Ni/Photoredox-Catalyzed Enantioselective Cross-Electrophile Coupling of Styrene Oxides with Aryl Iodides

Abstract

A Ni/photoredox-catalyzed enantioselective reductive coupling of styrene oxides and aryl iodides is reported. This reaction affords access to enantioenriched 2,2-diarylalcohols from racemic epoxides via a stereoconvergent mechanism. Multivariate linear regression (MVLR) analysis with 29 bioxazoline (BiOx) and biimidazoline (BiIm) ligands revealed that enantioselectivity correlates with electronic properties of the ligands, with more electron-donating ligands affording higher ee's. Experimental and computational mechanistic studies were conducted, lending support to the hypothesis that reductive elimination is enantiodetermining and the electronic character of the ligands influences the enantioselectivity by altering the position of the transition state structure along the reaction coordinate. This study demonstrates the benefits of utilizing statistical modeling as a platform for mechanistic understanding and provides new insight into an emerging class of chiral ligands for stereoconvergent Ni and Ni/photoredox cross-coupling.

Auto-QChem: an automated workflow for the generation and storage of DFT calculations for organic molecules

“…In another example, we developed a Ni/photoredox-catalyzed enantioselective cross-electrophile coupling of aryl iodides and styrene oxides. 39 The optimal ligand, a chiral biimidazoline (BiIm) ligand, was discovered only after extensive screening of common chiral amine bidentate ligands. Bioxazoline (BiOx) ligands previously used in our asymmetric reductive coupling of aziridines 40 resulted in good enantioselectivity but low to moderate yield of the product.…”

Recent Progress on Transition-Metal-Mediated Reductive C(sp3)–O Bond Radical Addition and Coupling Reactions

“…The same group has further utilized a chiral bisimidazoline (BiIm) ligand for asymmetric epoxide radical ring opening/arylation to afford 2-hydroxyl biaryl ethane products in high level of enantioselectivities (Scheme 3b). 11 The authors analyzed the results of bisoxazoline (BiOx) and bisimidazoline (BiIm) ligands using statistical modeling to identify the structure-selectivity relationship, wherein higher ee's correlates with better electron-donating ligands.…”

Mechanistic Inference from Statistical Models at Different Data-Size Regimes

“…Moreover, a recent review by Norrby and co-workers provides an excellent computational chemistry assessment of how the mechanistic study of organic reactivity has been affected by machine learning . Herein, we also set mechanistic inference as our mainstay; however, our specific aim is to demonstrate through selected examples that a careful experimental design not only enables efficient reaction optimization but can concurrently generate uniquely suitable data sets for mechanistic investigation. − …”