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

摘要

An efficient, total synthesis of the Sceletium alkaloid (-)-mesembrine is accomplished in seven steps and 19/100 yield from a functionalized nitroalkene (itself prepared in six steps and 34/100 yield from etyl 3-bromopropionate). The construction of the octahydronindole framework of mesembrine features a tandem inter [4+2]/intra [3+2] cycloaddition of a 2,2-disubstituted 1-nitroalkene and a chiral vinyl ether derived from (1R,2S)-2-(1-methyl-1-phenylethyl)cyclohexanol as the central strategic element.