Embed Size (px)
Citation preview
Strain Release Lewis Acidity: Recent AdvancesIn Asymmetric Synthesis
Aparajita BanerjeeOrganic Seminar
December 13, 2006
M
Nu
. .
D
C
A
B
M
A
B
Nu
C
D
Outline Introduction - Basic Principle
Application In Carbon—Carbon bond forming Reactions - 4 Membered Silacycle - Aldol and Asymmetric Aldol Reaction - Addition To α,β-Unsaturated Carbonyl - Allylation Reaction - 5 Membered Silacycle - Asymmetric Allylation/Crotylation Reaction - Enantioselective Friedel-Crafts Alkylation Reaction - Enantioselective [3 + 2] Cycloaddition Reaction - Asymmetric Diels Alder Reaction - Tandem Reaction
Application In Natural Product Synthesis
Strain Release Chemistry With Al
Conclusion
Outline Introduction - Basic Principle
Application In Carbon—Carbon bond forming Reactions - 4 Membered Silacycle - Aldol and Asymmetric Aldol Reaction - Addition To α,β-Unsaturated Carbonyl - Allylation Reaction - 5 Membered Silacycle - Asymmetric Allylation/Crotylation Reaction - Enantioselective Friedel-Crafts Alkylation Reaction - Enantioselective [3 + 2] Cycloaddition Reaction - Asymmetric Diels Alder Reaction - Tandem Reaction
Application In Natural Product Synthesis
Strain Release Chemistry With Al
Conclusion
Basic Principle
Tetracoordinated Silane:
Tetracoordinated Silacycle (4 or 5 membered):
Common Lewis Acids: Electron Deficient Compounds: BF3, AlCl3
Denmark, S. E.; Jacobs, R. T.; Dai-Ho, G.; Wilson, S. Organometallics 1990, 9, 3015Zhang, X.; Houk, K. N.; Leighton, J. L. Angew. Chem. Int. Ed. 2005, 44 , 9938
Si
Actual angle ~ 90o
Expected Angle 109.5o
Highly strained
High Lewis acidity
Nu. .
Actual angle ~ 90o
Expected Angle 90o
Trigonal bipyramidal
Strain released
C
D
B
A
Si
B
A
Nu
D
C
Nu
. .
Low Lewis acidity
Si
C
D
B
A
Nu
SiA
B
C
D
90o109.5o
Example of Strain Release Lewis Acidity Aldol Reaction
Denmark, S. E.; Griedel, B. D.; Coe, D. M. J. Org. Chem. 1993, 58, 988Matsumoto. K.; Oshima, K.; Utimoto, K. J. Org. Chem. 1994, 59, 7152
Acyclic Analogue
Cyclic Analogue
Allylation of Aldehyde
Dual Activation of the silane and aldehyde
Acyclic Analogue
Cyclic Analogue
O
SiH
Ph
Ph
H3CO
OSi
t-Bu
H3C CH3
+
H
O
Ph
C6D6 / 1M
20 oC
120 h
No Reaction
CH3
+H
O
Ph
CDCl3 / 1M
20 oC
2.2 h94%
H3CO
OSi
t-Bu
CH3
E:Z (95:5)
H3C
O
Ph
OH
CH3
H3C
O
Ph
CH3
OH
+ 95:5
PhSi
H3C CH3 +H
O
Ph
160 oC
24 h
No Reaction
PhSi
+
H
O
Ph
130 oC
12 hPh
OSi
Phaq. HCl
MeOH
Ph
OH
85%
SiMe
O
O
MeO CH3
CH3
H
Ph
Historical Background
Perozzi, E. F.; Michalak, R. S.; Figuly, G. D.; Stevenson, W. H. III, Bess, D. B.; Ross, M. R.; Martin, J. C. J. Org. Chem. 1981, 46, 1049Stevenson III, W. H.; Wilson, S.; Martin, J.C.; Farnham, W. B. J. Am. Chem. Soc. 1985, 107, 6340
Si
O
O
Si
4 coordinated
Distorted Tetrahedral
Si
5 coordinatedTrigonal Bipyramidal
SiO
O
Endocyclic C-Si-O ~ 94.4o Endocyclic C-Si-O ~ 85.3o
SiO
O
CF3CF3
CF3
CF3
O
Si
O
F3C CF3
F3CCF3
LiPhLi
A B
Hypervalency of Silicon
∆E > 200 kCal/mol
10 electrons4 orbitals ?
Hypervalent BondingConcept of 3c-4e bond
Alekseev, N. V.; Heller, G.; Niedenzu, K.; Tandura, S. N.; Trofimenko, S.; Vorkonkov, M. G. Top. Curr. Chem. 1986, 131, 99
Involved in the formation of 5 bonds
Si
Possibility 1
3S
3p
3d
sp2
dp
hybridize
sp3d
Energyp
d
sp2
sp2p
Possibility 2
Hypervalent Bonding: Concept of 3c-4e bond
Electron Distribution:
3 sp2 hybrid orbitals 6 electrons 1 X 3c-4e bond 4 electrons Total 10 electrons
Mixing of Bonding and Nonbonding MOsHypervalent Bond(p orbitals)
Consequences of 3c-4e bond
Shift of electron density from central atom to ligand
Electron withdrawing ligands preferred
Axial bonds larger than equatorial bond length
Alekseev, N. V.; Heller, G.; Niedenzu, K.; Tandura, S. N.; Trofimenko, S.; Vorkonkov, M. G. Top. Curr. Chem. 1986, 131, 99
Si
L
L
Bonding
Nonbonding
Antibonding
E
Si LL
(HOMO)
Proof of 3c-4e Bond from Crystal Structure
DistortedTetrahedral
Trigonal Bipyramidal
Bond Length: Si–O 1.654 Å Si–C 1.835 ÅBond Angle:Endocyclic C-Si-O ~ 94.4o
(Ideal 109.5o)
Expected
Highly strained
Bond Length: Si–O 1.818 Å Si–C 1.922 ÅBond Angle: Endocyclic C-Si-O ~ 85.3o
(Ideal 90o)Release of strain
Longer than expected
Average increase in Bond Length: Si–O 0.162 Å Si–C 0.085 Å
Greater increase in apical bond length 3c-4e bond
Stevenson III, W. H.; Wilson, S.; Martin, J.C.; Farnham, W. B. J. Am. Chem. Soc. 1985, 107, 6340
Si
O
CF3
OF3CCF3
CF3
O
Si
O
Ph
F3C CF3
CF3F3C
Me4N
Si
O
O
SiO
O
‘Strain Release Lewis Acidity’
Denmark, S. E.; Jacobs, R. T.; Dai-Ho, G.; Wilson, S. Organometallics 1990, 9, 3015
If ∠A-X-B less than 94.40
Further distortion in tetrahedral geometry more strained greater Lewis acidity
A
X
B C
DX = Si, ∠A-X-B = 94.40
?
