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 nudeophiles to afford alpha-amino acid derivatives. Notably, the methodology provides an alternative method for peptide bond formation.

 

 

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 136:46 (19 Nov. 2014): 16148-51