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.