diastereoselective diels–alder reactions: chiral...
Post on 28-Dec-2019
7 Views
Preview:
TRANSCRIPT
Electron Rich Substituents have lone pairs (OR, NR2, SR, SO2R)Electron Poor Substituents: SiR3 (electropositive)
Based solely on electrostatic considerations
Mick DartEvans Group SeminarTues. Jan. 18, 1994
1. Diels Alder reactions2. Halogenation and related electrophilic additions3. Reactions of allylsilanes4. Hydroborations5. Osmylations
Diastereoselective Attack ofElectrophiles on Chiral Olefins
D. Jones, J. C. S. Chem. Comm. 1980, 739.
■ Other dienophiles also give adducts derived from endo addition syn to the hydroxyl
anti
syn
DienophileX
SynAnti
Electron RichElectron Poor
Hehre's Proposal:
■ Opposite diastereofacial selectivity is observed with acrolein.
(73%)
■ Stereocontrol: A(1,3) strain
Trost, J. Org. Chem, 1989, 54, 2271-2274.
Diastereoselective Diels–Alder Reactions: Chiral Dienes
Diastereoselection 91 : 9
Diastereoselection >95 : 5
Kahn & Hehre, J. Am. Chem. Soc. 1987, 109, 663-666.
(99%)PhN
O
O O
O
Me
H
H
O
NPh
Me
OHH
HOH
O
H
H
Me
H
O
H
R
X
H
Me
Me
OH O
O
OO
O
O
Me
Me
OHH
H OH
Me
01-Diels-Alder 3/19/02 2:03 PM
Also see A. Kozikowski, J. Am. Chem. Soc. 1987, 109, 5167-5175.
Allylic Ether
Allylsilane
Favored diene conformers in reactions with acetylenic dienophiles
Dienophile
■ Rationalization for diastereofacial selectivity:
Fleming, JCS Perkin Trans I, 1989, 2023-2030.
Diastereoselective Diels–Alder Reactions: Chiral Dienes
Diastereoselection 82 : 18
Diastereoselection 12 : 88R. Franck, J. Am. Chem. Soc. 1988, 110, 3257
Dienophile
Dienophile Dienophile
Dienophile
PhH, rt
PhH, 60 °C
10 days
2 days
(96%)
(90%)
2 days
PhMe, 100 °C
Dienophile
Dienophile
Dienophile
R. Franck, J. Am. Chem. Soc. 1988, 110, 3257 Diastereoselection 27 : 73
Diastereoselection >99 : 1Fleming, JCS Perkin Trans I, 1989, 2023-2030.
PhMe, 100 °C
2 days
(72%)
(62%)
See Houk & Co-workers Science, 1986, 221, 1108-1117.
anti
outsideinside
Dienophile
Me
H SiMe2Ph
Me
PhN
O
O
NPh
O
O
H SiMe2Ph
Me
MeH
HH
NPh
O
O
H OSiMe3
Me
MeH
HHH H
HMe
Me
OSiMe3H
O
O
NPh
SiMe2Ph
Me
H H
HMe
Me
Me
SiMe2PhH
O
O
NPh
O
O
PhN
Me
OSiMe3H
Me
HMe
H Me
OSiMe2 Me
HMe3SiOMe
Me
Me H
OSiMe3H
Me
PhMe2Si Me
Me
Me3SiO H
Me
Me
OSiMe3H
Me
Me
H OSiMe3
Me CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
H SiMe2Ph
Me
Me
Me
H
H Me
SiMe2Ph
CO2Me
CO2Me CO2Me
CO2Me
Me
H OSiMe3
Me
Me
H H
MeH
Me
Me
OSiMe3H
SiMe2Ph
H
Me
Me
SiMe2PhH
Me
CO2Me
CO2Me
CO2Me
CO2MeH
SiMe2Ph
H
Me
SiMe2PhH
Me
Me
PhMe2Si
Me
02-Diels-Alder 3/19/02 1:59 PM
A preference for "inside alkoxy"is observed in these cyclizations
BA
low yield due to δ-lactone formation
Gauche A is now moredestabilizing than gauche B
+
I2, HOH/THF
HCO3–
Ratio >95 : 5 (49%)
+A B
How can the above results be rationalized?
