carbonylation as a method for synthesizing organic ... · carbonylation as a method for...
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Carbonylation as a Method for Synthesizing Organic Intermediates and Substrates from Epoxides and Aziridines
Venkata A. KallepalliMichigan State University
Feb. 15th, 2006
Seminar Outline
• Introduction• Carbonylation of Epoxides• Carbonylation of Aziridines• Conclusion• Acknowledgments
� Early Examples
� Scope and Limitations
� Industrial Applications
RCo catalyst
CO / H2R
CHO +R
CHO
Oxo synthesis : Otto Roelen (1938)
Developed by Reppe, Heck, Tsuji
Carbonylation of methanol to acetic acid
CH3OH + CO CH3COOH H = -33kcal/molcatalyst
(Co, Rh, Ir, Ni)
Hohenshutz, H.; Kutepow,N.; Himmele, W. Hydrocarbon Process 1966, 45, 141
2HCo(CO)4 CH3C
O
Co(CO)3
CH3C
O
Co(CO)4
Co2(CO)8H2OCO
CO
CH3OHHI
-H2OCH3I
-CO2
Co(CO)4-H2
CH3Co(CO)4
I-
I-
CH3COI
H2O
CH3COOH
Scope of the Reaction
Carbonylation
Olefins
Alkynes
Dienes
Ketones, Aldehydes, Carboxylic acids,
Esters, Amino acids, Polyketones, Polycarbonates
Alcohols/ PhenolsCarboxylic acids
Organic carbonates
Organic halidesCarboxylic acids,
Keto acids
Esters, Keto esters
Nitro compounds
Isocyanates, Ureas
Carbamates
Amines
Isocyanates, Ureas
Carbamates
Scope of the Carbonylation Reaction
• Economical and Ecologically safe
• Tandem reactions
• Easy access to important precursors and intermediates
Cl
R
CN
R
COCl
R
COOR'
R
NaCN 1.H2O R'OH2. SOCl2
Cl
R
+ R'OH
COOR'
R
catCO
Cl + + CO + ROH COOR
Br
R
+ 2CO + R'2NH
NR'2
R
O
O
Phenyl acetic acid
Capric acid ester
Phenyl Pyruvic amide
Limitations
• High pressure
• High temperature
• Poor selectivity
• Large amount of byproducts
O
O
OH O
Co2(CO)8, CO (3500 psi)
CH3OH, 4 h, 130 oC, 20-40%
Carbonylation Reaction in Industrial Processes
Process Catalyst Company
Methanol to acetic acid Acetylene to acrylic acid Ethylene to propionic acid Butadiene to adipic acid Isobutylphenyl ethanol to Ibuprofen Propylene to methyl Methacrylate Ethylene copolymerization to polyketones
Co2(CO)8
[Rh(CO)I2]-
IrCl3-RuCl3 NiBr2-CuBr2 Ni(OCOC3H5)2 HCo(CO)4 PdCl2(PPh3)2 Pd-pyridyl Phosphine Pd(OAc)2/dppp TsOH
BASF Monsanto BP BASF BASF BASF Hoechst Celanese Shell Shell
Produces more than 8 million tons of carbonylation products
Lactic Acid via Alkoxycarbonylation
O
O
O
MeO OO
OH
OH
OPdCl2(PPh3)2, CO (1000psi)
MeOH, 100 oC, 44 h
81.6%dl - lactic acid
OCOCH3 HPdXL2
OCOCH3
OCOCH3
PdXL2H
CO
OCOCH3
H
PdXL2
O
MeOH
PdX2L2 [ROPdXL2]
[Pd(COOR)XL2] [HPdXL2]
ROH
-HXCO
ROH
(RO)2CO
O
MeO OO
Kiyoshi, K.; Yuiji, O.; Koichi, M.; Sadayuki, M.; Koichi, K.; Nobuyuki, S. Bull. Chem. Soc. Jpn. 1996, 69, 1337-1345
Vinyl acetate Methyl-2-acetoxy propionate
Seminar Outline
• Introduction• Carbonylation of Epoxides• Carbonylation of Aziridines• Conclusion• Acknowledgments
� Stoichiometric Reactions
� Catalytic Reactions
� Theoretical Study of -Lactone formation
� Dicarbonylation Reactions
Carbonylation of Cyclic Ethers
O OO
Co(OAc)2
CO / H2O200 oC, 250 atm 55%
O O O
Co(OAc)2
CO / H2
200 oC, 200 atm35-45%
O
O
OH O
Co2(CO)8, CO (3500 psi)
CH3OH, 4 h, 130 oC, 20-40%
OR
R
n
n = 1,2R = H, Me
R Co(CO)4
OH OR
nN(Cy)2Et
n=2, R=H OO
+
[(Cy)2NHEt]+ [Co(CO)4]-
HCo(CO)4
CO
Heck, R. F. J. Am. Chem. Soc. 1963, 85, 1460
Reppe, W.; Kroper,H.; Pistor, H. J.; Weissbarth, O. Justus Liebigs Ann Chem. 1953, 582, 87
Khumataveeporn, K.; Alper, H.; Acc. Chem. Res. 1995, 28, 414
Eisenmann, J. L.; Yamartino, R. L.; Howard, J. F. J. Org. Chem. 1961, 26, 2102
Carbonylation of Epoxides
• Why Epoxides?
