Enantioselective Total Synthesis of (+)-Hinckdentine A via a Catalytic Dearomatization Approach

Optically
pure hinckdentine A was synthesized on a 300 mg scale via an asymmetric
catalysis-based strategy. The key steps to the first asymmetric synthesis
involved (i) enantioselective dearomative cyclization of an achiral N-acyl indole that allowed for the efficient construction
of the key polycyclic indoline intermediate with a crucial tetrasubstituted
stereogenic carbon center, (ii) Beckmann fragmentation-mediated ring
expansion, (iii) rearrangement-based introduction of an anilinic nitrogen
atom, (iv) regioselective tribromination, and (v) final closure of
the cyclic amidine moiety.