Synthesis of α,α-disubstituted unnatural amino acid derivatives using the aza-[2,3]-Wittig sigmatropic rearrangement

Abstract

Aza-[2,3]-Wittig rearrangement precursors derived from alanine, valine, phenylalanine and phenylglycine were synthesised with diethylamide and methylester anion stabilising groups. In the amide series only the alanine derived precursor rearranged upon deprotonation with KH. In the ester series the alanine, valine and phenylalanine precursors rearranged successfully with KH. The phenylalanine ester precursor gave an unselective rearrangement whereas rearrangement of the alanine and valine ester precursors gave levels and sense of diastereoselectivity in line with our transition state model. The products are chiral α,α-disubstituted-α-amino acid derivatives possessing two adjacent stereocentres and a vinyl silane synthetic handle.