Chamberlin, J. Am. Chem. Soc. 1983, 105, 5819-5825.
K2CO3MeOH
Epoxidation Ratio = 3 : 97Lactonization Ratio = 96 : 4
t-BuOOHVO(acac)2
Gauche B is more destabilizing than gauche A
+
Ratio96 : 4 (85%)
HCO3–
I2, HOH/THF
+
R = H
R = Me
A(1,2) strain
95 : 5 49
■ Kinetic conditions: 3 equiv I2, aq Na2CO3, Et2O, 0 °C
■ Protection of the hydroxyl group (TBS or Ac) does not affect selectivity
■ Iodolactonization of allylic alcohols
75 : 25 9 : 91
(cis : trans)
NIS, CHCl3, 25 °C3 equiv I2, MeCN, O °C
KineticThermodynamic
Conditions
Bartlett, J. Am. Chem. Soc. 1978, 100, 3950-3952.
Iodolactonization
Yield (%)SelectivityMajor ProductSubstrate
85
7481
4194
66
R = HR = Me
95 : 5
87 : 1390 : 10
93 : 7
77 : 2342 : 58
R = HR = Me
Chamberlin, J. Am. Chem. Soc. 1983, 105, 5819-5825.
■ Bartlett's "thermodynamic conditions" produced complex mixtures
I
HO
OO
OO
HO
IMe
Me
R
R
Me OH
HO
O
-O2CCH2
HO H
O
C HCH
Me
HO
I
Me
O H
HO
O
II
O
HO
HO
C
IH
OH
CMe
H
R
R
Me
H
HO
CH2
Me
OH
Me
-O2C
O
RO
OH
MeHO
O
O
HO
OH
OH
HO
OO
I
Me
O
Me
I
O
Me
HO
O
O
OO
Me
OH
Me
RO
O
-O2CCH2
HO
Me
Me
HO H
CMe
CH
Me
I
O Me
HO
O
I I
O
HO
MeO
Me
HO
C
I
CMe
HMe
H
CH2-O2C
O
MeO
Me
OH
Me
Me
IH
I
HO
O
OOMe
OH
Me
MeO
O
O
O
OH
O
I
Me
03-Iodolactonization 3/19/02 2:00 PM
■ Place the medium size group (–OH) outside and the small group (–H) inside
■ Other conditions: I2, THF/phosphate buffer; I2, THF, aq Na2CO3 provide 1,3–diols in very high selectivity
Model for Stereoinduction?
minormajor
Gauche B is more energetically destabilizing than gauche A
I2, AgOAc+ +
–OAc AcO–
BA
AB
H2O
++I2, AgOAc
Gauche A is now more destabilizing than gauche B
OH2
Ratio 80 : 20 perfect regioselectivity
HCO3–
I2, HOH/THF Poor regioselectivity affordsa mixture of products
Evans, Kaldor, Jones, J. Am. Chem. Soc. 1990, 112, 7001.
Chamberlin, Tetrahedron 1984, 40, 2297-2302.
Diastereoselection 96 : 4
I2, THFaq KH2PO4
Cytovaricin Synthesis
■ High selectivities are also observed with allylic ethers (OMe, OBn, OTBS)
■ Prevost conditions: 2 equiv I2, 2 equiv AgOAc, THF, –78 →0 °C
94 : 6
98 : 2
95 : 5
80 : 20
78
90
85
Substrate Major Product Selectivity Yield (%)
Iodo diol formation from allylic alcohols
■ Analysis: D. A. Evans, Chem. 115, Lecture 23, Dec. 16, 1993
HO H
R
CH
H
OAc
I
OH
R'R
OH
CMe
I
R'
HO H
R
CMe CH
H
I
I
Me
OH
Me
OH
Bu
Bu Me
R
Me
OH
TIPSO
Me
Bu
OH
Me
OH
Me
OAc
R
Bu
R'
OH
I
OH OH
Bu I
Me
OAc
C C
IH
OH
Me
OH
Bu
OAc
OH
Me
R RHO
OH
R
OH
OH
Me
I
OH
R
Me
Me
Bu
Bu
OH
I
I
I
I
Me MeHO
OAc
TIPSO
OH
R'
HH
R
HO
C C
IHO
HHR'
R
H
04-Iododiol formation 3/19/02 2:00 PM
■ "The presence or absence of an internal nucleophile acts to determine the stereochemical outcome of the reaction by modifying the nature (timing) oftransition state.
