Evans Aldol Reaction

The Evans aldol reaction is one of the various aldol reactions and gives α-alkyl-β-hydroxy carbonyl compounds from carbonyl compounds with an asymmetric auxiliary in high stereoselectivity and high enantiomeric excess. When the carbonyl compound is treated with an organic base and a borane compound as a Lewis acid, the Z-enolate is generated in situ. After that, the borane compound affords the corresponding compound by the addition of an aldehyde via a six-membered transition state. It is considered that the stereochemistry of the product is fixed by the following effects: 1,3-diaxial interaction; steric hindrance of the asymmetric auxiliary; minimization of the dipole interaction between the two carbonyl groups. The Evans aldol reaction is used in total syntheses of natural compounds as a very reliable reaction for many reasons, e.g., two asymmetric carbons can be installed and the stereochemistry of the product can be easily predicted. After the reaction, the remaining chiral auxiliary can be removed by hydrolysis, reduction or transformation of the Weinreb amide. Furthermore, all of the stereoisomers can be separately synthesized by adjusting chiral auxiliaries and Lewis acids.