Eight-Step Enantioselective Total Synthesis of (-)-Cycloclavine.

The first enantioselective total synthesis of (-)-cycloclavine was accomplished in 8 steps and 7.1 % overall yield. Key features include the first catalytic asymmetric cyclopropanation of allene, mediated by the dirhodium catalyst Rh2 (S-TBPTTL)4 , and the enone 1,2-addition of a new TEMPO carbamate methyl carbanion. An intramolecular strain-promoted Diels-Alder methylenecyclopropane (IMDAMC) reaction provided a pivotal tricyclic enone intermediate with more than 99 % ee after crystallization. The synthesis of (-)-1 was completed by a late-stage intramolecular Diels-Alder furan (IMDAF) cycloaddition to install the indole.