■ Onium ion formation is rate determing in the addition reactions■ π–complex cyclizes if R contains a Nu and its formation is rate determining
For a review of the halogenation reaction see: Andy Ratz, Evans Group Seminar,Synthetic and Mechanistic Review of Electrophilic Halogenation, May 7, 1992.
For a review of elctrophilic induced olefin cyclization reactions see:G. Cardillo & M. Orena, Tetrahedron 1990, 46, 3321.
■ "Facial preferences in electrophilic addition reactions are not invariant with respect to the location of the transition state along the reaction coordinate."
Chamberlin & Hehre, J. Am. Chem. Soc. 1987, 109, 672-677.
-
I2
I2
OH2
cis : trans 95 : 5
ratio 99 : 1
I2
I2
H2O
■ A complete turnover in olefin diastereofacial selectivity is observed when adding internal and external nucleophiles
Chamberlin & Hehre's Rationalization
For electrophiles that react via onium intermediates (I2, Br2, Hg(OAc)2, PhSeCl),the major diastereomer from electrophile-induced cyclization is opposite to thatobserved in the analogous intermolecular electrophilic addition.
General Observation:
■ Analysis of the stereoselectivity of electrophilic addition to chiral olefins:
1. Relative abundances of conformational minima2. Relative reactivities of the available forms3. Stereoselectivies of the individual conformers
■ Change in diastereoselectivity is a consequence of a change in the rate-limiting step
● Addition reactions: Formation of an onium ion intermediate(subsequently trapped by a Nu from the medium)
● Cyclization reactions: Intramolecular attack on a ππππ–complex (not an onium ion)
+
+
Nu
Nu
Disfavored π–complex
Favored π–complex Disfavored iodonium ion
Favored iodonium ion
Cyclization product
Addition product
Favored ground-state conformer
More reactiveground-state conformer
Hehre's Analysis
Houk: Argument for the "inside alkoxy effect" in π–complex formation
OO
HO
OH
MeBu
OH
I
Me
IH
I
OH
Bu Me
OH
HI
Me
HO
OO
Bu
HHO
OH
Bu Me
Me
OH
HO
O
OO
Me
OH
H
I2
H
O
O
H
H
R
H
OH
Me Me
OH
H
R
H
I
HO
Me
Me
IH
OH
MeBu
OH
I
Me
HR
HO
H
H H H
H
H
HO
R
H
MeMe
H
R
HO
H
H H
H
OH
RH
MeI
I2
05-Iodolact/Hehre 3/19/02 2:00 PM
D. A. Evans, Chem. 115, Lecture 23, Dec. 16, 1993
Diastereoselective Functionalization of (E) Allylic Alcohols
■ Halogenation
■ Oxymercuration
■ Hydroboration
■ Sulfenylation
At least 3 major productsH2O2
ThexylBH2
Ratio = 99 : 1 (40%)
PhS–Cl
Me2ZnTiCl4
+
Ratio = 50 : 50 (77%)
Me2ZnTiCl4
PhS–Cl
+
Reetz, Angew. Chem. Int. Ed. 1987, 26, 1028-1029.
minormajor
Gauche B is more energetically destabilizing than gauche A
syn : anti = 80 :20Chamberlin, Tetrahedron 1984, 40, 2297-2302.
