Radical Cyclization of Ynamides to Nitrogen Heterocycles

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 stereo- selective manner, to the corresponding 2-arylidene-pyrrolidines 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.

Controllable Synthesis of Cyclopenta[b]indolines via Photocatalytic Fluoroalkylative Radical Cyclization Cascade of Ynamides

“…Ynamides have long been recognized as readily accessible, reactive, and versatile building blocks in the construction of intricate molecular architectures . In recent years, the radical cyclization of ynamides has emerged as an appealing approach for the construction of diverse N -heterocyclic frameworks of biological and pharmaceutical significance . Pursuing our continuous research interests in 5- endo cyclization, we envisioned that fluoroalkylated cyclopenta­[ b ]­indolines might be constructed from N -aryl ynamides via a fluoroalkylative 5- endo cyclization and subsequent trapping of the resulting cyclopentyl radical by an intramolecular aryl ring (Scheme c).…”