Divergent Synthesis of 1,2,3,4‐Tetrasubstituted Cyclobutenes from a Common Scaffold: Enantioselective Desymmetrization via Dual‐Catalyzed Photoredox Cross‐Coupling

Four‐membered carbocycles are important structural motifs found in several natural products and drugs. Amongst those, cyclobutenes are attractive intermediates because the residual olefin can be manipulated selectively into numerous saturated and unsaturated analogs. Few methods exist to access chiral tri‐ and tetra‐C‐substituted cyclobutenes and they are generally limited in terms of diversification. Herein, a divergent synthetic strategy was developed where a single optically enriched scaffold is diversified into a variety of derivatives with different substitution patterns. To this end, the enantioselective desymmetrization of prochiral 1,2‐dibromocyclobutene imides was enabled by a dual Ir/Ni‐catalyzed photoredox C(sp2)–C(sp3) cross‐coupling with an alkyltrifluoroborate salt to install a convertible carbon fragment in good yields and >90% enantiomeric excess. Exceptional mono‐coupling selectivity is observed and the resulting chiral bromocyclobutene serves as a common scaffold that can be transformed in a divergent manner into several valuable 1,2,3,4‐tetra‐C‐substituted cyclobutane products while maintaining optical purity.