Stereoselective Synthesis of γ-hydroxy-α-amino acids via intramolecular amidomercuration

Abstract

A general method for the stereoselective conversion of homoallylic alcohols to erythro- or threo-β-hydroxy-α-amino acids is described. The key step is the stereoselective mercuric ion-initiated cyclofunctionalization of acylaminomethyl ether derivatives of the homoallylic alcohols (3 → 8). The stereochemistry of the products obtained from the cyclofunctionalization is controlled by the choice of reaction conditions. Reaction under conditions of kinetic control leads to predominant formation of cis 4,6-disubstituted tetrahydro-1,3-oxazines, while reaction under conditions which allow for equilibration of the organomercurial intermediates results in the formation of the trans stereoisomer with very high stereoselectivity. Oxidative demercuration and oxidation of the resulting alcohol produces a protected form of the title amino acids (8 → 9 → 10). Cleavage of the tetrahydrooxazine ring with hydrobromic acid then produces the amino acid products asγ-butyrolactone hydrobromides ( 11 and 12). This general method thus allows for stereoselective synthesis of either diastereomer of the amino acid product starting with a single homoallylic alcohol.