Palladium-Catalyzed Enantioselective Intramolecular Dearomative Heck Reaction

Enantioselective
intramolecular dearomative Heck reactions have
been developed by Pd-catalyzed cross-coupling of aryl halides or aryl
triflates with the internal CC bond of indoles, benzofurans,
pyrroles, and furans. A variety of structurally unique spiroheterocycles
and benzofused heterocycles having N/O-substituted quaternary carbon
stereocenters, and exocyclic olefin moieties were afforded in moderate
to excellent yields with good to excellent enantioselectivities, showing
a broad scope of the present protocol. A series of new BINOL- and
H8-BINOL-based phosphoramidite ligands were synthesized and proved
to be efficient chiral ligands in the reactions of C2-tethered substrates
to form spiroheterocycles. (S)-SEGPHOS turned out
to be a good ligand for the reaction delivering benzofused indolines
and pyrrolines. Synthetic applications based on transformations of
the exocyclic double bonds were realized without loss of enantiopurities,
including hydrogenation, hydroborylation, and stereospecific ring-expanding
rearrangement.