O
R
O
O
O
R
R
O
CO, [M]
a
b
R = aryl, vinyl
R = alkyl, ether, ester, amide
• Efficient way to -Lactones
• Availability of the Epoxides
• Reactivity of the Epoxides
Tokunaga, M.; Larrow, J. F.; Kakiuchi, F.; Jacobsen, E. N. Science 1997, 277, 936-938
Why -Lactones?
OO
R' R
NHR2''
NaN3
(R = CH2R')
MgBr2
1.LDA2.R''I
R''2N R
O OH
R'
R'
R
+ CO2
LnM-OR
O
O
R'
R
n
HO N3
R'
RO
O
R''
R'R
O
OO
R' R'
Getzler, Y. D. Y. L.; Schmidt, J. A. R.; Coates, G. W. Journal of Chemical Education 2005, 82, 621-624
Natural -Lactones
OO
C6H13
OO
NHCHO
OO
C6H13
H2NO
O
O NHCOCH3
Lipstatin Esterastin
O
H
H
H
O
OCOCHCH2(CH3)2
O
O
O
O
O
O
Spongiolactone Guaiagrazielolide
Pommier, A.; Pons, J. M. Synthesis 1995, 729-744
Photocarbonylation of Epoxide
R12R
3R
R4
O
Fe O(CO)3
R12R
3R
R4
O
Fe O(CO)3
syn-isomer anti-isomer
Frohlich, K.; Ring, H.; Aumann, R. Angew. Chem. Int. Ed. Engl. 1974, 13, 275
Annis, G. D.; Ley, S. V. J. Chem. Soc. Chem. Commun, 1977, 581
Annis, G. D.; Ley, S. V.; Self, C. R.; Sivaramakrishnan, R. J. Chem. Soc., Perkin Trans. 1 1981, 270
O
C6H13 C4H9
OO
O
NHCHO
Valilactone
OC9H19
OH
O
Malyngolide
Isolated : Streptomyces albolongus
Esterase inhibitor
Isolated : Lyngbya majuscula
Antibacterial agent
O R12R
3R
R4
O R12R
3R
R4
Fe(CO)4
R12R
3R
R4
O
Fe O(CO)3
R12R
3R
R4
O
O
+O
O
R1
2R
3R
R4
Fe(CO)5
C6H6, hv, -CO
CeIV
Synthesis of Valilactone
Bates, R.W.; Fernandez-Moro.; Ley, S. V. Tetrahedron Lett1991, 32, 2651
Bates, R.W.; Fernandez-Moro.; Ley, S. V. Tetrahedron 1991, 47, 9929
C4H9 C5H11
OH
Zn/Cu/Ag, MeOH-H2O
50 oC. 90%
C4H9 C5H11
OH
VO(acac)2, tBuOOH
CH2Cl2, 0 oC to r.t., 73%
C4H9 C5H11
OHO
Fe2(CO)9, THF. 80%
C4H9 C5H11
OHO(OC)3Fe
O
C5H11
C4H9
OHO(OC)3Fe
+1..
