Total Synthesis of Penicibilaenes via C–C Activation-Enabled Skeleton Deconstruction and Desaturation Relay-Mediated C–H Functionalization

Herein, we describe the first total synthesis of sesquiterpene penicibilaenes A and B through a "C–C/C–H" approach. In the "C–C" stage, the Rh-catalyzed "cut-and-sew" transformation between trisubstituted alkene and cyclobutanone has been employed to construct the unique tricyclo[6.3.1.01,5]dodecane skeleton and the all-carbon quaternary center. Critical linker and Lewis acid effects have been identified for the C–C activation process. In the "C–H" stage, a desaturation relay-based strategy involving consecutive ketone α,β-dehydrogenation and β-functionalization has been adopted to introduce the 1,3,5-triad stereocenters to the core. The synthesis of penicibilaenes A and B has been completed in 13 and 14 steps, respectively, in the longest linear sequence.