Piecewise Stereoselective Assembly of Multisubstituted Alkenes

Multisubstituted alkenes are valuable structural motifs that also serve as key intermediates in complexity-building transformations; however, their stereoselective synthesis remains a longstanding challenge. Alkenyl bromides are appealing coupling handles for alkene synthesis, though their application would be greatly enhanced if they could be coupled directly with alkyl radicals derived from feedstock alcohols. Herein, we report a nickel metallaphotoredox-enabled deoxygenative cross-coupling of alkenyl bromides with alcohols, providing a direct, modular approach to multisubstituted alkenes. This transformation exhibits a broad substrate scope across both alcohol and alkenyl bromide partners, delivering over 30 multisubstituted alkenes. Moreover, we developed a complementary stereoselective bromoalkenylation from readily synthesized gem-dibromoolefins to address the limited availability of stereodefined alkenyl bromides. In the presence of a phthalimide additive, selective monofunctionalization enables access to over 40 stereodefined alkenyl bromides, providing a general and stereoselective pathway to these otherwise difficult-to-access intermediates. Direct access to alkenyl bromides enables piecewise stereoselective assembly of multisubstituted alkenes through sequential alcohol coupling or stereoretentive Suzuki–Miyaura reactions. These strategies are illustrated via iterative cross-coupling sequences and the total synthesis of (+)-sponalisolide B.