Dehydration of Chiral α-Amides to Chiral α-Nitriles Under the Appel Reaction Conditions

Abstract

An efficient synthesis of Nα-protected amino nitriles from Nα-protected amino acid amides employing Ph3P, I2 and NMM was described. Various amino acid amides, protected by Fmoc, Z and Boc were conveniently converted to nitriles in high yields. Side chain protected amino acid amides were well-tolerated and a good yield of products was obtained. The protocol serves as one of the mild, among a few available, methods for the racemization-free conversion of Nα-protected amino acid amides to corresponding nitriles with neither harsh condition nor catalyst. Nα-protected amino acid amides were efficiently transformed to Nα-protected amino acid nitriles employing I2, PPh3, and NMM under mild reaction conditions. Fmoc, Boc and Cbz-protected amino acid amides were converted into their corresponding nitriles groups. Side chain protected amino acid amides also underwent facile conversion to their corresponding nitriles with good yields.