4
O
C4H9 C5H11
OO
OH
CAN, EtOH,
r.t. 26%N-Cbz-L-valine, DCC,
CH2Cl2, 0 oC, then DMF,DMAP, r.t., 56%
H2/Pd/C, THF, then AcOCHO, CH2Cl2, 62%
O
C6H13 C4H9
OO
O
NHCHO
A
B
Synthesis of Malyngolide
Horton, A. M.; Ley, S. V. J. Organomet. Chem. 1985, 285, C17
OH
C9H19
O
O
Fe(CO)3
O
C9H19
OH
O OC9H19
OH
+O OC9H19
OH
O OC9H19
OH
O OC9H19
OH
OH
C9H19
BuOOH, VO(acac)2
benzene, 10 mins
COOMe
OH
C9H19
KHSO4, toluene, 48 h; then DBU, r.t., 24 h,
then LiAlH4 in ether added at 0 oC
Fe2(CO)9, THF
CO(300atm), 90 oC, 24 h
PtO2/H2, MeOHPtO2/H2, MeOH
LDA, -78 oC, H+ work-up
69% conversion
AB
Catalytic Carbonylation of Epoxides
O
Ph
OO
Ph2-3 mol% RhCl(CO)(PPh3)2
(67%)
CO (400psi)
Ph
CH2OMOM
(44%)
+
Aumann, R.; Ring, H.; Angew. Chem. Int. Ed. Engl. 1977, 16, 50
Kamiya, Y.; Kawato, K.; Ohta, H. Chem. Lett. 1980, 1549
Shimizu, I.; Maruyama, T.; Makuta, T.; Yamamoto, A. Tetrahedron Lett. 1993, 34, 2135
O
Ph CH2OMOM
OO
Ph CH2OMOM5 mol% Pd2(C4H7)2Cl2CO (30atm), EtOH, r.t.
i-Pr2NEt, NaBrmaleic anhydride
(14%)
O2 mol % [Rh(COD)Cl]2 O
O CO (150atm), CCl4, 70 oC, 50 h
(75%)
Carbonylation of Epoxides:
O+ CO
cat + LA2 - 4 mol%
80-110 oC, 24 - 48 h OO
cat
[PPN][Co(CO)4] BF3 . Et2O
[PPN][Co(CO)4] B(C6F5)3
LA
Drent, E.; Kragtwijk, E. Eur. Pat. Appl. EP 577206
Lee, J. T.; Thomas, P. J.; Alper, H. J. Org. Chem. 2001, 66, 5424-5426
(PPN = Ph3P N PPh3)
OO
O
Co2(CO)8, CO (60atm),
75 oC,6 h
N
OH
93% conversion90% selectivity
Substrate Scope of [PPN][Co(CO)4] Catalyst
Lee, J. T.; Thomas, P. J.; Alper, H. J. Org. Chem. 2001, 66, 5424-5426
substrate LA product (% isolated yield)
O
3
OO
O OO
Cl
O
Ph
O
HO
O
PrO
O
i
O
O
3
Cl
BF3 . Et2O
BF3 . Et2O
BF3 . Et2O
BF3 . Et2O
BF3 . Et2O
BF3 . Et2O
B(C6F5)3
B(C6F5)3
OO
OO
HO
- (no reaction)
PrOi
OO
O
OO
O
(66)
(83)
(63)
(57)
(86)
(20)
(24)
substrate LA product (% isolated yield)
(PPN = Ph3P N PPh3)
Salen Based Catalysts
Getzler, Y. D. Y. L.; Mahadevan, V.; Lobkovsky, E. B.; Coates, G. W. J. Am. Chem. Soc. 2002, 124, 1174
catalyst time yield(%)R1 R2
[PPN][Co(CO)4/BF3.Et2O
[nBu4N][Co(CO)4]
1
H
H
H
H
Me
Me
Me
Me
1 Me Me
24
16
16
1
1
77
0
6
95
83
[Na][Co(CO)4]
O O1-2 mol% catalyst,
CO (900psi)
50o - 80 oC
O
R1R2
R1R2
tBuO
NN
OButBu But
Al+t
Co(CO)4-
L=THFL
L
1
O O1mol% 1, CO (880psi)
50 oC, neat, 1h 95% (96% ee)
O
Stereochemistry of carbonylation
O+ CO
OO
1
racemic
O+ CO
OO
1
racemicracemic
1
tBuO
NN
OButBu But
Al+t
Co(CO)4-
L=THFL
L
tBuO
NN
OButBu But
Al+t
Co(CO)4-
L=THFL
L
2
Getzler, Y. D. Y. L.; Mahadevan, V.; Lobkovsky, E. B.; Coates, G. W. Pure Appl. Chem. 2004, 76, 557
