Radical Cyclization of Ynamides to Nitrogen Heterocycles

Dedicated to Prof. Alain Krief on the occasion of his 80^th birthday

Abstract

An efficient radical cyclization of suitably functionalized ynamides to nitrogen-containing heterocycles is reported. Upon reaction with tributyltin hydride in the presence of catalytic amounts of AIBN in toluene at 80 °C, a range of ynamides bearing a N-iodopropyl chain could be smoothly cyclized, in a highly regio- and stereoselective manner, to the corresponding 2-arylidenepyrrolidines in good to excellent yields. The exocyclic double bond was in addition shown to be an excellent anchor for further chemical diversification and the generality of this radical cyclization could be highlighted by its extension to the synthesis of other nitrogen heterocycles including piperidines, azepanes, pyrazolidines and hexahydropyridazines.

Key words

ynamides - radical cyclization - pyrrolidines - heterocycles - ring closure

Publication History

Received: 04 May 2022

Accepted after revision: 03 June 2022

Accepted Manuscript online:
03 June 2022

Article published online:
12 July 2022

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