Asymmetric total synthesis of benzenoid cephalotane-type diterpenoids through a cascade C(sp) & C(sp)-H activation.

Cephalotane diterpenoids, featuring unique and complicated carbon skeletons and remarkable antitumor activities from the Cephalotaxus genus, have been gaining increasing attention. Herein, we report the asymmetric and divergent total synthesis of benzenoid cephalotane-type diterpenoids containing the identical 6/6/6/5 tetracyclic and the bridged δ-lactone skeleton with different oxidation states. A cascade of C(sp) and C(sp)-H activation has been developed to efficiently prepare the characteristic and synthetically challenging 6/6/6/5 tetracyclic skeleton through a pivotal palladium/NBE-cocatalyzed process. The feature of this strategy is the construction of three C-C bonds (two C(sp)-C(sp) bonds and one C(sp)-C(sp) bond) and the formation of two cycles with two chiral centers in a single step. The application of this method for the rapid assembly of the skeleton of benzenoid cephalotane-type diterpenoids is demonstrated through the concise and asymmetric total synthesis of cephanolides A-D (1-4) and ceforalide B (5) via late-stage modification.