O+ CO
OO
2
racemic
+O
O
Enantiomerically-enriched44 % ee
LA Promoted Carbonylation Mechanism
Getzler, Y. D. Y. L.; Mahadevan, V.; Lobkovsky, E. B.; Coates, G. W. J. Am. Chem. Soc. 2002, 124, 1174Molnar, F.; Luinstra, G. A.; Allmendinger, M.; Reiger, B. Chem. – Eur. J. 2003, 9, 1273-1280.Getzler, Y. D. Y. L.; Mahadevan, V.; Lobkovsky, E. B.; Coates, G. W. Pure Appl. Chem. 2004, 76, 557
O
M+Ln
Co(CO)4
O Co(CO)4LnM
O Co(CO)4
O
LnM
CO
[LnM][Co(CO)4]
OO
O
Theoretical Study of -Lactone Synthesis
• Single-Site Catalysts
• Multisite Catalysts
O O catalyst, CO O
� Co, Rh, Pd catalysts, Co[CO4-]
� No low energy pathway for ring opening� -allyl complex formation is a must
� [Lewis acid][Co(CO)4]
Molnar, F.; Luinstra, G. A.; Allmendinger, M.; Reiger, B. Chem. – Eur. J. 2003, 9, 1273-1280.
• Multisite Catalysts
� [Lewis acid][Co(CO)4]� Opens a low energy pathway for trans opening� Effect of Lewis acid (BF3, Me3Al,
Et2Al+. diglyme & Me3Al/Co2(CO)8)� CO insertion & uptake
Co R
OOC
LA
CO insertion
(CO)3
(OC)3Co
O
R
O
LA
(OC)4Co
O
R
O
LACO uptake
Porphyrin Based Catalyst
N
NN
N
Cr+
O
O
Ph
Ph
Ph
Ph
Co(CO)4-
3
tBuO
NN
OButBu But
Al+t
Co(CO)4-
L=THFL
L
1
O
R1 R2
O
R1 R2
Ocatalyst, CO (900 psi)
neat, 60 oC, 6 h
Schmidt, J.A.; Mahadevan, V.; Getzler, Y. D. Y. L.; Coates, G. W. Org. Lett. 2004, 6, 373
R1 R2
substrate:catalyst
yield (%)
H 350:1
H
H
H
CH3
CH3 75:1
>99 40
>99 0
>99 40
>99 30
>99 74
56 20
nBu
H2C=CH(CH2)2 250:1
tBu 800:1
TBDMSOCH2
trans-CH3
cis-CH3
400:1
75:1
3 1
Highly Active and Versatile Catalyst
N
NN
N
Cr+
O
O
Co(CO)4-
substrate substrate/4 product yield
O OO
3500 > 99%
O
3
O
3
O
4500 > 99%
O
9
10000O
9
O
> 99%
Bu
O
t5000
Bu
O
t
O
> 99%
O3500 O
O
> 99%
O450 O
O
88%
Schmidt, J. A.; Lobkovsky, E. B.; Coates, G. W. J. Am. Chem. Soc. 2005, 127, 11426
4
N
NN
N
Cr+
O
O
Ph
Ph
Ph
Ph
Co(CO)4-
3
Expanding the Range of Glycidyl Ethers
substrate substrate/4 product yield
MeO
O
BuMe2SiO
O
PhH2CO
O
O
O
O
O
t
O
750>99%
MeO
OO
2500
1800
250
250
BuMe2SiO
OO
t
PhH2CO
OO
O
O
O
O
O
O
O
>99%
>99%
>99%
88%
4
Schmidt, J. A.; Lobkovsky, E. B.; Coates, G. W. J. Am. Chem. Soc. 2005, 127, 11426
N
NN
N
Cr+
O
O
Co(CO)4-
Esters and Amides are Tolerated
Schmidt, J. A.; Lobkovsky, E. B.; Coates, G. W. J. Am. Chem. Soc. 2005, 127, 11426
substrate substrate/4 conditions product yield
O
O
O
30040 oC
6h O
O
OO
> 99%
Ph O
O
O
25040 oC
6h Ph O
O
OO
97%
Pr O
O
O
n
23500
60 oC6h Pr O
O
n
2
OO
> 99%
Pr0
O
O
n
150060 oC
