chiral allylsilanes as enantioselective allylation reagents for aldehydes focusing on work by james...
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Chiral Allylsilanes as Enantioselective Allylation Reagents for Aldehydes
Chiral Allylsilanes as Enantioselective Allylation Reagents for Aldehydes
Focusing on work by
James BullGroupe Charette, Réunion de littérature, 4 Décembre 2007
James S. Panek and James L. Leighton
SiR3 R
RRSi
L**L
LR
R
Outline
I. Introduction to allylation chemistryStereocontrol features for allylsilanesIntroduce SE2’ reactivity/stereospecificity Hyperconjugation, Open Transition States
II. James S. Panek1. Background/ Concept2. Aldehyde Crotylation3. Synthesis of chiral allyl silanes4. Use in complex molecule synthesis
III. James L. Leighton1. Background/ Concept2. Synthesis of chiral allyl silanes3. Allylation/Crotylation4. Imine electrophiles
Si
L**L
LR
R
SiR3 R
RR
The importance of allylation/crotylation chemistry
O O
MO
R
SE2' OH
Rcontrol ofchirality
R1
R2 R1 R2
OOH
RR1 R2
H
Common (Excellent) Enantioselective Methods
Brown Roush
Excellent enantio/diastereocontrol Unstable to storagePrepared in situUsed at low temperature
B R 2
R1O
O
iPrCO2
iPrCO2
OB
L*
L*
R
R2
R1
Well defined cyclic TS’s (Type I class)
L*2B Me
L*2B
Me
OH
R
OH
R
Me
Me
B R 2
R1
Common (Excellent) Enantioselective Methods
Keck
Lewis Base catalysed enantioselective allylation
Denmark, S. E.; Fu, J. Chem. Rev. 2003, 103, 2763
SnBu3
O
RR1
R
R1OH
OH
OH
Ti(OiPr)4
2 eq
4 A MS, CH2Cl2rt, 1h
SiCl3
O
R R
OHTi(OiPr)4
4 A MS, CH2Cl2R2
R1
5 mol %
PN
N N N
N
NP
5
R2 R1
HHHH
OO
Allylsilanes
SE2’ antiStereospecific
Stereocontrol??• New Chiral Centre• Double bond geometry• When E+ = aldehyde, diastereoselectivity
R1R
ROH
R3
SiR3
R1
R
R
E+
R1R
RELewis Acid
What is SE2’ reactivity??What is SE2’ reactivity??
Stereospecific ≠ 100% stereoselective Defined by mechanism
Determined by Structure/steric effectsConformation effects
What is a stereospecific reaction??What is a stereospecific reaction??
SE2’ reactivity
SN2
InversionStereospecific
A
CBX
N
SE2’ reactivity
SN2
InversionStereospecific
A
CBX
N
SN1 AB
C*N
Non stereospecificMay be stereoselective
SE2’ reactivity
SN2
InversionStereospecific
A
CBX
N
SN1 AB
C*N
Non stereospecificMay be stereoselective
SN2’Direct SN2 usually fasterStereospecifically Syn (depending on nucleophile)
LG
Nu
Stork:
OCOAr
NHN
OCOAr
N
Stork, G.; White. W. N. J. Am. Chem. Soc. 1956, 78, 4609.
SE2’ reactivity
SN2
InversionStereospecific
A
CBX
N
E+A
CBM
A
CBM
Grignards: non stereospecificLi, inversion or retention depending on electrophile
stereodefined C-M bonds
A
CBE M
Inversion
RetentionE
SE2
MeO
N
OtBuO
Ph
HH BuLi
sparteine
MeO
N
OtBuO
Ph
LiH
MeO
N
OtBuO
Ph
H
MeO
N
OtBuO
Ph
H
Br
O
OMe
CO2Me
CHOCHO
Retention
Inversion
Park, Y. S.; Beak. P. J. Org. Chem. 1997, 62, 1574.
