Phosphine-Catalyzed Regio- and Stereoselective Umpolung Addition of Amides to Alkynoates: Access to Complex α,β-Dehydroamino Acid Derivatives

Abstract

Accessing complex α,β-dehydroamino acids remains challenging due to the instability of the enamine product during N-terminal deprotection. We report a mild, organocatalytic method for the installation of primary amides on the α-carbon of alkynoates that avoids N-terminal deprotection. The PBu3 catalyst is key to umpolung reactivity and affords α,β-dehydroamino acids in good yield with excellent (Z)-selectivity. The utility of this reaction was demonstrated in the synthesis of two natural products: a 2,5-diketopiperazine and scutianene M.