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Massachusetts Institute of Technology

Organic Chemistry 5.511

November 14, 2007Prof. Rick L. Danheiser

Unit 4

Stereocontrolled 1,2-Addition to Carbonyl Groups

 

Substrate Control: 1,2-Induction by Molecular Framework

 

Substrate Control: 1,3-Induction by Molecular Framework

 

Reagent Control: Reduction of Ketones

 

Reagent Control: Organozinc and Related Addition Reactions

  Addition of Alkyl, Aryl, Alkenyl, and Alkynyl Metal Compounds 

Lecture 13

 

Stereocontrolled Reduction of Ketones

BAlpine-Borane 

Mark Midland

UC Riverside

O

Al

O H

OMe

Li

BINAL-H 

Ryoji Noyori

Nagoya University

BH

CH3H3C

Satoru Masamune

MIT

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Stereocontrolled Reduction of Ketones

General Review

"Enantioselective Reduction of Ketones"

Itsuno, S. Organic Reactions 1998, 52 , 395

Reagent Control Strategies

(1) Itsuno-Corey Reduction ("CBS Reduction")

E. J. Corey 

See Merck Process,Org. Synth. 1996, 74 , 50

Reviews:

"Reduction of Carbonyl Compounds with Chiral Oxazaborolidine Catalysts: A New Paradigm for

Enantioselective Catalysis and a Powerful Synthetic Method" Corey, E. J.; Helal, C. J.

Angew. Chem. Int. Ed. 1998, 37 , 1987

"Recent Advances in the Synthetic Applications of the Oxazaborolidine-Mediated Asymmetric Reduction"Cho, B. T. Tetrahedron 2006, 62 , 7621

Case Study

Synthesis of

(R )-Fluoxetine (Prozac)

Corey, E. J.; Reichard, G. A.Tetrahedron Lett. 1989, 30 , 5207

NH2Me- Cl+

O

F3C

Shinichi Itsuno 

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(2) Noyori Asymmetric Hydrogenation

R. Noyori et al.

J. Am. Chem. Soc. 1988, 110 , 629

RZ:

OH

R

OH Z:

R

O Z:

R

OH Z:

RZ:

O

RZ:

OHH2

(R )-BINAP-Ru

H2

(S )-BINAP-Ru

H2

(R )-BINAP-Ru

H2

(S )-BINAP-Ru

Also see R. Noyori et al. Org. Synth. 1992, 71,1

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(2) Noyori Asymmetric Hydrogenation

Synthesis of C-D Spiroketal Unit of Spongistatin 1

Holson, E. B.; Roush, W. R. Org. Lett. 2002, 4 , 3719

Case Study

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Asymmetric Addition of Dialkylzinc Compounds to Aldehydes

Review: "Catalytic Asymmetric Organozinc Additions to Carbonyl Compounds"

  Pu, L.; Yu, H.-B Chem. Rev. 2001, 101, 757

OH

NMe2

OH

N

O

DAIB

MIB

W. A. Nugent

Ryoji Noyori in Stockholm (2001) Chem. Commun.  1999, 1369

Org. Synth.  2005, 82 , 87