by Germanium
Bond Length: Ge–O 1.989 Å Ge–C 1.951 Å
Bond Angle:Endocyclic C-Si-O ~ 83.5o
(Ideal 90o)
GeO
O
F3C CF3
F3CCF3
Bond Length: Ge–O 1.786 Å Ge–C 1.898 ÅBond Angle: Endocyclic C-Ge-O ~ 91.5o
(Ideal 109.5o)
Expected
More strainedthan Si analogue
Longer than expected
Release of strain
Expected:Ge analogue much more Lewis acidic than Si analogue
Ge
O
O
CF3F3C
CF3F3C
Et4N
Ge
Ge
O
O
O
O
DistortedTetrahedral
Trigonal Bipyramidal
Average increase in Bond Length: Gei–O 0.203 Å Ge–C 0.053 Å
Enhanced Lewis Acidity by Germanium Analogue
Denmark, S. E.; Jacobs, R. T.; Dai-Ho, G.; Wilson, S. Organometallics 1990, 9, 3015
Ge analogue much more Lewis acidic than Si analogue : Proof
Intramolecular Ene Reaction:
Intramolecular [4+2] Cycloaddition Reaction:
No Reaction with Si Analogue
No Reaction with Si Analogue
GeO
O
F3C CF3
F3CCF3
1
CHO
CH3H3C
H3C CH3
1
CH2Cl2/ 20 oC OH
H3C CH3
H3C
+
H3C CH3
H3C
OH
trans cis
CH3
H
O
SCH3
1
CH2Cl2 / 20 oC
63%
O
H
H
CH3
SCH3
E-isomertrans-isomer
Si More explored because of its practical applicability
Different Silacycles
4-Membered silacycle
Ring spans along axial-equatorial
Ring spans along axial-equatorial
X, Y O, OX, Y O, N X, Y N, N
Si Si
Nu
4-coordinated 5-coordinated
Nu
Si
X
YSi
X
Y
Nu
4-coordinated 5-coordinated
Nu
Denmark, S. E.; Griedel, B. D.; Coe, D. M. J. Org. Chem. 1993, 58, 988Kinnaird, J. W. A.; Ng, P. Y.; Kubota, K.; Wang, X.; Leighton, J. L. J. Am. Chem. Soc. 2002, 124, 7920
5-Membered silacycle
Comparison: Four vs Five Membered Ring
DFT Calculation performed with Gaussian03 B3LYP-6-31G++(d,p)
4-membered Silacycle
5-membered Silacycle
4-coordinated 5-coordinated
ExpectedAngle 90°
Outline Introduction - Basic Principle
Application In Carbon—Carbon bond forming Reactions - 4 Membered Silacycle - Aldol and Asymmetric Aldol Reaction - Addition To α,β-Unsaturated Carbonyl - Allylation Reaction - 5 Membered Silacycle - Asymmetric Allylation/Crotylation Reaction - Enantioselective Friedel-Crafts Alkylation Reaction - Enantioselective [3 + 2] Cycloaddition Reaction - Asymmetric Diels Alder Reaction - Tandem Reaction
Application In Natural Product Synthesis
Strain Release Chemistry With Al
Conclusion
Si Directed Aldol Reaction
Myers, A. G.; Widdowson, K. L. J. Am. Chem. Soc. 1990, 112, 9672
Asymmetric Version:
Without apparent Catalyst Pericyclic transition state
OSi(CH2CH3)2
NH3C
CH3
CH3
H
O
H
OSi(CH2CH3)2O
CH3
H3C
CH3
OSi(CH2CH3)2O
CH3
H3C
CH3
+ +CH2Cl2
-30 oC
1 anti syn
1.8:1
N
O
SiO
CH3
CH3
H
CH3
H+
H
O
hexane
23 oC, 10 hN
O OO Si
H3CCH3
CH3
H
N
O OO Si
H3CCH3
CH3
H
+
anti-isomer syn-isomer39:1
yield: 77% (for anti-isomer)
2
Mechanism:
Myers, A. G.; Kephart, S. E.; Chen, H. J. Am. Chem. Soc. 1992, 114, 7922
Path A Path B
Si Directed Aldol Reaction
Si
R
OO
N
H
CH3
R
Si
R
O
O H
R = CH3
pseudo rotation
SiO
N
O
R
OH
H
CH3
RSi
O
N
O
O
H
CH3H
R
R
NH
H3C
OR
Si
R
OO
N
H
CH3
R
Si
R
H
CH3
R
O
N
O
O H
R = CH3
pseudo rotation
SiO
N
O
R
OH
H
CH3
R
SiO
N
O
O
H
CH3H
RR
Si Directed Aldol ReactionMechanism:
Path A Path B
10 fold rate acceleration for silacyclopentane 2X106 fold rate acceleration for silacyclobutane Path A: Operative
Si
R
OO
N
H
CH3
R
Si
R
H
CH3
O
N
O
O H
R = (CH2)3 R= (CH2)4
pseudo rotation
SiO
N
O
R
OH
H
CH3
R
SiO
N
O
O
H
CH3H
RR
R Si
R
OO
N
H
CH3
R
Si
R
O
O H
R = (CH2)3
R = (CH2)4
pseudo rotation
SiO
N
O
R
OH
H
CH3
RSi
O
N
O
O
H
CH3H
R
R
NH
H3C
OR
ExpectedAngle: 90o Expected
Angle: 90o
Si Directed Aldol Reaction
Rate enhancement with a small ring:
Acyclic Analogue
Cyclic Analogue
Myers, A. G.; Kephart, S. E.; Chen, H. J. Am. Chem. Soc. 1992, 114, 7922
OSi
Ph
H3C CH3
+
H
O
Ph
C6D6
150 oC
200 hNo Reaction
OSi
Ph
+
H
O
Ph 34 h84%
O O
Ph
SiPh
syn:anti 7:1
C6D6
100 oC
Synthesis of Cyclic Silylenol Derivative
Laane, J.; J. Am. Chem. Soc 1967, 89, 1144Denmark, S. E.; Griedel, B. D.; Coe, D. M. Schnute, M. E. J. Am. Chem. Soc. 1994, 116, 7026
H2C CHCH2Cl + HSiCl3
H2PtCl6
heatCl3SiCH2CH2CH2Cl
Si
Cl Cl
Mg, THF
t-BuLi87%
Si
Cl t-Bu
O
H3CO
LDA, THF72%
Si
O t-Bu
H3CO CH3
Si
Cl Cl
Mg
THF66%
Aldol Reaction of Silyl-enol derivative of Ester
