Catalytic Enantioselective Synthesis of a cis-β-Boronyl Cyclobutylcarboxyester Scaffold and Its Highly Diastereoselective Nickel/Photoredox Dual-Catalyzed Csp3–Csp2 Cross-Coupling to Access Elusive trans-β-Aryl/Heteroaryl Cyclobutylcarboxyesters

作者：Kévin Nguyen, Helen A. Clement, Louise Bernier, Jotham W. Coe, William Farrell, Christopher J. Helal, Matthew R. Reese, Neal W. Sach, Jack C. Lee, Dennis G. Hall · 发表于：ACS Catalysis · 年份：2020 · DOI：10.1021/acscatal.0c04520 · 被引用次数：46 · 研究领域：Organoboron and organosilicon chemistry、Radical Photochemical Reactions、Catalytic C–H Functionalization Methods

Chiral cyclobutanes are components of numerous bioactive natural products, and consequently, they have also gained significant attention in medicinal chemistry. Optically enriched cyclobutylboronates can serve as valuable synthetic intermediates for the synthesis of a broad variety of chiral cyclobutanes through exploiting the versatility of the boronyl functionality. Herein, by using a high-throughput ligand screening approach, an efficient method for the asymmetric conjugate borylation of a cyclobutene 1-carboxyester was optimized, leading to a highly enantioenriched cis -β-boronyl cyclobutylcarboxyester scaffold (99% ee, >20:1 dr). Of the 118 ligands screened, the Naud family of phosphine–oxazoline ligands was found to be the most effective. Computational modeling of the possible preinsertion complexes shows a large preference for the π-bound Cu(I)–alkene complex where the substrate’s large benzhydryl ester occupies a relatively unhindered quadrant of the chiral ligand in a spatially tight environment that is highly specific for the cyclobutenoate substrate and imparts much lower selectivity with larger ring substrates. The cis diastereoselectivity is proposed to arise from a sterically controlled, irreversible protodecupration step. A highly diastereoselective nickel/photoredox dual-catalyzed Csp 3 –Csp 2 cross-coupling of the corresponding trifluoroborate salt with aryl/heteroaryl bromides and cycloalkenyl nonaflates was developed, providing access to a wide diversity of...