SE2’ reactivity
SN2
InversionStereospecific
A
CBX
N
SN2’ LG
Nu
Stereospecifically SYNDirect SN2 usually faster
SE2 A
CBE M
Inversion
Retention
SE2’M
E+
For M = Si Stereospecifically ANTIM = Si, B, Mg, Sn, Ti, Cr, Zn, ….
Stereocontrol for allylsilanes
Parallel bonds for max interaction
Hyperconjugation: -conjugation
R3Si
R H
R2
R1
R3Si
RH
R2
R1
R3Si
R H
R2R1
E
ANTIR
H
R2R1
E
trans
RRR> >
H CH3 M
closer in energypoor energy matchpoor geometry
< <<
If there is no clearly prefered ground state conformationstereoselectivity will be reduced But reaction still occurs stereospecifically anti
Hg HgSiR3
Stereocontrol for allyl silanes
R3Si
R H
R2
R1
R3Si
RH
R2
R1
R3Si
R H
R2R1
E
ANTIR
H
R2R1
E
trans
No preorganisation by Lewis Acid
Open Transition State (Type II class)
SiR3
R1
R2
R
Lewis Acid
R1R2
ROH
R3
O
H R3
LA
Open TS for crotylsilane reagents
E-silane
Z-silane
SYN diastereoselective
SYN diastereoselective ANTI diastereoselective
ANTI diastereoselective
Antiperiplanar Transition States for crotyl silanes
Relative energy differences between antiperiplanar and synclinal TS are negligible
SYN product preferred
TS may adopt an antiperiplanar or synclinal arrangement
Open TS for crotylsilane reagents
Both antiperiplanar and synclinal TS predict syn selectivity
Synclinal Transition States
Z-silane
E-silane
SYN diastereoselective ANTI diastereoselective
Outline
I. Introduction to allylation chemistry,Stereocontrol features for allylsilanesIntroduce SE2’ reactivity/stereospecificity Hyperconjugation, Open Transition States
II. James S. Panek1. Background/ Concept2. Aldehyde Crotylation3. Synthesis of chiral allyl silanes4. Use in complex molecule synthesis
III. James L. Leighton1. Background/ Concept2. Synthesis of chiral allyl silanes3. Allylation/Crotylation4. Imine electrophiles
Si
L**L
LR
R
SiR3 R
RR
James S. Panek
b. 19561979 BSc Chemistry (SUNY Buffalo)1984 PhD Medicinal Chemistry (Kansas) with Dale Boger1984-86 Post Doc (Yale) with Danishefsky1986 Boston University
Chiral E-crotylsilane:Well behaved SE2’ Anti additionComplete transfer of chiralityProvides easily functionalised products
Able to control reaction pathway by control of temperature and Lewis acid
RCO2Me
SiMe2Ph
R X
Crotylation using syn-selectivity
Panek, J. S.; Yang. M. J. Am. Chem. Soc. 1991, 113, 6594.
Complete chirality transfer from silane, no other diastereoisomers observedAnti SE2’E double bondSyn Selective
OMe
OMe 92%, 40:1, 95% ee
OMe
OMe
MeCO2Me
SiMe2Ph
OMeO
OMe
CO2MeMe
OMe
OMe
Ar OMe
TMSOTf
OMe
CO2Me
OMe
Major
Minor
90%, 13:1, 95% ee–78 ºC, CH2Cl2
Crotylation using Syn-selectivity
Panek, J. S.; Yang. M. J. Org Chem. 1991, 56, 5755.
OMe
CO2Me
86%, 30:1, 96% ee
BnO
OMe
CO2Me
OMe
O
70%, 30:1, 96% ee
OMe
CO2Me
OMe
BnO
96%, 20:1, 96% ee
MeCO2Me
SiMe2Ph
MeOMe
CO2Me
Me
TMSOTf
88%, 30:1, 96% ee
–78 ºC, CH2Cl216 h
OMe
OMeBnO BnO
Crotylation using Syn-selectivity
Panek, J. S.; Yang. M.; Solomon J. S. J. Org. Chem. 1993, 58, 1003.
