applications of mukaiyama aldol reaction
TRANSCRIPT
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Applications of Mukaiyama
Aldol Reaction
Presented By :
Gurudutt DubeyM.Tech. (Pharm.) I Semester
Department of Pharmaceutical Technology (Process Chemistry)National Institute of Pharmaceutical Education and Research, Mohali, Punjab (India)
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INTRODUCTION
Mukaiyama Aldol Reactions :
O-Hydro-C-(α-acylalkyl)-addition
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Trimethylsilyl enol ether acts as an enolate in Lewis acid catalysed reaction.
It is considered as hydrogen equivalent which attacks on aldol hydroxyl group.
March J. et al. Advance Organic Chemistry 6th edition, 2007, 1351
R1R2Me3SiO
O
R3 R4Lewis Acid
CH2Cl2
OR2
R1
R3
R4
R1
OR2
R4
OSiMe3R3
H2O
OH
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Applications in Synthesis of Various Analogs
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4Org. Lett. 2012, 14, 1168-1171
Direct Use of Esters in the Mukaiyama Aldol Reaction Esters can be efficiently used in place of aldehyde
R OMe
O
OMe
OSiMe3
R OMe
OOH5 mol% InI3HSiMe2Ph
DCM, r.t., 2-12 h
R: Alkyl, Benzyl
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Synthesis of Functionalized Diazoacetoacetates from Diazoacetates
via Mukaiyama Reaction
Me3SiO
C2H5OAr
H ArN2
O
O OO
N2C2H5O
OH
3 mol% Sc(OTf)3
60-80%
DCM, rt
Diazo Decomposition of Mukaiyama-aldol Adduct
Org. Lett 2008, 10(8), 1605-1608
Ar
OO
N2
C2H5O
OTBS
1 mol% Rh2(OAc)3
DCM, reflux
OO
H OTBSR OTBS
R COOC2H5H COOC2H5
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Enantioselective catalytic Mukaiyama reaction in aqueous media
Org. Biomol. Chem. 2004, 2, 3401-3407
PhMe
OTMS
PhCOPh
OH
Me
PhCHO
Ga(OTf)3 + L*(20 mol%)
Triton X-100 (3 mol%)
H2O, 0 0C, 72 h
41% yield, 84% ee
N N
But
OH
Ph
HOPh
Ph
OHPh
L* =
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VINYLOGOUS MUKAIYAMA ALDOL REACTION
Org. Lett. 2007, 9(26), 5667-5639
R
O
OMe
OTBS
NH
O
NB
O
Ph
Ts OMe
O
R
OH
iPrOH
R= Alkyl, Aryl 99% ee
• For one step synthesis of δ-Hydroxy-α,β-unsaturated carbonyl compounds.
• Catalyst: Tryptophane-based B-phenyloxazaborolidinone
• Isopropyl alchol is used to improve the yield of enantioselective product.
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Vinylogous Mukaiyama Aldol Reaction to Natural Product Synthesis
Intermediate formation in synthesis of Khafrefungin, an antifungal agent
8Org. Lett. 2007, 9(5), 849-852
N O N O
O OO
Me
R2
OH
Me
N O
OO
Me
R2
OH OTBS
Me
R1
R1=H
R2CHOTiCl4
R1=Me
R2CHOTiCl4
1,6,7- Remote Asymmetric Induction1,7- Remote Asymmetric Induction
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Vinylogous Mukaiyama Aldol Reaction to Natural Product Synthesis
Intermediate formation in synthesis of Khafrefungin, an antifungal agent
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H3C(H2C)9O
Me
OH
Me Me Me
O
Me Me
OOH
OH
OH
O
HO
Org. Lett. 2007, 9(5), 849-852
Khafrefungin
N O N O
O OO
Me
R2
OH
Me
N O
OO
Me
R2
OH OTBS
Me
R1
R1=H
R2CHOTiCl4
R1=Me
R2CHOTiCl4
1,6,7- Remote Asymmetric Induction1,7- Remote Asymmetric Induction
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Asymmetric Synthesis of anti-β-Hydroxy-α-Amino Acid Derivatives Catalytic Enantio- and Diastereoselective Aldol Reactions of Glycine-Derived
Silicon Enolate with Aldehydes
R H
O
R OMe
O
OMe
OSiMe3
NF3C
OSiMe3Catalyst
toluene/ tBuOMe-20 0C, 12 h
0.5 M aq. KHSO4
OH
NHCOCF3
Catalyst:1. Zr(OtBu)4, ligand2. H2O (cat.), r.t., 1h
I
OH
OH
I
I
I
Ligand:
J. Am. Chem. Soc. 2004, 126, 9192-9193
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H
MeO
H H8
910
1112
13
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New approach toward the synthesis of steroid skeletons using
Mukaiyama reactions
(D)-Steroid Skeleton :
Tetrahedron 2006, 62,1726–1742
MeO
OSiR3
MeO
O
O
TrSbCl6C8-C14
bond formation
OSiR3
8
910
1112 13
14
Intermediary step
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Thank You