Concise and Modular Access to a Chiral Biaryl Monophosphine Library and Downstream Use in Catalytic Enantioselective Transformations.

Abstract

Atropoisomeric biaryl monophosphines, chiral variants of Buchwald-type ligands, are powerful ligands for asymmetric catalysis. However, their synthesis relies heavily on resolution or step-intensive synthetic approaches, restricting structural diversity and tuning options, thus limiting systematic exploration of their catalytic potential. We report a unified strategy for streamlined access to a broadly tunable family of atrop-chiral biaryl monophosphines. The three-step assembly protocol first exploits a CpX-IrIII-catalyzed atroposelective C─H arylation of phosphine oxide to forge the biaryl core with three different diversity points. Subsequently, reduction to the phosphine and installation of the fourth diversity point provide a diverse library of 35 chiral air-stable monophosphine ligands. Their catalytic performance was benchmarked in a challenging enantioselective gold-catalyzed cycloisomerization and a palladium-catalyzed asymmetric phenol dearomatization, leading to the discovery of high-performing library members providing excellent enantioselectivities of up to 99:1 er in both transformations.

Abstract as supplied by the indexing source. © the authors / publisher.