Synthesis of α-Amino Acid Derivatives and Peptides via Enantios

Synthesis of α-Amino Acid Derivatives and Peptides via Enantioselective Addition of Masked Acyl Cyanides to Imines

Kin S. Yang and Viresh H. Rawal, J. Am. Chem. Soc., Article ASAP DOI: 10.1021/ja510135t  Publication Date (Web): November 4, 2014                     Copyright © 2014 American Chemical Society

A general, asymmetric synthesis of amino acid derivatives is reported. Masked acyl cyanide (MAC) reagents are shown to be effective umpolung synthons for enantioselective additions to N-Boc-aldimines. The reactions are catalyzed by a modified cinchona alkaloid, which can function as a bifunctional, hydrogen bonding catalyst, and afford adducts in excellent yields (90–98%) and high enantioselectivities (up to 97.5:2.5 er). Unmasking the addition products gives acyl cyanide intermediates that are intercepted by a variety of nucleophiles to afford α-amino acid derivatives. Notably, the methodology provides an alternative method for peptide bond formation.