2026/05/01 by Eli Jones, Robert T. Martin, David W. C. MacMillan · 1 voice
Chemistry · #Asymmetric Synthesis and Catalysis #Catalytic Cross-Coupling Reactions #Synthetic Organic Chemistry Methods
paper · doi:10.26434/chemrxiv.15002635/v1
openalex publication_date 2026/05/01 · openalex created_date 2026/05/05 · openalex updated_date 2026/07/14
Multi-substituted alkenes are valuable structural motifs that also serve as key intermediates in complexity-building transformations; however, their stereoselective synthesis remains a longstanding challenge. Vinyl 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 vinyl bromides with alcohols, providing a direct, modular approach to multi-substituted alkenes. This transformation exhibits broad substrate scope across both alcohol and vinyl bromide partners, delivering over 30 multi-substituted alkenes. Moreover, we developed a complementary stereoselective bromovinylation from readily synthesized gem -dibromoolefins to address the limited availability of stereodefined vinyl bromides. In the presence of a phthalimide additive, selective monofunctionalization enables access to over 40 stereodefined vinyl bromides, providing a general and stereoselective pathway to these otherwise difficult-to-access intermediates. Direct access to vinyl bromides enables piecewise stereoselective assembly of multi-substituted 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.