Hg(OAc)2
I2, AgOAc
+ +
–OAc AcO–
BA
Hg(OAc)2
R'OH
Oxymercuration of Acyclic allylic alcohols:
NaBH4
R R'OH Ratio
-Et HOH 76 : 24
yield
65%72%93 : 07MeOH-Et
-Ph HOH 88 : 12 66%
70%98 : 02HOH-tBu
Giese, Tet. Lett. 1985, 26, 1197
Hg(OAc)2
NaBH4
HOH
Hg(OAc)2
syn
syn : anti = 77 : 23
O-acetate participation will turn over the stereochemical course of the rxn
Iodohydroxylation of thesesubstrates is not regioselective
+
+ +
+
FavoredDisfavored
■ Hehre's model could be invoked to explain turnover in π–facial selectivity
O
H RL
CH
C
n-Bu
OH
Me
OAc
I
OH
H
H
Hg
X
R'
O
R
H
C
Hg
X
H
HC
H
RL
O
R
OH OH
R
R
C
Hg
RL
H
HCH
OR'
HgOAc
OR'
R
H
Me
OH
X
C
HgH
X
CH
H
OH
OH
H
n-Bu
R' HO
RL
OH
RL
HgOAcHgOAc
Me
OH
OR'n-Bu
RL
HO
OH
OH
OH
RL
OR'
HgOAc
O
R
OR
Me
MeRL
OR
Et
OR
RL
Me
OR
HO
OBz
H
OH
EtMe
OBzOBz
Et
CH
CH
Me
Hg
X
RR R'
OH
I
OAc
C C
IH
S
Ph
C
H
CEt
H
H
MeO
Me
Me
Me
SPh
Me
TBSO
Et
OMe
Me
Me
OTBS
Me
TBSO
Me
SPh
Me
Me
MeO
Me
SPh
Et
Me
Me
OH
R'
HH
R
HO
C C
IHO
HHR'
R
H
n-Bu
06-Oxymercuration 3/19/02 2:01 PM
Scott J. Miller Evans Evening Seminar, "The Chemistry ofAllylsilanes and the β Silicon Effect," Dec 11, 1990, p 45.
Path A Path B
Paddon-Row, Rondan, and Houk JACS 1982 104, 7162.
+ +
El+ El+
■ If A = H, then Path B can compete
■ If A ≥ Me, then Path A dominates due to A(1,3) strain
Stereochemical Model For Electrophilic Attack on Allylsilanes
Model assumes: 1. Electrophilic attack anti to the silyl moiety2. The silyl group is the "large" substituent
Electrophilic Attack on Allylsilanes
mCPBA
MeiPrPH
61 : 39>95 : 05 89 : 11
R Ratio
RatioR
58 : 42>95 : 05 91 : 09
MeiPrPH
AlMe3
OsO4
MeiPrPH
34 : 66 67 : 33 92 : 08
R Ratio
CH2I2
■ Epoxidation
■ Cyclopropanation
■ Osmylation
The products on the leftcorrespond to attack by Path A
■ Larger R groups result in higher selectivity
■ The size of R is more important in locking the substrate into the conformation leading to Path A than in shieldieng the El+
Fleming, JCS Perkin Trans I, 1992, 3303-3308.
El
C
R
SiR3R'
A
HR
PhMe2Si
MeR
SiR3
C H
H
C
El
CR'
H R
SiR3
CHA
R'
R
El
R R'
Me R
A
Me
PhMe2Si
C H
PhMe2Si
O O
PhMe2SiPhMe2Si
MeRMeRR
R
HR
SiR3
CH
Me
PhMe2Si
PhMe2Si
MeR
C A
R Me R Me
PhMe2Si
R'
PhMe2Si
OH
OH
OH
OH
A El A
A
R R'
SiR3
R'
07-Allylsilanes 3/19/02 2:01 PM
K. N. Houk, M. N. Paddon-Row, & Co-workers, Tetrahedron 1984, 40, 2257-2274.
Assume OH (OR') = Rm and results are consistent with the model
W. C. Still & J. C. Barrish, J. Am. Chem. Soc. 1983, 105, 2487.
BH3•THF
9–BBN
H2O2
OR'