6h Pr0
O
n
OO
> 99%
Me2N O
O
O7
75 60 oC6h Me2N O
O7
OO
> 99%
Rearrangement of -Lactone to -lactone
substrate substrate/4 conditions product yield
O
O
O
300 40 oC6h O
O
OO
> 99%
Ph O
O
O
25040 oC
6h Ph O
O
OO
97%
O
O
O
55060 oC24h
> 99%
Ph O
O
O
250 60 oC24h
> 99%
O
O O
O
Ph O
O O
O
Schmidt, J. A.; Lobkovsky, E. B.; Coates, G. W. J. Am. Chem. Soc. 2005, 127, 11426
Rearrangement of -Lactone to -lactone
PrO
OO
n
PrO
O
n O
O
4+
OO
O 4+
Pr
O
n
O
O
O4
OPrn +
OO
OPr
O
4+Co(CO)4-,
CO
Schmidt, J. A.; Lobkovsky, E. B.; Coates, G. W. J. Am. Chem. Soc. 2005, 127, 11426
N
NN
N
Cr+
O
O
4+
Bicyclic -Lactones
Schmidt, J. A.; Lobkovsky, E. B.; Coates, G. W. J. Am. Chem. Soc. 2005, 127, 11426
O
O
O
O
O
O
substrate substrate/catalyst product yield
O
O
O
> 99%
> 99%
> 99%
57%
100
250
100
100
O OO
Mechanism of Stereoretention(OEP)CrO
+
-Co(CO)4
(OEP)CrO Co(CO)4
OO
Co(CO)4(OEP)Cr
[(OEP)Cr][Co(CO)4]
CO
OO
O
(OEP)CrO Co(CO)4
Schmidt, J. A.; Lobkovsky, E. B.; Coates, G. W. J. Am. Chem. Soc. 2005, 127, 11426
OEP = octaethyl porphyrin
Dicarbonylation of Epoxides
O
Ph RO
O
HO
Ph R
HCo2(CO)8, CTAB, MeI
NaOH (0.5M), C6H6,r.t.., CO (1atm)
1 (R=H)
Alper, H.; Arzoumanian, H.; Petrignani, J.F.; Maldonado, M. S. J. Chem. Soc., Chem. Commun. 1985, 340
Mechanism of Dicarbonylation
PhO Me
O
O Co(CO)4
PhO Me
O
HO Co(CO)4
PhO Me
O
HO
O
Co(CO)4
Co(CO)4- MeI Co(CO)4 Co(CO)4Me Me
O
PhO Me
O
Co(CO)4
CO
CO 1
CO
O
O
HO
Ph
Dicarbonylation of Epoxides
O OO OO
O1 mol% 1, CO (880psi)
1 h, 50 oC, neat
O.45 mol% 1, CO (200psi)
24 h, 55 oC, toluene
99% ee
[LnAl]+[Co(CO)4]-
LnAlO Co(CO)4
O
LnAlO
O
Co(CO)4
O
OO
CO
OO O
Getzler, Y. D. Y. L.; Kundnani, V.; Lobkovsky, E. B.; Coates, G. W. J. Am. Chem. Soc. 2004, 126, 6842
Proposed Mechanism
Seminar Outline
• Introduction• Carbonylation of Epoxides• Carbonylation of Aziridines
• Inversion of Stereochemistry
• Effect of EWG groups
• Bimetallic catalysts
Carbonylation of Aziridines
N
R
R'
N
N
O
R
R
R'
O R'
CO, [M]
a
b
N
Pri
PhMe
NO
PhMe
Pri
[Rh(CO)2Cl]2
CO, 20atm90o, C6H6
N
Et H
CH2CH2PhN
Et H
OPhH2CH2C
Co2(CO)8 (8 mol%)
DME, CO (33 atm)100 oC, 24 h
Ph ON
Boc
Ph O
NBoc
Pd NO
OPh
Boc
Pd2(dba)3. CHCl3
PPh3, CO, 1 atmr.t., 3days
(51%)
CO
N
R
Pd(PPh3)4
N PdL2R
NOR
(55-83%)
CH2Cl2, RT, CO,1atm
CO
Hamel, N.; Alper, H. Tetrahedron Lett 1987, 28, 3237.Calet, S.; Urso, F.; Alper, H. J. Am. Chem. Soc. 1989, 111, 931.Spears, G. W.; Nakanishi, K.; Ohfune, Y. Synlett 1991, 91.Marcelo, E. P.; Alper, H. J. Am. Chem. Soc. 1996, 118, 111.
