Radical Cyclization of Ynamides to Nitrogen Heterocycles

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 degrees 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.

Automated summary

An efficient radical cyclization of suitably functionalized ynamides to nitrogen-containing heterocycles is reported. The reaction shows high regio- and stereoselectivity, leading to good to excellent yields. Additionally, the exocyclic double bond can be used for further chemical diversification, and the generality of this radical cyclization is demonstrated by its extension to the synthesis of other nitrogen heterocycles.