OHOHOTMSOAcOH
nBuiPrnBunBunBu
92 : 08 96 : 04 91 : 09 88 : 12 42 : 58
SelectivityR
R2BH
M. M. Midland & Co-workers, J. Am. Chem. Soc. 1983, 105, 3725.
H2O2
R2BH
Dave Evans, Chem 115, Lecture 22, Dec 14, 1993
BH3
H2O2H2O2
■ A turnover in diastereofacial selectivity is sometimes observed using BH3
Favored product fordialkyl borane reagents
H2O2H2O2
R2BH
WorseBad
■ Hydroboration of allylic alcohols (ethers)
Selectivity
50 : 50 80 : 20 93 : 07 96 : 04
BH3•DMSThexylBH29–BBN(Chx)2BH
Diastereoselective Hydroboration Examples
A Model for Diastereoselective Hydroborations
OH
Me
RM
OH RL
R
OR'
RL
RM
Me
B
H
B
HHH
Me
RM
Me
C
H
RL
H
CMe
C
Me
OR'
RL R ROHRM
H
OR'
Me
OH
H
H
RL
RM H
CMe
C
C
B B H
H
H
Me
HRM
RL
RMRL
RM
Me
R RR R
Me
RM
RL RLOH
RM
Me
OH
H
H
H
CCH
H Me
H
RL
Me
H
H
MeMe
H
H
MeH H
OH
HMe
H
H
MeOH
08-Hydroboration Models 3/19/02 2:01 PM
I. Paterson & J. ChannonTetrahedron Lett., 1992, 33, 797-800.
BH3•THF unexpectedly provided theanti isomer in high selectivity
5
synanti
74%89%
yield
95 : 05>95 : 05
9-BBNBH3•THF
anti : syn
anti : syn
9-BBNBH3•THF
85 : 15 05 : 95
yield
70%84%
anti syn
80%99%
yield
82 : 1817 : 83
(Chx)2BHBH3•DMS
anti : syn
synanti
The sense of asymmetric induction is completely turnedover in Andy's reaction when using R2BH↔BH3
■ Erythronolide synthesis: Annette Kim
Diastereoselection 93 : 7
THF, 0 °C→rt 12 h
3 ThexylBH2
■ Lonomycin synthesis: Andy Ratz
Diastereoselective Hydroborations
BH3•DMS
(85%)
Diastereoselection > 95 : 5 (anti)
9-BBN
(60%)
Diastereoselection 92 : 8 (syn)
Nakata, Tatsuta & Co-workers, Bull. Chem. Soc. Jpn., 1992, 65, 2974.
Diastereoselective Hydroborations
BH3•THF
BH3•THF
Diastereoselection 92 : 8 (anti)
R = H Diastereoselection 6.8 : 1 (anti)Diastereoselection 6.6 : 1 (anti)R = OBn
K. MoriTetrahedron 1979, 32, 1979.
Oikawa & Co-workersTetrahedron Lett., 1983, 19, 1987.
■ Anti–selective hydroborations with borane
A 2:1 mixture of the lactol:lactone was obtained. This mixture wasoxidized to the keto-lactone in 73% overall yield from the olefin.
Me
OH
MeH
O
Me
Me
OMe
Me
OMe
Me
XP O OH
OH
OH
OBn
OH
Me OBn
OH
Me
O
Me
OH
XP
Me
OMe
Me
OMeMe
O
HMe
OH
Me
Me
OH
MeH
O
MeOMe
Me
OMe
Me
XP O
O
Et
OH
Me
O
Me
TBSO
Me Me
TBSO
Me
Me
Et
OHO O OH
Et
Me
O
Me
TBSO
Me
OH
OH
Me OBn
OH
Me
OH
OH
Me
OH
OBnMe
OBn
OH
OBn
MeMe
OH
OBnMe
OBn
OBn
OH
Me
OH OH OH
OHOHOH
Me
OH
OBn
OBn
Me OBn
OH
Me Me
OBn
OH
OBn
Me OBn
OH
Me
OH
Me
O
O
OO
MeMe
Me
Me O
BnO R
MeMe
OO
Me
RBnO
OH
OMe
Me
O
O
OH
09-Hydroboration-2 3/19/02 2:02 PM
RhLn
Rh cat
CB
Evans & Fu JOC 1990, 55, 2280 and Evans, Fu, Anderson JACS 1992, 114, 6679.
■ Olefin↔catalyst complexation is the stereochemistry-determining step
■ Olefin binding to metal is irreversible for 1,1-disubstituted allylic alcohol derivatives
Stereochemical Model
RhLn
The Catalyzed Hydroboration
■ Complexation involves back-donation from a filled metal d orbital→π*C=C
■ The EWG (alkoxy substituent) is aligned perpendicular to the olefin (π→σ*C—O)
■ This stereoelectronic interaction lowers the energy of π*
■ The small group is placed "inside", the most sterically congested site
CB
Rh cat
syn anti
antisyn
9-BBN
El+
9-BBN
El+
The uncatalyzed variant:Complementary diastereoselectivity for the catalyzed and
uncatalyzed reactions is observed for a wide range of substrates.