Denmark, S. E.; Griedel, B. D.; Coe, D. M. J. Org. Chem. 1993, 58, 988Denmark, S. E.; Griedel, B. D.; Coe, D. M. Schnute, M. E. J. Am. Chem. Soc. 1994, 116, 7026
Cyclic Analogue
Acyclic Analogue
t1/2
entry R1 R2 R3 R4 (min)
1
2
3
4 t-butyl
t-butoxy
t-butyl
t-butyl
5
33
2100
-
CH3
CH3
CH3
CH3 CH3
CH3
CH3
CH3CH3
CH3
CH3
CH3
O
MeO
Sit-Bu
CH3H3C
CH3
+
Ph H
O 1M C6D6
120 h
No Reaction
Si O
R2
R3
R4R1O
PhCHO
C6D6, 1M
20 oC
O O
R1O
R3 R4Ph
SiR2
O
Me
MeSi
MeO
Me
+
O
H
SiMe
O
O
MeO CH3
CH3
H
Ph
O
MeO
SiOCHPh
H3C CH3
CH3
O
Ph
H
O O
MeO
H3C CH3
SiMe
Path A
Intramolecular silicon group
transfer
O O
MeOH3C CH3
Si
H3C
PhCHOPath B
Intermolecular silicongroup transfer
Open TS
Closed TS
Crossover Experiment Path A
Aldol Reaction: Asymmetric Version
Proposed Asymmetric Variant of Aldol Reaction
Denmark, S. E.; Griedel, B. D. J. Org. Chem. 1994, 59, 5136
O
Me
Si
X
R*ORCHO
Si
O
O
X Me
H
R1
OR*
O OSi
Me
X R1
O OH
OR*
X
Me
R*OH +
HF, THF
SiCl Cl
R1
With Chiral Enoxysilacyclobutane derived from ester
Denmark, S. E.; Griedel, B. D. J. Org. Chem. 1994, 59, 5136
Important Observations:
- Unaaceptably low yield due to large component C-silyl esters and (Z)-ketene acetal isomers
X
O
CH3
Si
Y
Si
CH3X
OY
a b
1a, b: X = OCH3, Y = (-)-8-phenylmenthol2a, b: X = OCH3, Y = (-)-trans-2-cumylcyclohexanol
oxygen silylated carbon-silylated
Aldol Reaction: Asymmetric Version
entry ketene temp, °C syni/anti ee (%) acetal
1 1 -60 >99/1 95
2 2 -60 >99/1 97
CH3O
OSi
R*O
CH3
+ PhCHO1) 0.5M, toluene
2) 1 h, HF/THF/H2O
R*OH
60/40 Oxygen vs Carbon-silyl
80/20 E/Z
O
PhH3CO
OH
CH3
syn-isomer
With chiral Enoxysilacyclobutane derived from thio ester
Denmark, S. E.; Griedel, B. D. J. Org. Chem. 1994, 59, 5136
For thio ester enolate: b < 2%
Synthetic Utility:
X
O
CH3
Si
Y
Si
CH3X
OY
ab
1a, b: X = SCH3, Y = (+)-trans-2-cumylcyclohexanol
Aldol Reaction: Asymmetric Version
OSi
O
CH3
H3CH3C
CH3SPh
1) PhCHO toluene, -35 °C, 2M, 7d
2) HF / THF / H2O
O OH
CH3S Aryl
CH3
(1S, 2S)94% ee
60%
O
CH3S Ph
CH3
OHHg(OAc)2, 5 eqNa2HPO4, 5 eq
MeOH, 12 h90%
O
CH3O Ph
CH3
OH
Outline Introduction - Basic Principle
Application In Carbon—Carbon bond forming Reactions - 4 Membered Silacycle - Aldol and Asymmetric Aldol Reaction - Addition To α,β-Unsaturated Carbonyl - Allylation Reaction - 5 Membered Silacycle - Asymmetric Allylation/Crotylation Reaction - Enantioselective Friedel-Crafts Alkylation Reaction - Enantioselective [3 + 2] Cycloaddition Reaction - Asymmetric Diels Alder Reaction - Tandem Reaction
Application In Natural Product Synthesis
Strain Release Chemistry With Al
Conclusion
1,2 vs 1,4-addition:
Why the observed regiochemistry?
Denmark, S. E.; Griedel, B. D.; Coe, D. M. Schnute, M. E. J. Am. Chem. Soc. 1994, 116, 7026
OSi
CH3OH
CH3
t-Bu+
O
H 20 °C
O
CH3O
H CH3
Sit-Bu
H +O
H
O
H3CO
SiR
1,2-addition 1,4-addition
C6D6
t1/2 = 8 min
84%
100:0
SiR1
O
O
MeO CH3
CH3R2
SiR1
O
MeO CH3
CH3
6 Membered TS
Eneregetically Accessible8 Membered TS
O
R2
Addition To α,β-Unsaturated Carbonyl
Outline Introduction - Basic Principle
Application In Carbon—Carbon bond forming Reactions - 4 Membered Silacycle - Aldol and Asymmetric Aldol Reaction - Addition To α,β-Unsaturated Carbonyl - Allylation Reaction - 5 Membered Silacycle - Asymmetric Allylation/Crotylation Reaction - Enantioselective Friedel-Crafts Alkylation Reaction - Enantioselective [3 + 2] Cycloaddition Reaction - Asymmetric Diels Alder Reaction - Tandem Reaction
Application In Natural Product Synthesis
Strain Release Chemistry With Al
Conclusion
Allylation Reaction: With Four Membered Silacycle
Acyclic Analogue
Cyclic Analogue
Allyl-alkoxy silacyclobutane more reactive than Allyl-phenyl silacyclobutane
Matsumoto. K.; Oshima, K.; Utimoto, K. J. Org. Chem. 1994, 59, 7152
PhSi
H3C CH3+
H
O
Ph
160 oC
24 hNo Reaction
PhSi
+H
O
Ph
130 oC
12 hPh
OSi
Phaq. HCl
MeOH Ph
OH
85%
+H
O
Ph
1. 100 oC
12 h
Ph
OHSi
O 2. aq. HCl83%
Allyl-Phenyl silacyclobutane with aldehydes:
Matsumoto. K.; Oshima, K.; Utimoto, K. J. Org. Chem. 1994, 59, 7152
R1 R2 Yield anti/syn
H
n-Pr
n-Pr
H
68
66
95/5
5/95
E
Z
Allylation Reaction: With Four Membered Silacycle
Si
Ph Cl -78 °C - rt96%
Si
Ph
MgCl+ THF
Synthesis of Allylsilyl Reagent:
