Enantioselective approach to quinolizidines: total synthesis of cermizine D and formal syntheses of senepodine G and cermizine C.

The formal syntheses of C5-epi-senepodine G and C5-epi-cermizine C have been accomplished through a novel diastereoselective, intramolecular amide Michael addition process. The total synthesis of cermizine D has been achieved through use of an organocatalyzed, heteroatom Michael addition to access a common intermediate. Additional key steps of this sequence include a matched, diastereoselective alkylation with an iodomethylphenyl sulfide and sulfone-aldehyde coupling/reductive desulfurization sequence to combine the major subunits. The utility of a Hartwig-style C-N coupling has been explored on functionally dense coupling partners. Diastereoselective conjugate additions to α,β-unsaturated sulfones have been investigated, which provided the key sulfone intermediate in just six steps from commercially available starting materials. The formal syntheses of senepodine G and cermizine C have been accomplished through an intramolecular cyclization process of a N-Boc-protected piperidine sulfone.