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

## TL;DR

A new metal-free method for modifying amino acids at the N-terminal is developed using radical cyclization to create functionalized succinimide derivatives.

## Contribution

A metal-free strategy for selective N-terminal cyclization of amino acids using radical cascade cyclization with sulfonyl hydrazides.

## Key findings

- The method allows efficient synthesis of functionalized succinimide derivatives with good E/Z ratios and moderate to good yields.
- The product was successfully used in Suzuki coupling and dipeptide formation reactions.

## 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.

NIS/H2O2-mediated metal-free radical cascade cyclization of amino acid-tethered 1,6-enynones with sulfonyl hydrazide has been developed for selective N-terminal cyclization of amino acids by producing highly functionalized succinimide derivatives.