O
SiH
H
n-Pr
R
PhO
SiH
n-Pr
H
R
Ph
anti isomer syn-isomer
E-isomer Z-isomer
PhSi +
H
O
Ph
1. 130 oC, 24 h
2. aq. HCl Ph
OH
R1
R2
R1 R2
Ph
OH
R2 R1
+
anti syn
Outline Introduction - Basic Principle Application In Carbon—Carbon bond forming Reactions - 4 Membered Silacycle - Aldol and Asymmetric Aldol Reaction - Addition To α,β-Unsaturated Carbonyl - Allylation Reaction
- 5 Membered Silacycle - Asymmetric Allylation/Crotylation Reaction - Enantioselective Friedel-Crafts Alkylation Reaction - Enantioselective [3 + 2] Cycloaddition Reaction - Asymmetric Diels Alder Reaction - Tandem Reaction
Application In Natural Product Synthesis Strain Release Chemistry With Al
Conclusion
Introduction of the Asymmetry: Choice of Chiral auxiliary :
Si
O
O Cl
H3C
H3C
H3C
H3C
Ring induces: - reactivity - chirality
Chiral 1,2-amino alcohols
OH
NH
Me
Me
Ph
Kinnaird, J. W. A.; Ng, P. Y.; Kubota, K.; Wang, X.; Leighton, J. L. J. Am. Chem. Soc. 2002, 124, 7920
Chiral 1,2-diamines
NHBn
NHBn
Inactive Catalyst
Asymmetric Allylation Reaction With Five Membered Silacycle
O
Si
O
ClMe
Me
Me
Me
O
Si
O
MeMe
MeMe
ClN
Si
N
Cl
Me
Me
acyclic six-membered
A B CO
Si
OMe
Me
Me
Me
Cl
+
O
HPh
Toluene
23 °C
52%
OH
Ph
1
Asymmetric Allylation Reaction With Five Membered Silacycle
Synthesis of Chiral Silane Reagent:
From Chiral 1,2-amino alcohols
From Chiral 1,2-diamines
Kinnaird, J. W. A.; Ng, P. Y.; Kubota, K.; Wang, X.; Leighton, J. L. J. Am. Chem. Soc. 2002, 124, 7920Kubota, K.; Leighton, J. L. Angew. Chem. Int. Ed. 2003, 42 , 946
NH
NH
p-BrC6H4
p-BrC6H4
(R,R)
CH2Cl2
88%
Cl3Si+
DBU
NSi
N
Cl
p-BrC6H4
p-BrC6H4
(R,R)
2
(S,S)
OH
NH
MeMe
Ph
NSi
O
Cl
CH3
H3C
Ph
CH2Cl2
88%
Cl3Si+
Et3N
2:1 dr
1
Kinnaird, J. W. A.; Ng, P. Y.; Kubota, K.; Wang, X.; Leighton, J. L. J. Am. Chem. Soc. 2002, 124, 7920Kubota, K.; Leighton, J. L. Angew. Chem. Int. Ed. 2003, 42 , 946
Asymmetric Allylation Reaction With Five Membered Silacycle
With aldehyde:
2
N
Si
O
Cl
CH3
H3C
Ph O
Ht-Bu
TolueneOH
t-Bu+
96% ee
- 10 oC, 2 h (S)
(S,S)
80%
1
N
Si
N
Cl
p-BrC6H4
p-BrC6H4
+
O
HPh- 10 °C, 20 h
OH
PhCH2Cl2
(R,R)
S-isomer
98% ee69%
(Z)-crotylsilane: Syn-Selective
Hackman, B. M.; Lombardi, P. J.; Leighton, J. L. Org. Lett. 2003, 42 , 946
With Aldehyde
(E)-crotylsilane: Anti-Selective
Asymmetric Crotylation Reaction With Five Membered Silacycle
Entry R Yield(%) ee(%)
1
2
3
4
5
PhCH2CH2
p-CF3C6H4
83
82
67
61
97
97
96
95
96
BnOCH2
6 67 95
Cy
Ph
PhHC CH(E)
67
81
83
54
60
98
97
99
93
96
52 94
68
(trans)-crotylsilane
Yield(%) ee(%
(cis)-crotylsilane
+
O
HR 0 °C, 20 h
OH
R
CH2Cl2
CH3
NSi
N
p-BrC6H4
p-BrC6H4
(R,R)-2
Cl
CH3
1.1 equiv
+
O
HR 0 °C, 20 h
OH
R
CH2Cl2
(R,R)-3
NSi
N
Cl
p-BrC6H4
p-BrC6H4
CH3
(1.1) equiv
CH3
Berger, R.; Rabbat, P. M. A.; Leighton, J. L. J. Am. Chem. Soc. 2003, 125, 9596
Aldehyde derived Acylhydrazone
N
Si
N
NR2
R1H
Ph
H
NOCl
Asymmetric Allylation/Crotylation Reaction
NSi
O
Cl
CH3
H3C
Ph
N
HPhPh
+NH
O R
CH2Cl2
0 or 10 oC
HNNH
O R
a) R = t-Bub) R = Me
a) 70%, 40% eeb) 86%, 88% ee
N
Si
N
OR2
R1H
Ph
H
Ph
NOCl
N
Si
O
Cl
CH3
H3C
Ph
R2
R1
N
HPh
NHBz
Ph
HNNHBz
R2 R1
+
CH2Cl2
10 oC
a. R1 = CH3, R = H
b. R1 = H, R = CH3
a. 81%; 96:4 dr; 95% eeb. 89%; 95:5 dr; 97% ee
N
Si
O
Cl
CH3
H3C
Ph
N
HPh Ph
HN+
N N
CH2Cl2
31%, 50% ee
Crotylation:
Allylation:O
N
Si
Cl
CH3
N
HPh
NHAc
+CH2Cl2
0 oC, 16h
44%
HNNHAc
Ph
Proposed mechanism:
Berger, R.; Duff, K.; Leighton, J. L. J. Am. Chem. Soc. 2004, 126, 5686
Ketone derived Benzoylhydrazone
Asymmetric Allylation Reaction With Five Membered Silacycle
N
Si
N
O
Ph
H3C
H
Ph
NO
ClMe
N
Si
N
O
Ph
H3CPh
NO HCl
Me
N
Si
N
O
Ph
H3CPh
HClNO Me
N
HPh
NHBz
NSi
O
Cl
CH3
H3C
Ph
(S,S)
+
(1.5 equiv)
N
CH3Ph
NHBz
R1+CHCl3
40 oC, 24 hN
Si
O
Cl
CH3
H3C
Ph NHNHBzR2
86%, 90% ee
Berger, R.; Duff, K.; Leighton, J. L. J. Am. Chem. Soc. 2004, 126, 5686
Ketone derived Benzoylhydrazone
Asymmetric Allylation Reaction With Five Membered Silacycle
OSi
NN
Ph
O
N HPh
CH3
CH3 Cl
+
-
Ph
H
Ph
NSi
O
OMeCH3
H3C
Ph
(S,S)
+N
Me
NMe
Ph
PhO
N
Me
NH
Ph
PhO
NRNSi
O
Cl
CH3
H3C
Ph
+
N
Si
O
Cl
Ph
CH3
H3C
Ph
+N
H
NH
Ph
PhO
White Powder
1
Rabbat, P. M. A.; Valdez, S. C.; Leighton, J. L. Org. Lett. 2006, ASAP
?
