Rh-Catalyzed Cycloisomerization of 1,8-Enynes Initiated by C–C Activation: Diastereoselective Synthesis of Bicyclo[5.1.0]octene Systems

Transition-metal-catalyzed cycloisomerization of 1,n-enynes has been recognized as a powerful tool for constructing cyclopropane-fused bicycles and polycycles. However, this strategy primarily leads to the synthesis of bicyclo[3.1.0]hexene and bicyclo[4.1.0]heptene skeletons, whereas the synthesis of bicyclo[5.1.0]octene scaffolds is underrepresented due to the challenges associated with forming seven-membered rings. Herein, by taking advantage of the substantial energy gained in the strain release of benzocyclobutenols, we realize a general, mild, and efficient Rh-catalyzed cycloisomerization of 1,8-enynes. This methodology provides a chemo- and diastereoselective approach to complex bicyclo[5.1.0]octene derivatives containing three to four contiguous stereocenters. Experimental and computational mechanistic studies indicate that the reaction proceeds through a pathway involving sequential C–C bond activation, 5-exo-dig cyclization, migratory insertion, and intramolecular Michael addition.