Evans Aldol Reaction - Alfa Chemistry

Introduction

Aldol Addition Reaction: Traditionally involves the self-addition of aldehydes or ketones under acid or base catalysis, producing β-hydroxycarbonyl compounds.
Cross Aldol Addition: Reaction between different aldehydes (or ketones).
Aldol Condensation: Conversion of aldehydes or ketones to α,β-alkenals (or ketones) through dehydration.
Challenges: Under typical conditions, issues arise with chemical selectivity, regioselectivity, and stereoselectivity, resulting in various regioisomers and stereoisomers.

Preformed enol anions: Utilized for regioselective aldol reactions.
Asymmetric Aldol Addition: Developed by Evans using chiral auxiliary group N-acyloxazolone, enhancing selectivity.
Catalysis: Boron trifluoromethanesulfonate catalysis leads to the Evans-syn product.
Stereoselectivity: Using different chiral groups and Lewis acid conditions allows for different stereoisomers.

Kinetic Aldol Addition: 2-enolate and aldehydes yield syn products; E-enolate and aldehydes yield anti products.
Evans Aldol Addition: Produces Z-enolate, favoring syn products.
Zimmerman-Traxler Model: Describes the transition state contributing to high selectivity.
Transition State: Six-membered ring chair formed by boron atom complexation with oxygen atoms.
Product Formation: Evans syn product formed when aldehyde attacks from the less hindered Re plane.

Natural Products Synthesis: Widely used in synthesizing complex natural products.
- Example: FD-891 synthesis illustrates the importance of Evans aldol addition.
Hapalosin Synthesis:
- Details: Aldol reaction between n-octanaldehyde and chiral imide resulted in syn-aldol with high yield.
- Outcome: Indicates relevance in compounds enhancing taxol accumulation in cells.

Key publications by Evans and others in the Journal of the American Chemical Society and Tetrahedron: Asymmetry, detailing the methodology and applications of the Evans Aldol Reaction.