No reaction
With Aldimine
H3CO
H2N
CH3
NSi
O
Cl
CH3
H3C
Ph
(S,S)-1
Asymmetric Allylation Reaction With Five Membered Silacycle
R1
OSi
N
O
N HPh
CH3
CH3 Cl
+
-
R
H
HN
O R3
R2 NH
HO
N
HR
(S,S)-1
N
H
HO
CH3
HN
HO
CH3
Et2O, 23 oC
20 h
85%
(S,S)-1
92% ee
(S,S)-1
NSi
O
Cl
CH3
H3C
Ph
N
R2R1
R1
+NH
O R3
OSi
NN
R3
O
N HPh
CH3
CH3 Cl
+
-
R2
R1
HN
O R3
R2 NH
Rabbat, P. M. A.; Valdez, S. C.; Leighton, J. L. Org. Lett. 2006, ASAP
NOH
CH3
Asymmetric Allylation Reaction With Five Membered Silacycle
Phenol Activating/directing group attached to imine nitrogen part of the substrate ?
Advantage
Possibility of success with Ketimines Flexibility in the choice of N-substituent of the imine
With Ketimine
RCH3
N
HO
Ketimine Not Possible
Limitation: Only applicable to Ketimine containing Phenolic auxiliiary
N
CH3
OH(S,S)-1Toluene
reflux, 6 h90%
NHOH
96% ee
5 mol % Grubbs II cat.
40 oC, 14 h
82%
NH
OH
96% ee
Burns, N. Z.; Hackman, B. M.; Ng, P. Y.; Powelson, I. A.; Leighton, J. L. Angew. Chem. Int. Ed. 2006, 45, 3811 ,
Sterically Hindered Ketone
Asymmetric Allylation Reaction With Five Membered Silacycle
(R) Enantiomer (major)(S) Enantiomer
Proposed mechanism:
NSi
N
Cl
p-BrC6H4
p-BrC6H4
+
HO OHO HO
H3CH3C
(R,R) 94% ee
CH2Cl2
23 °C, 48 h75%
O
Si
R
N
N
H
H
Ar
Ar
+ HCl-
O HO RH
O
Si
N
N
H
H
Ar
+ H
O
Ar
Cl -
Electronic Repulsion
StericRepulsion
OH
HO R
kA kB
AB
O
kB >> kA
R
Outline Introduction - Basic Principle
Application In Carbon—Carbon bond forming Reactions - 4 Membered Silacycle - Aldol and Asymmetric Aldol Reaction - Addition To α,β-Unsaturated Carbonyl - Allylation Reaction - 5 Membered Silacycle - Asymmetric Allylation/Crotylation Reaction - Enantioselective Friedel-Crafts Alkylation Reaction - Enantioselective [3 + 2] Cycloaddition Reaction - Asymmetric Diels Alder Reaction - Tandem Reaction
Application In Natural Product Synthesis
Strain Release Chemistry With Al
Conclusion
Different Approach in Carbon-Carbon Bond Forming Reaction
N
Si
O
Me
Ph
Me
Cl
Nucleophile present in the silane moiety
NSi
O
Me
Ph
Me
Cl
Ph+ External Nucleophile
?
Yes
Enantioselective Friedel-Crafts Alkylation
Enantioselective [3 + 2] Acylhydrazone-Enol Ether Cycloaddition
N
Si
O
Cl
Ph
CH3
H3C
Ph
+
N
R2R2
NHCORArH
? R1 Ar
R2 NHNHCOR
N
Si
O
Cl
Ph
CH3
H3C
Ph
+
N
HR2
NHCOR
?
