Asymmetric construction of a quaternary carbon center by tandem (4 + 2)/(3 + 2) cycloaddition of a nitroalkene. The total synthesis of (-)-mesembrine

The seven-step synthesis of enantiomerically pure (-)-mesembrine from 2,2-disubstituted 1-nitroalkene is described. The key step in the synthesis is the tandem inter (4 + 2)/intra (3 + 2) cycloaddition of a 2,2-disubstituted alkene and a chiral vinyl ether derived from (1R,2S)-2-(1-methyl-1-phenylethyl)cyclohexanol to form the octahydroindole framework of the target compound. The conditions and mechanisms for the reactions are presented.