Iridium-Catalyzed Asymmetric Difunctionalization of C–C σ-Bonds Enabled by Ring-Strained Boronate Complexes
Hong‐Cheng Shen, Mihai V. Popescu, Ze‐Shu Wang, Louis de Lescure, Adam Noble, Robert S. Paton, Varinder K. Aggarwal
Abstract
High Resolution Image Download MS PowerPoint Slide Enantioenriched organoboron intermediates are important building blocks in organic synthesis and drug discovery. Recently, transition metal-catalyzed enantioselective 1,2-metalate rearrangements of alkenylboronates have emerged as an attractive protocol to access these valuable reagents by installing two different carbon fragments across C═C π-bonds. Herein, we report the development of an iridium-catalyzed asymmetric allylation-induced 1,2-metalate rearrangement of bicyclo[1.1.0]butyl (BCB) boronate complexes enabled by strain release, which allows asymmetric difunctionalization of C–C σ-bonds, including dicarbonation and carboboration. This protocol provides a variety of enantioenriched three-dimensional 1,1,3-trisubstituted cyclobutane products bearing a boronic ester that can be readily derivatized. Notably, the reaction gives trans diastereoisomers that result from an anti -addition across the C–C σ-bond, which is in contrast to the syn -additions observed for reactions promoted by Pd II –aryl complexes and other electrophiles in our previous works. The diastereoselectivity has been rationalized based on a combination of experimental data and density functional theory calculations, which suggest that the BCB boronate complexes are highly nucleophilic and react via early transition states with low activation barriers.