EDGHN N
R1 EDG
O
R
Enantioselective Friedel-Crafts Alkylation
Shirakawa, S.; Berger, R.; Leighton, J. L. J. Am. Chem. Soc. 2005, 127, 2858
OSi
N
N
Ph
O
NHPh
CH3
CH3 Cl
+
-
Ph
H
Ph
ArH
ArH
Bulky Phenyl Group
X
Plausible Mechanism :
+N
Hi-PrO2C
NHBz
ArH
(1.5 equiv)(S,S)-1
Toluene, -20 oC, 20 h Ari-PrO2C
NHNHBz
OSi
NPh
O
N HPh
CH3
CH3 ClH
+
-
Ph
H
Ph
NSi
O
Cl
CH3
H3C
Ph
N
HPh
+NH
O Ph
(S,S)-1(~2:1) dr
Entry ArH Yield(%) ee(%)
1 65 95
NMe2
NH
NO2
N
S
Bn
OMe
2
3
4
74
76
91
88
88
89
Enantioselective [3 + 2] Acylhydrazone-Enol Ether Cycloaddition
Stepwise mechanism
Shirakawa, S.; Lombardi, P. J.; Leighton, J. L. J. Am. Chem. Soc. 2005, 127, 9974
Extension: Access to 1,3-diamines
+ HN N
t-Bu
O
Ph
OtBuN
t-Bu H
NHBz
OtBu(3.0 equiv)
(1.5 equiv)(S,S)-1
Toluene, 23 oC, 24 h
76%>97:3 dr98% ee
HN N
Bz
OtBu
PhN N
Bz
OtBu
PhAc
N N
BzPhPh NH HN
Ac Bz Ac
AcCl, Pyridine
DMAP, CH2Cl2
99%
MeOH, THF
87%
H2C CHCH2SiMe3
TMSOTf
CH2Cl2,-15oC
65%; >20:1 dr
SmI2
NSi
O
Cl
Ph
CH3
H3C
Ph
(S,S)-1(~2:1) dr
+
HN N
Bz
OtBuN
R H
NHBz
OtBu
(3.0 equiv)
(1.5 equiv)(S,S)-1
Toluene, 23 oC, 28 h
70%
Ph
CH3
>10:1 dr;97% ee
(Z)anti
Asymmetric Diels–Alder Cycloaddition
Model for Asymmetric Induction
Kubota, K.; Hamblett, C. L.; Wang, X.; Leighton, J. L. Tetrahedron, 2006, 62, 11397
O
tBu
N
tBu
N
Si
Cl
Ts
A
OtBu
N
tBu
N
Si
Cl
Ts
Inactive Catalyst
B
R1 CHO+
20 mol %A
CH2Cl2, - 78 oC R1
CHO
R2 R2
Entry Enal time(h) Yield(%) ee(%)
1 78 94
2
3
4
87
79
88
90
86
54
Me CHO
Me CHO
Me
CHO
Et CHO
8
48
24
16
CH3
CHOSi N
N
O
H
Ts
Cl
H
H3C
HO
Si N
NH
Ts
Cl
H
O H
H3C
O
(S)
Cooperative H-bonding
Bulky Ph Ring
Outline Introduction - Basic Principle
Application In Carbon—Carbon bond forming Reactions - 4 Membered Silacycle - Aldol and Asymmetric Aldol Reaction - Addition To α,β-Unsaturated Carbonyl - Allylation Reaction - 5 Membered Silacycle - Asymmetric Allylation/Crotylation Reaction - Enantioselective Friedel-Crafts Alkylation Reaction - Enantioselective [3 + 2] Cycloaddition Reaction - Asymmetric Diels Alder Reaction - Tandem Reaction
Application In Natural Product Synthesis
Strain Release Chemistry With Al
Conclusion
Tandem Aldol-Allylation Reaction
Potential Problem in Polyketide Synthesis: Oligomerization
Possible Solution: Termination by allylation
Wang, X.; Meng, Q.; Nation A. J.; Leighton, J. L. J. Am. Chem. Soc. 2002, 124, 10672
O
Si
OMe
Me
Me
Me
O
1
Reaction:
+
OH OH
Ph
O
HPh
1
Toluene
40 °C, 24h
OH
Ph
60%; 11:1 dr 29%
O
HR
+ H3C
OMLn
n
OH OH O
CH3 CH3
HR n-1
OH OH OH
CH3 CH3
R n-1
CH3
O
HR+
H3C
O
LnM
CH3n
Tandem Aldol-Allylation Reaction: Extension
O
Si
O
O
H3C
H3C
H3C
H3CO
Si
O
O
H3C
H3C
H3C
H3C
Three Stereogenic Centres Four Stereogenic Centres
Wang, X.; Meng, Q.; Nation A. J.; Leighton, J. L. J. Am. Chem. Soc. 2002, 124, 10672Wang, X.; Meng, Q.; Nicholas, R. P.; Xu, Y.; Leighton, J. L. J. Am. Chem. Soc. 2005, 127, 12806
O
Si
O
O
H3C
H3C
H3C
H3C
Tertiary Carbinol
O
HCy
Toluene40 °C, 60 hO
SiOMe
Me
Me
MeO
OH OH
Cy
CH3
30%; 2:15 dr
Toluene40 °C, 60 h
OSi
OMe
Me
Me
MeO
H3COH OH
Cy
CH3
71%; 10:1 dr
Cy H
O
O
HCy
Toluene40 °C, 80 h
OSi
OMe
Me
Me
MeO
OH OH
Cy
CH3
81%; 66:5:24:7:4 dr
CH3
H3C
CH3
Toluene
OSi
OMe
Me
Me
MeO
O
HCy+
CH3
CH3 Cy
58%; 14:1 dr
CH3
CH3
reflux, 50 h
HO HO
Aldehyde added Externally
Tandem Silylformylation—Allyl(Crotyl)silylation
Allylation: Silylformylation of Olefins:
Predicted Scheme:
- Important structural motif found in natural product
Chapman, E.; J.; Leighton, J. L. J. Am. Chem. Soc. 1997, 119, 12416Zacuto, M. J.; Leighton, J. L. J. Am. Chem. Soc. 2000, 122, 8587
SiO
R H
OPh Ph
O HSi
R
Ph Ph
Rh(acac)(CO)2
CO, Benzene, 60 oCN
Si
O
Me
Ph
Me
Cl
+
Ph H
O Benzene
Ph
OH
O HSi
R
SiO
R H
OOH OH OH
R
O Si O
R
Tamao
Oxidation
O Si O
R *H
OSiO
R
O
R
SiH
Tandem Silylformylation—allylsilylation
Zacuto, M. J.; Leighton, J. L. J. Am. Chem. Soc. 2000, 122, 8587O’Malley, S. J.; Leighton, J. L. Angew. Chem. Int. Ed. 2001, 40, 2915
Alkene Substrate
Alkyne Substrate
O HSi
i. 3 mol % Rh(acac)(CO)2,
1000 psi CO, Benzene, 60 oC
ii. H2O2, NaHCO3, THF/MeOH, heat
OH OH OH
i-Pr
i-Pr
59%, 77:23 ds
OSi
H
CH3
H3C
OAc OAc
CH3
H3C
1.i. Rh(acac)(CO)2,
CO, Benzene, 60 oC
ii. n-Bu4NF, THF, heat
2. Ac2O, Pyridine 83%; 8:1 dr
Schmidt, D. R.; O’Malley, S. J.; Leighton, J. L. J. Am. Chem. Soc. 2003, 125, 1190
With Alkyne Substrate: Access to Both syn and anti 1,5-diol
BDPP: (2,4)-bis(diphenylphosphino)pentane
Entry R1 R2 Ligand ds Yield
1
2
3
4
75
89
83
8212:88
90:10
20:80
80:20(R,R)-BDPP
(S,S)-BDPP
(R,R)-BDPP
(S,S)-BDPP
n-Pr
n-Pr
Ph
Ph
CH2CCH
CH2CCH
CH2CCH
CH2CCH
Tandem Silylformylation—Allylsilylation
OH
R2R1O
R1 R2
SiH O
R1 R2
SiH
HSi
H
t-But-Bu t-Bu
+ +
10 mol % CuCl10 mol % NaO-t-Bu10 mol % Ligand
Toluene, 12-24 h
BA
OH OH
R
i. 10 mol % ((PhO)3P)2Rh(CH3COOH)2.BF4,
CO, Benzene, 60 oC
ii.O
R
SiH
t-Bu
