Massachusetts Institute of TechnologyOrganic Chemistry 5.512

December 3, 2007Prof. Rick L. Danheiser

Unit 6

Stereocontrolled Aldol Reactions

Overview of the Stereochemistry of the Aldol Reaction and Substrate Control

Reagent Control: Chiral Auxiliary Strategies

Reagent Control: Chiral Controller Strategies

Reagent Control: Chiral Lewis Acid Catalyzed Aldol Reactions

David A. EvansSatoru Masamune Clayton H. Heathcock

Lecture 18

R1OH

R2

O

Z234

The Aldol Retron

Alexsander Borodin

General References on Aldol Chemistry

"Catalyzed Enantioselective Aldol Additions of Latent Enolate Equivalents"Nelson, S. G. Tetrahedron: Asymmetry 1998, 9, 357-389.

"Diastereoselection in Lewis-Acid-Mediated Aldol Additions"Mahrwald, R. Chem. Rev. 1999, 99, 1095-1120.

"The Catalytic Asymmetric Aldol Reaction"Machajewski, T. D.; Wong, C.-H. Angew. Chem. Int. Ed. 2000, 39, 1352-1374.

"Recent Developments in Asymmetric Aldol Methodology"Franklin, A. S.; Paterson, I. Contemp. Org. Syn. 1994, 1, 317-338.

"Asymmetric Aldol Reactions Using Boron Enolates"Cowden, C. J.; Paterson, I. Org. React. 1997, 51, 1.

"Recent Advances in Asymmetric Aldol Addition Reactions"Carreira, E. M. In Catalytic Asymmetric Synthesis, Second Edition; Ojima, I., Ed.; Wiley-VCH, 2000, pp 513-541.

"Aldol Reactions: Methodology and Stereochemistry"Carreira, E. M. In Modern Carbonyl Chemistry; Otera, J., Ed.; Wiley-VCH, 2000, pp 227-248.

"Stereoselective Aldol Reactions in the Synthesis of Polyketide Natural Products"Paterson, I.; Cowden, C. J.; Wallace, D. J.; In Modern Carbonyl Chemistry; Otera, J., Ed.; Wiley-VCH, 2000, pp 249-298.

Modern Aldol Reactions (2 Vols); Mahrwald, R., Ed.; Wiley-VCH, 2004.

"Current Progress in the Asymmetric Aldol Addition Reaction"Palomo, C.; Oiarbide, M.; Garcia, J. M. Chem. Soc. Rev. 2004, 33, 65.

"Catalytic Enantioselective Aldol Addition Reactions"Carreira, E. M.; Fettes, A.; Marti, C.Org. React. 2006, 67, 1.

"Modern Aldol Methods for the Total Synthesis of Polyketides"Schetter, B.; Mahrwald, R.Angew. Chem. Int. Ed. 2006, 45, 7506

Aldol Reaction Stereochemistry: Recent Examples

Evans, D. A.; Siska, S. A.; Cee, V. J. Angew. Chem. Int. Ed. 2003, 42, 1761. See alsoEvans, D. A. et. al J. Am. Chem. Soc. 2006, 128, 2920

II. Chiral Auxiliary Strategies

OBO

H

R

N

Me

Bu

Bu

O

O H

2,3-Syn Aldols

Evans OxazolidinoneBoron Enolates

Gage, J. R.; Evans, D. A.Org. Synth. 1990, 68, 83

Review"Asymmetric Aldol Reactions Using Boron Enolates"Cowden, C. J.; Paterson, I. Organic Reactions 1997, 51, 1

2,3-Anti Aldols

D. A. Evans et al.J. Am. Chem. Soc. 2002 124, 392

and Org. Lett. 2002, 4, 1127

(1) Evans Dones

(2) Oppolzer Sultams

NS

OO OSiR3

H

R

OH

Me

L.A.

(3) Masamune Esters

Review"Boron-Mediated Aldol Reaction of Carboxylic Esters"Abiko, A. Acc. Chem. Res. 2004, 37, 387see also Org. Synth. 2002, 79, 109 and 116