Total Synthesis of (−)-Himalensine A

The
first enantioselective synthesis of (−)-himalensine
A has been achieved in 22 steps. The synthesis was enabled by a novel
catalytic, enantioselective prototropic shift/furan Diels–Alder
(IMDAF) cascade to construct the ACD tricyclic core. A reductive radical
cyclization cascade was utilized to build the B ring, and end-game
manipulations featuring a molecular oxygen mediated γ-CH oxidation,
a Stetter cyclization to access the pendant cyclopentenone, and a
highly chemoselective lactam reduction delivered the natural product
target.