R = n-Pr, 55%, 78:22 drR = Ph, 38%, 90:10 dr
R = n-Pr, 80:20 drR = Ph, 90:10 dr
OH OH
R
i. 10 mol % ((PhO)3P)2Rh(CH3COOH)2.BF4,
CO, Benzene, 60 oC
ii.O
R
SiH
t-Bu
R = n-Pr, 44%, 79:21 drR = Ph, 43%, 88:12 dr
R = n-Pr, 80:20 drR = Ph, 88:12 dr
n-Bu4NF, THF, heat
n-Bu4NF, THF, heat
A
B
Outline Introduction - Basic Principle
Application In Carbon—Carbon bond forming Reactions - 4 Membered Silacycle - Aldol and Asymmetric Aldol Reaction - Addition To α,β-Unsaturated Carbonyl - Allylation Reaction - 5 Membered Silacycle - Asymmetric Allylation/Crotylation Reaction - Enantioselective Friedel-Crafts Alkylation Reaction - Enantioselective [3 + 2] Cycloaddition Reaction - Asymmetric Diels Alder Reaction - Tandem Reaction
Application In Natural Product Synthesis
Strain Release Chemistry With Al
Conclusion
Synthesis of (+)-SCH 351448
Bolshakov, S.; Leighton, J. L. Org. Lett. 2005, 7, 3809
- Isolated in 2000- Low-density Lipoprotein receptor
Retrosynthesis
O
OH O
CH3
O
HO
O
OHO
O
O
H3C
ONaO2C
H3C CH3
CO2H
H3C CH3
O
OBn OH
CH3
ONaO2C
H3C CH3
O
O
O
OBnOR
OH3C CO2H
H3C CH3
OO
OH
O
CH3CH3
OH3CH3C
R = TBS
A
B
C
RCM
3
4
1
2
5 Steps
B
C
A
BnO2CO
OBn OH OH
H3C CH3 CH35
Bolshakov, S.; Leighton, J. L. Org. Lett. 2005, 7, 3809
Forward Synthesis of Structure 5
Synthesis of (+)-SCH 351448
OO
1. ent-7, CH2Cl2, -10 oC
2.p-TsOH, Benzene, reflux
72% (2 steps)(93% ee)6 8
CHOt-BuO2C O
OBn
BnO2C
H3C CH3
O
H
9
O
OBn
BnO2C
H3C CH3
OH
CH3O
OBn
BnO2C
H3C CH3
O
CH3
SiH
12 11
10, CH2Cl2, 0 oC
80%, >20:1 dr
(Allyl)2Si(NEt2)H, CH2Cl2
3 Steps
Asymmetric Crotylationof Aldehyde
Asymmetric Allylationof Aldehyde
NSi
N
p-BrC6H4
p-BrC6H4
Cl 7 R = H10 R = CH3
R
Bolshakov, S.; Leighton, J. L. Org. Lett. 2005, 7, 3809
- 32 Total Steps- 2.1% Overall Yield
Forward Synthesis of Structure 5
Synthesis of (+)-SCH 351448
BnO2CO
OBn OH OH
H3C CH3 CH3
5
i. 5 mol% Rh(acac)(CO)2,
900 psi CO, Benzene, 65 oC
ii. n-Bu4NF, THF, reflux
69% (2 steps)
(+)-SCH 351448
O
OBn
BnO2C
H3C CH3
O
CH3
SiH
12
Steps
Tandem Silylformylation /Allylsilylation
Synthesis of Dolabelide D: Retrosynthesis
Park, P. K.; O’Malley, S. J.; Schmidt, D. R.; Leighton, J. L. J. Am. Chem. Soc. 2006, 128, 2796
- Isolated in 1997- Important cytotoxic agent
Dolabelide D
Total Synthesis of Dolabelide D
OAc O
CH3
OH OH
CH3
HO
CH3OH
H3C
OH
O
CH3 OAc
n-Pr
O
RCM
Esterification
2
3
OAc O
H3C
O
OHCH3
CH3 OAc
n-Pr
OH OH
CH3
OH
HO
1
CH3
Dolabelide D
A
A
B
B
CH3
CH3
PMBO O
4
O PMBO O
OH
CH3 CH3
5
+
Park, P. K.; O’Malley, S. J.; Schmidt, D. R.; Leighton, J. L. J. Am. Chem. Soc. 2006, 128, 2796
Synthesis of Fragment 2
11% overall yield from 6
Total Synthesis of Dolabelide D
i. 2 mol %
[Rh(acetone)2(P(OPh)3)2]BF4
CO, Benzene, 60 oC
ii. MeLi, Et2O, -78 to 23 oC
56%4:1 dr
HO Si HO
n-Pr
CH3
8
HSi
H
t-Bu
OH
n-Pr
+
4 mol % CuCl, 4 mol % NaO-t-Bu,
4 mol % (R,R)-BDPP, Benzene
95%4:1 dr
HSi
O
t-Bu
H3C
n-Pr
6 7 Silylformylation Crotylsilylation
O O OH CH3 OAc
n-Pr
CH3
2
8 steps
t-Bu CH3H3C
Synthesis of Dolabelide D
First Total Synthesis of Dolabelide D14 linear steps from 6 2% Overall yield
Park, P. K.; O’Malley, S. J.; Schmidt, D. R.; Leighton, J. L. J. Am. Chem. Soc. 2006, 128, 2796
Synthesis of Fragment 3
2 3+
4 steps
1
Dolabelide D
O
H
CH3 CH3
OPMB
CH3
O PMBO O
OH
CH3 CH3
ent-13, CH2Cl2;
NaH, PMBBr, THF, reflux
53%
6 Steps
12 14 5Asymmetric Crotylation
of aldehyde
4 5+
RO O
CH3
OH
CH3CH3
5 steps
3
OTESBMPOOAc
NSi
N
p-BrC6H4
p-BrC6H4
Cl
R10 R = H13 R = CH3
CH3
H
O10, CH2Cl2, - 20 oC
80 %98 % ee
CH3
OH
CH3
CH3
PMBO
2 Steps
O
9 11 4Asymmetric Allylation
of aldehyde
Synthesis of Polyketide like Macrolide
Tandem Silylformylation / Allylsilylation
Zacuto, M. J.; Leighton, J. L. Org. Lett. 2005, 7, 5525
H3C
O O OH OH OH
CH3 CH3 CH3
H3C CH3
H3C
OH
CH3 CH3
5 Steps
33% yield
1 2
O
O
OCH3
H3C
H3CO
HO
CH3
H3C
H3CO
HO
CH3
OBn
O
CH3
CH3
CH3
CH3
O
OCH3
H3C
O O OH OH OH
CH3 CH3 CH3
H3C CH3
5 steps52% yield
9 steps13% yield
2
3 4
Outline Introduction - Basic Principle Application In Carbon—Carbon bond forming Reactions - 4 Membered Silacycle - Aldol and Asymmetric Aldol Reaction - Addition To α,β-Unsaturated Carbonyl - Allylation Reaction - 5 Membered Silacycle - Asymmetric Allylation/Crotylation Reaction - Enantioselective Friedel-Crafts Alkylation Reaction - Enantioselective [3 + 2] Cycloaddition Reaction - Asymmetric Diels Alder Reaction - Tandem Reaction
Application In Natural Product Synthesis Strain Release Chemistry With Al
Conclusion
Strain Release Lewis Acidity: Al(III) Complexes
Catalyzed Asymmetric Acyl Halide - Aldehyde Cyclocondensation (AAC) Reactions
With Unsubstituted Acylhalide
Nelson, S. G.; Spencer, K. L. Angew. Chem. Int. Ed. 2000, 39, 1323
O
CH3Br
O
CH2CH2PhH+
10 mol% 1
i-Pr2NEt, CH2Cl2- 50 oC
96%
OO
CH2CH2Ph
97% ee
O
CH3X
O
R1H
+O
O
R1
X = Br, Cl
O
.
