., ... ...
MJI 00.0 ;1' /i\ .Sf:! ��S 1=:""
Spectrum 30 l 3C NMR ofMJS2 1 17fr1 5 1 9
70.0 at !IU I .-.p ' � , 10.1 t I i l \ � I
I ... � �1U;��M��i � � !;it:: G;a " � ������ :tt �