Form oxonium in situOMe
CO2Me
OAc
O
85%, 20:1
OBn
CO2Me
OAc
87%, 20:1
OBn
CO2Me
OAc
BnO
PdCl2 (20 mol%)CH2Cl2, rt
OBn
CO2MeBnO
OAc
36 h
86%
Pd catalysed allylic transposition to form 1,3-diols
MeCO2Me
SiMe2Ph
OAc OBn
CO2Me
OAcTMSOTf
51%, 20:1
–78 ºC to –35 ºC CH2Cl2
BnOO
BnO
TMSOBn
complete preservation of chirality1,3-syn diol
MeCO2Me
SiMe2Ph
OAcTMSOTf
–78 ºC to –70 ºC CH2Cl2
OMe
CO2Me
OAc PdCl2 (20 mol%)CH2Cl2, rt
OMe
CO2MeBnO
OAc
36 h
96%
OMe
BnO BnO
54%, 20:1
OMe
Acyclic Diastereoselectivity - Reversing Syn Selectivity
Panek, J. S.; Cirillo, P. F. J. Org. Chem. 1993, 58, 999.
OH
CO2Me
6.5:1syn:anti
BnOBF3.OEt2, –78 ºCMe
CO2Me
SiMe2Ph
O
BnO
Me
Re face attack
MgBr2.OEt2, –25 ºCMe
CO2Me
SiMe2Ph
O
BnO
MeOH
CO2Me
1: 12.2syn:anti
BnO
Si face attack
Chiral Aldehydes - Double stereodifferentiation
Chirality of the aldehyde controls the absolute stereochemistry of the oxygen bearing stereogenic centre.Chelation control with OBn, Felkin control with OTBDPS
R = Me, 64%, 10:1R = Et, 35%, 15:1
R = Me, 85%, 1:30R = Et, 69%, 1:10
Syn:Anti
R = H, 90%, >30:1R = Me, 79%, >30:1R = Et, 74%, 15:1
R = Me,98 %, 1:8R = Et, 79%, 1:10
MeCO2Me
SiMe2Ph
RO
BnO
TiCl4 (1.1 eq)CH2Cl2, –78 ºC
OH CO2MeR
BnO
MeCO2Me
SiMe2Ph
RO
BnO
TiCl4 (1.1 eq)CH2Cl2, –78 ºC
OH CO2MeR
BnO
OH CO2MeR
TBDPSO
O
TBDPSO
O
TBDPSO MeCO2Me
SiMe2Ph
R
MeCO2Me
SiMe2Ph
R TiCl4 (1.1 eq)CH2Cl2, –78 ºC
TiCl4 (1.1 eq)CH2Cl2, –78 ºC
OH CO2MeR
TBDPSO
Chiral Aldehydes - Double stereodifferentiation
Jain, N. F.; Takenaka, N.; Panek, J. S. J. Am. Chem. Soc. 1996, 118, 12475.
O
TBDPSOMe
CO2Me
SiMe2Ph
R TiCl4 (1.1 eq)CH2Cl2, –78 ºC
OH CO2MeR
BnO
O
TBDPSOMe
CO2Me
SiMe2Ph
R TiCl4 (1.1 eq)CH2Cl2, –78 ºC
OH CO2MeR
TBDPSO
Chiral Aldehydes - 1,3-induction?
Jain, N. F.; Takenaka, N.; Panek, J. S. J. Am. Chem. Soc. 1996, 118, 12475.
