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

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.