Total Synthesis of Caesalpinnone A and Caesalpinflavan B: Evolution of a Concise Strategy

The total syntheses
of caesalpinnone A (1) and its
putative biosynthetic precursor caesalpinflavan B (3)
are described. Herein, we describe the evolution of a synthetic strategy
toward 1 and 3, which entails a convergent
Barluenga coupling that quickly delivers a heavily functionalized
benzopyran containing the core carbon framework and exploration of
two distinct synthetic routes for forging the flavanoid C-ring by
reducing a sterically encumbered embedded alkene: one via a stepwise
approach and a second, more direct and atom-economical, enabled by
a Shenvi-HAT hydrogenation. The latter strategy allowed access to
caesalpinflavan B in 6 steps after Pd-mediated deallylation. A late-stage
dearomative phenolic oxidation and deallylation/oxa-Michael cascade
was implemented to access caesalpinnone A (1) in 7 steps.
We also describe an enantioselective total synthesis and stereochemical
revision of (−)-caesalpinflavan B, as well as a formal enantioselective
synthesis of (−)-caesalpinnone A, by implementing an enantioselective
Pd-catalyzed conjugate addition developed by Stoltz.