Silane reagents override 1,3-induction of the chiral aldehydePredisposed to local Felkin induction to determine hydroxy stereochemistry
MeCO2Me
SiMe2Ph
R
MeCO2Me
SiMe2Ph
R
MeCO2Me
SiMe2Ph
R
MeCO2Me
SiMe2Ph
R
TiCl4 (1.1 eq)CH2Cl2, –78 ºC
TiCl4 (1.1 eq)CH2Cl2, –78 ºC
TiCl4 (1.1 eq)CH2Cl2, –78 ºC
TiCl4 (1.1 eq)CH2Cl2, –78 ºC
Synthesis of chiral silanes
Johnson-Claisen
Complete preservation of chirality
Beresis, R. T.; Solomon J. S.; Yang. M.; Jain, N. F.; Panek, J. S.; Org. Synth. 1998, 75, 78.Panek, J. S.; Yang. M. J. Am. Chem. Soc. 1991, 113, 6594
HOH
HSiPhMe2 (1.1 eq)THF, 50 ºC
SiO
Si
SiPhMe2
OHPttBu3P
Lipase (0.5 eq)
SiPhMe2
OH
SiPhMe2
OAc
vinyl acetate
86%
46%
48%
MeCO2Me
SiMe2Ph
SiPhMe2
OH
(MeO)3CCH3cat. propionic acid
toluenereflux
SiPhMe2
O
OMe 86%96% ee
Synthesis of chiral silanes
Enolate
Ireland-Claisen
Sparks, M. A.; Panek, J. S. Org. Chem. 1991, 56, 3431. Panek, J. S.; Yang. M.; Solomon J. S. J. Org. Chem. 1993, 58, 1003Panek, J. S.; Beresis, R.; Xu, F.; Yang, M. Org. Chem. 1991, 56, 7341.
SiPhMe2
OH
Me SiPhMe2
O
O
R
HO
O
R
MeCO2Me
SiMe2Ph
R
DCCDMAP
1. LDA, TMSCl
–78 ºC to rt
R = Me 1:12 81%R = OH >25:1 65%R = OMe 23:1 81%
syn:anti
LDA, HMPS, TMSCl R = Me 16:1 69%
2. SOCl2/MeOH
MeCO2Me
SiMe2Ph
MeCO2Me
SiMe2Ph
R
Anti:synMeI 100:1BnBr 75:1
LDA
electrophile
.
.
Synthesis of chiral silanes
Huang, H.; Panek, J. S. Org. Lett. 2003, 5, 1991.
OHPhMe2Si
D-(–)-DETTi(OiPr)4,MS
CH2Cl2, –20 ºC
91%, 97% eeOHPhMe2Si
O1. TMSCl, Et3N
DMAP, CH2Cl2, –20 ºC
2. MgBrCuI, THF–50 ºC
OTMS
OH
SiMe2Ph
OAc
OH
SiMe2Ph
1. Citric acidMeOH
2. Ac2O, pyrDMAP, CH2Cl2
85%
71%
Synthesis of Oleandolide - Retrosynthesis
Hu, T.; Takenada; N.; Panek, J. S. J. Am. Chem. Soc. 1999, 121, 9229.Hu, T.; Takenada; N.; Panek, J. S. J. Am. Chem. Soc. 2002, 124, 12806.
MeCO2Me
SiMe2Ph
MeCO2Me
SiMe2Ph
R
R-2 S-3, R = HS-4, R = Me
PO
OP OP
[M]
OP
O
OP OP
MeH
7 81 13
Synthesis of Oleandolide
Hu, T.; Takenada; N.; Panek, J. S. J. Am. Chem. Soc. 1999, 121, 9229.Hu, T.; Takenada; N.; Panek, J. S. J. Am. Chem. Soc. 2002, 124, 12806.
