Anti‐Selective Aldol Reactions of Amino Acid Ester Enolates. Application to the Synthesis of α‐Alkylated β‐Hydroxy Amino Acids

Abstract

AbstractDeprotonation of N‐protected esters of the amino acids alanine 1, ethylglycin 6, valine 7, and phenylalanine 8 with LDA and subsequent addition of various metal salts result in the formation of a probably chelated metal enolate. Aldol reactions of these enolates with aldehydes afford the anti isomers of α‐alkylated α‐amino‐β‐hydroxy acids in a highly diastereoselective fashion. Best results are obtained with titanium enolates, bulky aliphatic aldehydes, and sterically demanding amino acids.