Radical cascade cyclization of amino acid-tethered 1,6-enynones with sulfonyl hydrazides for N-terminal modification: synthesis of functionalized succinimide derivatives

Abstract

A metal-free strategy for the N-terminal cyclization of amino acids has been developed by synthesizing highly functionalized succinimide derivatives through radical cyclization of amino acid-tethered 1,6-enynones with sulfonyl hydrazide using NIS and H₂O₂ as an oxidant. The notable advantages of this work includes time-efficient, good E/Z ratio, moderate to good yields, and was synthesized on a gram-scale. Furthermore, the synthetic utility of the product 5aa was performed by (i) Suzuki coupling reaction with iodo-functionality; and (ii) dipeptide formation using glycine methyl ester.