Synthesis of Novel α-Substituted and α,α-Disubstituted Amino Acids by Rearrangement of Ammonium Ylides Generated from Metal Carbenoids

[reaction: see text] A new and general four-step synthesis of protected alpha-substituted and alpha,alpha-disubstituted amino acids has been developed. The key step involves intramolecular ammonium ylide generation from a copper carbenoid with concomitant [2,3] rearrangement. The aromatic template serves as a tether, protecting group, and activating group for peptide coupling. The ylide rearrangement products can be converted into protected cyclic amino acids by ring-closing metathesis.