Inversion of stereochemistry
N
R2 R3
H H
R1
R2 H
H R3
OR1
Co2(CO)8 (8 mol%)or NaCo(CO)4
DME, CO (33 atm)100 oC, 24 h
PhCH2CH2 Et H 94
PhCH2 Et H 64
p-MeOPh t-Bu H 50
i-Pr H Ph 42
i-Pr Me Ph 94
R1 R2 R3
isolatedyield
Co(CO)4
N Co(CO)4
R2 R3
R1
N
R2 R3
R1
Co(CO)4
O
N
R2 R3
H H
R1
CO
N
R2 H
H R3
OR1Marcelo, E. P.; Alper, H. J. Am. Chem. Soc. 1996, 118, 111.
Effect of EWG Substituents
N
Me
N
Me
O
Co2(CO)8 (8 mol%)
DME, CO (33 atm)100 oC, 24 h
Ph PhO
O+
NO
Ph
O
Me
(55%) (37%)
SET Mechanism:
Marcelo, E. P.; Alper, H. J. Am. Chem. Soc. 1996, 118, 111.
Co(CO)4-
N
MePh
O
Co(CO)4 + N
MePh
O-
SETCo(CO)4
+Me
C NPh
O-H
H
MeC N
Ph
O-Co(CO)4
HMeC N
Ph
O-
H
Co(CO)4O
MeC N
H
Co(CO)4O
-
Ph
O
N
Me
H
O Ph
O
Substituents at 2-Position
N
RPh
Ph
N Ph
Ph R
O
Co2(CO)8 (8 mol%)
DME, CO (500 psi)100 oC, 14 h
cis
cis
cis
Aziridines
Stereochemistry
R ß-Lactams
Stereochemistry Yield(%)
COOCH3 - -
COCH3 - -
CHO - -
cis CH2OH trans 79
cis CH2OTBDMS trans 96
cis
cis
CH2OAc trans 86
CH2NH2 trans 68
trans
trans
CH2OH - -
CH2OTBDMS cis 40
Davoli, P.; Forni, A.; Moretti, I.; Torre, G.; Prati, F. Tetrahedron 2001, 57, 1801-1812.
Effect of Intramolecular H-Bonding
Davoli, P.; Forni, A.; Moretti, I.; Torre, G.; Prati, F. Tetrahedron 2001, 57, 1801-1812.
N
H3C
Ph
Co2(CO)8 (8mol%)
DME, CO (500psi)100 oC, 14h
OH
O
HN
Ph
O
Mechanism
CO
N
H3C
Ph
OH
N H
O(OC)4Co
PhO
HN
(OC)4Co
O
OO
HN
Ph
Ph
[Co(CO)4]
Bimetallic Catalysts
tBuO
NN
OButBu But
Al+t
Co(CO)4-
L=THFL
L
Ti+O
O[Co(CO)4]-
1
2
Mahadevan, V.; Getzler, Y. D. Y. L.; Coates, G. W. Angew. Chem. Int. Ed. 2002, 6, 2781
N
Ph
N
Ph
N
Ph
TBSO
+_
1
2N
O
Ph
90
50
1
2
NO
Ph
+_
80
<5
1
NO
Ph
TBSO
+_
TBSO
+_
Ph
O
19
..
1
95
Substrate Catalyst Product Yield[%]
Conclusions
• Mild and Efficient route to Lactones and Lactams
• Access to Bicyclic systems
• Mechanistic study helps in the design of new catalysts
Acknowledgement
• Dr. Smith• Dr. Wagner• Smith’s Group
Abbas, Aparajita, Edith, Sulagna, Washington
• Doug, Kapil, Sandeep, Nicki, Gwenn, Sue