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Copper-Catalyzed Radical C–C Bond Cleavage and [4+1] Annulation Cascade of Cycloketone Oxime Esters with Enaminothiones

He, Yuan, Lou, Jiang, Wu, Kaikai, Wang, Hongmei, Yu, Zhengkun
Journal of organic chemistry 2019 v.84 no.4 pp. 2178-2190
catalytic activity, chemical bonding, chemical reactions, chemical structure, cleavage (chemistry), copper, esters, organic chemistry, regioselectivity, thermodynamics
Carbon–carbon bond formation is among the most important reactions in organic synthesis. Reconstruction of a carbon–carbon bond through ring-opening C–C bond cleavage of a strained carbocycle usually occurs via a thermodynamically preferable pathway. However, carbon–carbon bond formation through thermodynamically less favorable C–C bond cleavage has seldom been documented. Herein, we disclose an unusual C–C bond cleavage of cycloketone oxime esters for [4+1] annulation. Under anaerobic copper(I) catalysis, cycloketone oxime esters underwent regioselective, thermodynamically less favorable radical C–C bond cleavage followed by annulation with enaminothiones; that is, α-thioxo ketene N,S-acetals efficiently affording 2-cyanoalkyl-aminothiophene derivatives. Cyclobutanone, -pentanone, -hexanone, and -heptanone oxime esters could act as the effective C1 building blocks in the annulation reaction. An iminyl radical mechanism is proposed for the rare C–C bond cleavage/[4+1] annulation cascade.