90%, >30:1 Syn:AntiFelkin approach
TBDPSO H
O
TiCl4, CH2Cl2–78 ºC to –35 ºC
TBDPSO
OH CO2MeMe
CO2Me
SiMe2PhR-2
1. 2% HCl/MeOH, 92%2. tBuSi(OTf)2, 2,4-lutidine3. O3, Me2S, MeOH/pyr (90%, 2 steps)
O O
O
SitBu tBu
H
TiCl4, CH2Cl2–78 ºC to –35 ºC
MeCO2Me
SiMe2PhS-3
O OSi
tBu tBu
OH CO2Me
87%, >30:1 Anti:SynFelkin approach
TBDPSO
O O
I
1. O3, Me2S, MeOH/pyr2. NaBH4, MeOH,90% (2 steps)3. I2, PPh3, Imid, 98%
TBDPSO
O O CO2Me1. HF.py2. TBDPSCl, 92% (2 steps)3. Me2C(OMe)2, PPTS, 99%
Synthesis of Oleandolide
TBSOH
O
BF3.Et2O, CH2Cl2
–78 ºC to 0 ºC
HO
OH CO2MeMe
CO2Me
SiMe2PhR-2
82%, >30:1 Anti:Syn
TBSO
OTBS
O
1. TBSOTf, 2,6-lutidine2. O3,Me2S (93% 2 steps)
TiCl4, CH2Cl2–50 ºC
MeCO2Me
SiMe2PhS-3
CO2Me
Me
TBSO
TBSO OH
82%, >20:1 Syn:Anti
O
TBSO
TBSO OHO3, Me2S90%
1. Me4NBH(OAc)3MeCN, AcOH, –20 ºC, 89%2. PhCH(OMe)2, CSA, 89%
3. HF.py, py, 96%4. Dess Martin 95%
O
O
TBSO O
Ph
Hu, T.; Takenada; N.; Panek, J. S. J. Am. Chem. Soc. 1999, 121, 9229.Hu, T.; Takenada; N.; Panek, J. S. J. Am. Chem. Soc. 2002, 124, 12806.
Synthesis of Oleandolide
TBDPSO
O O O
O
TBSO O
Ph
tBuLi
TBDPSO
O O
I
O
O
TBSO O
Ph
Oleandolide
Hu, T.; Takenada; N.; Panek, J. S. J. Am. Chem. Soc. 1999, 121, 9229.Hu, T.; Takenada; N.; Panek, J. S. J. Am. Chem. Soc. 2002, 124, 12806.
Alternative Reaction Pathways
Panek, J. S.; Yang, M. J. Am. Chem. Soc. 1991, 113, 9868.
1,2 silyl migration competes with elimination
OH
CO2Me
6.5:1syn:anti
BnOBF3.OEt2, –78 ºCMe
CO2Me
SiMe2Ph
O
BnO
Me
If allowed to warm..
Me
CO2Me
SiMe2Ph
O
BnO
Me
Me
CO2Me
O
BnO
MeSiR3
F3BF3B
BF3.OEt2,Me
CO2Me
SiMe2Ph
O
BnO
Me
OBnO CO2Me
SiMe2Ph
H H
80%, 30:1 syn:anti, 96%de
–78 ºC to –30 ºC
Same concepts apply….
