The development and application of enantioselective reactions of masked acyl cyanide reagents

Masked acyl cyanide (MAC) reagents are shown to be effective umpolung synthons for enantioselective additions to electrophiles. The reactions are catalyzed by chiral bifunctional catalysts and afford adducts in high yields and with excellent enantioselectivities. The addition products are unmasked to produce dicyanohydrins that, upon treatment with a variety of nucleophiles, provides access to ?-ketocarboxylic acid derivatives or ?-amino acid derivatives. The use of this umpolung synthon has enabled, in enantiomerically enriched form, the first total synthesis of the prenylated phenol (+)-fornicin C. Notably, the methodology also provides an alternative method for peptide bond formation.