An Unconventional trans - exo -Selective Cyclization of Alkyne-Tethered Cyclohexadienones Initiated by Rhodium(III)-Catalyzed C–H Activation via Insertion Relay

Different from the established trans-endo-selective cyclization of alkyne-tethered electrophiles that involve an E/Z isomerization process, herein, the authors present a novel strategy to allow trans-exo -selective arylative cyclization of 1,6-enynes. Through initiation of rhodium(III)-catalyzed C-H activation, a diverse range of N-heterocyclic directing groups, including pyridine, pyrazole, imidazo[1,2-a] pyridine, benzoxazole, benzothiazole, and purine, was feasible for the cascade transformation, exhibiting high efficiency (up to 92% yield), broad substrate scope, and excellent functional group compatibility. Moreover, the modification of natural products and pharmaceutical compounds was also demonstrated to showcase its synthetic utility. Based on density functional theory (DFT) calculations, a key three-membered ring intermediate through the insertion relay, rather than the direct E/Z isomerization of alkenyl rhodium species, controlled the stereochemical outcome for this trans-exo -selective cyclization. The subsequent ring-opening protonation of the more favored rotamer led to exclusive trans-exo-selectivity. [GRAPHICS] .