Masse, C. E.; Panek. J. S. Chem. Rev. 1995, 95, 1293, Fleming, I.; Barbero, A.; Walter, D. Chem. Rev. 1997, 97, 2063. Huang, H.; Panek, J. S. J. Am. Chem. Soc. 2000, 122, 9836
RCO2Me
SiMe2Ph
R Z
NR'O2C
HR
O
HR
LA
LA
CO2Me
Me
OH
R
CO2Me
Me
NHCO2R'
R
CO2MeE
Me
E+
XRCO2Me
SiMe2Ph
H H
Me
O
HCHO
Me
R3Si
MeO2C
O
HR
OH H
RMeO2C
Me
Outline
I. Introduction to allylation chemistry,Stereocontrol features for allylsilanesIntroduce SE2’ reactivity/stereospecificity Hyperconjugation, Open Transition States
II. James S. Panek1. Background/ Concept2. Aldehyde Crotylation3. Synthesis of chiral allyl silanes4. Use in complex molecule synthesis
III. James L. Leighton1. Background/ Concept2. Synthesis of chiral allyl silanes3. Allylation/Crotylation4. Imine electrophiles
Si
L**L
LR
R
SiR3 R
RR
James L. Leighton
Si
L**L
LR
R
b. 19641987 BSc Chemistry (Yale)1994 PhD Chemistry (Harvard) with David Evans1994-96 Post Doc (Harvard) with Eric Jacobsen1996 Columbia University
Cyclic transition state
Concept
B reagents - Type I cyclic TS Si Reagents - Type II open TS
OB
L*
L*
R
R2
R1
Make Si more Lewis-acidic to encourage a cyclic transition state
OSi
L*
L*
R
R2
R1
“Strain-Release Lewis Acidity”
Myers and Denmark Utimoto
Strained Silacycles: New reagents for allylation
Supports idea that ring strain is importantRing strain still exists due to long Si-O and short C-O bondsProceeds via cyclic TS
OSi
O
Cl
O
HPh
Tol
rt
OH
Ph
52%Uncatalysed
O
HPh
Tol
rt
O
HPh
Tol
rt
OSi
O
Cl
SiCl
O
O
N. R.
N. R.
Kinnaird, J. W. A.; Ng, P. Y.; Kubota, K.; Wang, X.; Leighton, J. L, J. Am. Chem. Soc. 2002, 124, 7920. Zhang, X.; Houk, K. N.; Leighton, J. L, Angew. Chem. Int. Ed. 2005, 44, 938.
Synthesis of Chiral Allyl Silanes
Screen chiral 1,2-diols, amino-alcohols and diamines
NSi
O
Cl
Ph
Me
Easily prepared Stable to storageConvenient work-up
Mixture of diastereoisomersInterconvert? React in same way?
Kinnaird, J. W. A.; Ng, P. Y.; Kubota, K.; Wang, X.; Leighton, J. L, J. Am. Chem. Soc. 2002, 124, 7920.
NSi
O
Cl
Ph
Me
NH
OHPh
Me
SiCl3
DBU, CH2Cl2
88% 2:1 dr
Scope - optimised conditions
Table 1
Kinnaird, J. W. A.; Ng, P. Y.; Kubota, K.; Wang, X.; Leighton, J. L, J. Am. Chem. Soc. 2002, 124, 7920.
NSi
O
Cl
Ph
Me (s,s)R
O
H
Toluene–10 ºC, 2h
R
OH
Diamine ligand
NSi
N
Cl
Br
Br
Best eeBr confers crystallinityStable solid (moderate air sensitivity)Straightforward synthesisSingle crystallisation to purify
Kubota, K.; Leighton, J. L, Angew. Chem. Int. Ed. 2003, 42, 946.Zhang, X.; Houk, K. N.; Leighton, J. L, Angew. Chem. Int. Ed. 2005, 44, 938
Scope
Excellent ee“among highest observed for this reaction”CH2Cl2 best solvent for allylation. Much longer reaction time 20h vs 2h
Aromatic Substrates
Aliphatic Substrates
NSi
N
Cl
pBrPh
pBrPh
R
O
H
CH2Cl2–10 ºC, 20h
R
OH
(R,R)
Kubota, K.; Leighton, J. L, Angew. Chem. Int. Ed. 2003, 42, 946
Scope - Chiral substrate
Chiral substrate:
Overrides 1,3 induction of chiral aldehyde
Kubota, K.; Leighton, J. L, Angew. Chem. Int. Ed. 2003, 42, 946
NSi
N
Cl
pBrPh
pBrPh
(R,R)
CH2Cl2–10 ºC, 20h
OH
(R,R) Ph
OBn
O
Ph
OBn
OH
Ph
OBn
86%, 95:5 dr
86%, 98:2 dr(S,S)
Crotylation - Cis reagent
Hackman, B. M.; Lombardi, P. J.; Leighton, J. L, Org. Lett. 2004, 6, 4375
Syn:Antidr >15:1
NSi
N
Cl
pBrPh
pBrPh
R
O
H
CH2Cl20 ºC, 20h
R
OH
(R,R)
1.1 equiv
Crotylation - Trans reagent
Hackman, B. M.; Lombardi, P. J.; Leighton, J. L, Org. Lett. 2004, 6, 4375
NSi
N
Cl
pBrPh
pBrPh
R
O
H
CH2Cl20 ºC, 20h
R
OH
(R,R)
Anti:Syndr >25:1
Reagents are crystalline solids but moisture sensitive - storable eg in glove boxHigh MW diamine. - 90% recoverable
Imine electrophiles - Aldimine allylation
NSi
O
Cl
Ph
Me (s,s)R
N
H
CH2Cl210 ºC, 16h
NH
O
1.5 eq
R
HNNH
O
Requires NHAc directing group
Berger, R.; Rabbat, P.M.; Leighton, J. L, J. Am. Chem. Soc. 2003, 125, 9596.