[R1CHO.Al(III)]
Al(III)-Catalyst
R3N
R3N
R3(H)N.X
N Al
N
N
Bn
CH3
i-Pri-Pr
SO2CF3F3CO2S
1
Nelson, S. G.; Kim, B-K.; Peelen, T. J. J. Am. Chem. Soc. 2000, 122, 9318
Strain Release Lewis Acidity: Al(III) Complexes
1.DMF Complex
Me
N1
N3
Al
N2114.0°
Plane angles(sum) = 358.6°
Me
N1
N3
Al
N297.5°
OH
NMe2
99.8°
N Al
N
N
Bn
CH3
i-Pri-Pr
SO2CF3F3CO2S
1
Active Catalyst Inactive Catalyst
Lacking a lewis basic residuein the ligand backbone
Nelson, S. G.; Kim, B-K.; Peelen, T. J. J. Am. Chem. Soc. 2000, 122, 9318
Ligand defineddistorted 4-coordinate geometryKey to reactivity
Strain Release Lewis Acidity: Al(III) Complexes
N Al N
CH3TfTf
4
N Al
N
N
Bn
CH3
i-Pri-Pr
TfTf
1
N Al
N
N
CH3
CH3TfTf
2
N Al
O
N
CH3TfTf
3
Strain Release Lewis Acidity: Al(III) Complexes
Nelson, S. G.; Kim, B-K.; Peelen, T. J. J. Am. Chem. Soc. 2000, 122, 9318
Inactive Catalyst
- Identical in coordination number and ligand electronics- Different in chelate size
Active Catalyst
NAl
N
NTfTf CH3
CH3
5 (inactive)
E1
Al
O
Al
O
Al
O
1 + RCHO
5 + RCHO
E2
Energy
NAl
N
N
R
TfTfMe
activeNAl
N
N
R
Tf TfMe
Inactive
N Al
N
N
Bn
CH3
i-Pri-Pr
SO2CF3F3CO2S
1 (active)
Origin of selectivity with 2
Strain Release Lewis Acidity: Al(III) Complexes
Nelson, S. G.; Zhu, C.; Shen, X. J. Am. Chem. Soc. 2004, 126, 14
N Al
N
N
CH3SO2CF3ArO2S
Ph
i-Pr i-Pr
Ar = 3,5-(CF3)2C6H3-
2
N Al
N
N
CH3SO2CF3ArO2S
Ph
i-Pr i-Pr
Ar = 4-(NO2)C6H4-
3
N Al
N
N
CH3
SO2O2S
R
CF3 Ar
N Al
N
N
CH3
SO2O2S
R
Ar CF3
H R1
OMajor Diastereomer
Second generation AAC catalyst
With Substituted Acylhalide
O
Br
O
PhH+
10 mol% 2
i-Pr2NEt, CH2Cl2- 25 oC
84%
OO
Ph
96% ee> 98:2 de (syn)
i-Pri-Pr
Total Synthesis of (-)-Malyngolide:
(−)-Malyngolide
- 4 Steps- 54% Overall Yield
Nelson, S. G.; Zhonghui, W. J. Am. Chem. Soc. 2000, 122, 10470
N Al
N
N
Bn
CH3
i-Pri-Pr
SO2CF3F3CO2S
1
OO
H3CnC9H19
OH
OHC
OBn
10 mol % 1, EtCOBr,
i-Pr2NEt, CH2Cl2, -50 oC OO
H3C
OBnOO
H3CnC9H19
OH85%
94% ee, 91:9 cis:trans
3 Steps
23
- An Antibiotic
Outline Introduction - Basic Principle Application In Carbon—Carbon bond forming Reactions - 4 Membered Silacycle - Aldol and Asymmetric Aldol Reaction - Addition To α,β-Unsaturated Carbonyl - Allylation Reaction - 5 Membered Silacycle - Asymmetric Allylation/Crotylation Reaction - Enantioselective Friedel-Crafts Alkylation Reaction - Enantioselective [3 + 2] Cycloaddition Reaction - Asymmetric Diels Alder Reaction - Tandem Reaction
Application In Natural Product Synthesis Strain Release Chemistry With Al
Conclusion
Conclusion
Release of strain of four or five membered silacycles in going from four coordinated distorted tetrahedral geometry to five coordinated trigonal bipyramidal geometry
Constraining silicon in a small ring (four or five) causes Lewis acidity
Enhanced lewis acidity of five membered silacycles containing heteroatom than four membered silacycles
Application of the Lewis acidity of these silacycles in various type of carbon-carbon bond forming reactions
Lewis acidity of some neutral electron-rich Al (III) complex due to distorted ground state coordination geometry imposed by the ligand backbone
Acknowledgement
Dr. Smith Dr. Borhan Dr. Jackson Dr. Walker Dr. Odom
Group Members: Abbas, Appi, Sulagna, Suzi
Friends: Sanjukta, Supriyo, Sampa, Partha, Luis
Thank You