Anti Syn
9-BBN
9-BBN
9-BBN
75
72
67
Si(t-Bu)Me2
3 : 9795 : 5
95 : 5
96 : 4
R Conditions Anti : Syn
H50 : 50
15 : 85
68
65
77
Yield (%)
THF
20 °C
The Catalyzed vs Uncatalyzed Hydroboration Reactions
Rh(PPh3)3Cl / CB
Rh(PPh3)3Cl / CB
Rh(PPh3)3Cl / CBSi(t-Bu)Ph2
Evans, Fu, & Hoveyda JACS 1988, 110, 6917 and JACS 1992, 114, 6671.
K. Burgess & Co-workers, J. Org. Chem. 1991, 56, 1020-1027
i-Pr
Me
OR OR
Me
i-Pr i-Pr
R
HR'O
C MeCH
HR
Me
OR'
OR'
Me
R
Me
OR
OH
CH
HCMe
OH
HR'O
R
R
Me
OR'
OHOH
OH OH
OR'
Me
R
R'O
H R
CMe CH
H
R
Me
OR'
OR'
Me
RCH
HC Me
H R
OR'
10-Cat Hydroboration 3/19/02 2:02 PM
E. Vedejs & C. McClure JACS, 1986, 108, 1094.
synanti
synanti
Vedejs Model
OsO4
X = SR, SO2R, SiR3X = OTBS, OAC
OsO4
Kishi Model
OsO4
OsO4
34 : 6622 : 7833 : 6761 : 3962 : 38
selectivity
PhMe2SiPhSO2PhSTBSOAcO
X
(E) Olefins
(z) Olefins
(E) Olefins
(z) Olefins
■ Vedejs argues that hyperconjugative effects are not importantbecause both EDG and EWG provide the same sense of induction
■ Addition occurs anti to the allylic heteroatom functionality
X
PhMe2SiPhSO2PhSTBSOAcO
selectivity
78 : 2280 : 2083 : 1762 : 3870 : 30
OsO4
Diastereoselective Osmylations
James Barrow, Evans Group Seminar, "Osmium Mediated Dihydroxylation:Mechanism and Application" April 21, 1993.
Kishi & Co-workersTetrahedron Lett., 1983, 24, 3943 and Tetrahedron, 1984, 40, 2247.
Acetates give lower selectivity
■ Allylic oxygen protecting group: H, Bn, SiR3, acetonides→all work well
Works for both (Z) and (E) allylic ethers (alchols)OsO4 attacks anti to the allylic oxygen substituentArrange olefin in the stable ground state conformer
■ Kishi's Empirical Model:
OsO4
OsO4
OsO4
X
MeOBn
selectivity
60 : 4081 : 19
50 : 5086 : 14
selectivity
MeOBn
X
Diastereoselective Osmylations
OsO4
Me
OH
Me
X
OH
X Me
H
C HCH
BnO
OH
XR
OH
OH
BnO
BnO
CMe
HC
OH
RX
OH
H
Me
BnO
OH
XX
H
Me
OH
Me
Me
X
OH
OH
OH
Me
OH
Me
C(Me)H
(H)MeC H
HCH2OBn
OBn
X
Me
Me
Me
OH
Me
H
XX
OHMe
C HCMe
H
X
OH
Me
CMe
HCH
MeX
H
Me
11-Osmylations 3/19/02 2:02 PM
Houk, JACS, 1986, 108, 2754.
■ Oxygen avoids "outside" position to avoid repulsiveelectrostatic interactions with the incoming OsO4
anti
syn
OsO4
OsO4
"inside alkoxy"
Houk Model: Staggered transition states
Vedejs model breaks downor iPr, Ph > Me2PhSi
synanti
syn
OsO4
Fleming, JCS Perkin Trans I, 1992, 3303-3308.
RatioR
34 : 66 67 : 33 92 : 08
MeiPrPH
OsO4
Diastereoselective Osmylations
PhMe2Si
MeR R Me R Me
PhMe2Si PhMe2Si
OH
OH
OH
OH
H
PhMe2SiR
CH CH
Me
CMe
HCH
HXO
R
R
HXO
C HCH
Me
OH
OH
OH
OH
XO
XO
MeR
MeR
12-Osmylation 3/19/02 2:02 PM
top related