Single recrystallisation allowsaccess to enantiopure compounds
Imine electrophiles - Ketimine allylation
Berger, R.; Duff, K.; Leighton, J. L, J. Am. Chem. Soc. 2004, 126, 5686.
NSi
O
Cl
Ph
Me (s,s) R1
N
R2
CHCl340 ºC, 24h
NH
O Ph
R1
NHNHBzR2
Imine electrophiles - Aldimine crotylation
Trans reagent Syn product89%, 95:5, 97%22
Berger, R.; Rabbat, P.M.; Leighton, J. L, J. Am. Chem. Soc. 2003, 125, 9596.Berger, R.; Duff, K.; Leighton, J. L, J. Am. Chem. Soc. 2004, 126, 5686.
NSi
O
Cl
Ph
Me (s,s) R
N
H
CH2Cl210 ºC, 16h
NH
O Ph
R
HNNH
O Ph
Me
Imine electrophiles - directing groups
NSi
O
Cl
Ph
Me (s,s)R
N
H
CH2Cl2rt, 16h
HO
R
HN
HOR1
R2
R1 R2
HN
HO
HN
HO
HN
HO
64%98:2 dr98%ee
85%92%ee
83%96%ee
NSi
O
Cl
Me N
HN
R
NR1
N
HN
HNR1Toluene
23 ºC R
N
HN
HN
80%87%ee N
HN
N
71%88%ee
O
86%91%eeN
HN
HNMe
Rabbat, P. M.; Valdez, S. C.; Leighton, J. L, Org. Lett. 2006, 8, 6119.Perl, N. R.; Leighton, J. L, Org. Lett. 2007, 9, 3699.
Imine electrophiles - Cinnamylation
Huber, J. D..; Leighton, J. L, J. Am. Chem. Soc. 2007, 129, 14552.
NSi
O
Cl
Ph
Me
R
N
H
HO
Ph
DCE, reflux
R
N
H
DCE, reflux
HO
R
HN
Ph
R
HN
Ph
ArAr
Imine electrophiles - Cinnamylation
Huber, J. D..; Leighton, J. L, J. Am. Chem. Soc. 2007, 129, 14552.
NSi
O
Cl
Ph
Me
R
N
H
HO
Ph
DCE, reflux
R
N
H
DCE, reflux
HO
R
HN
Ph
R
HN
Ph
ArAr
Summary
Panek: Chiral allyl silanes for acyclic stereocontrol
Leighton: Chiral allyl silanes allowing cyclic stereocontrol
MeCO2Me
SiMe2Ph
RO
BnO
TiCl4 (1.1 eq)CH2Cl2, –78 ºC
OH CO2MeR
BnO
85%, dr 1:30
NSi
N
Cl
pBrPh
pBrPhO
H
CH2Cl2–10 ºC, 20h OH
(R,R)
TBSO TBSO
61%, 98% ee