Enantioselective palladium-catalyzed carbonylation of gem-dibromoalkenes to chiral benzo[7]annulenes

Chemo- and enantioselective mono-debrominative functionalization of 2,2-disubstituted 1,1-dibromoalkenes to access tetrasubstituted vinyl bromides remains a formidable challenge, owing to competitive double functionalization and the difficulty in achieving enantiocontrol when the gem-dibromoalkenyl moiety embodies a prochiral plane. Herein, we report a palladium-catalyzed asymmetric monocarbonylation of conformationally rigid, prochiral benzo[7]annulene-based gem-dibromoalkenes, furnishing inherently chiral tetrasubstituted benzo[7]annulene derivatives with excellent yields (up to 97%) and high enantioselectivities (up to 98:2 er). Notably, the inclusion of simple acid additives enables a switchable pathway divergence to double debrominative carbonylation, delivering inherently chiral trisubstituted vinyl carboxylic acids with equally good chemo- and enantiocontrol. This protocol is also applicable to unsymmetric gem-dibromoalkene substrates, affording the corresponding products with synthetically useful yields and enantioselectivities. Mechanistic studies, supported by DFT calculations, reveal that the acid-induced formation of a key alkylidene carbene–Pd–H species is pivotal for the pathway switch, followed by enantioselective carbene insertion into the Pd–H bond and subsequent CO insertion. This work not only provides a modular and divergent route to both tri- and tetrasubstituted inherently chiral benzo[7]annulene scaffolds, but also represents the first asymmetric desymmetrization of planarly prochiral gem-dibromoalkenes via palladium catalysis. The authors report a palladium-catalyzed asymmetric monocarbonylation of conformationally rigid, prochiral benzo[7]annulenebased gemdibromoalkenes, furnishing inherently chiral tetrasubstituted benzo[7]annulene derivatives with excellent yields and high enantioselectivities.