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.