Expedited Synthesis of Axially Chiral 3-Monosilyl and 3,3′-Bis-silyl Biphenols, Binaphthols, and Phosphoramidites Enabled by Catalytic Two-Fold C–H Silylation with a Traceless Acetal Directing Group

Abstract

The design and development of supporting ligands have significantly propelled the discovery of new catalytic reactions and the improvement of existing ones. Among these, axially chiral biphenols and 1,1′-binaphthalene-2,2′-diol (BINOL) are some of the most privileged ligands used in a wide array of enantioselective reactions. Despite the well-established benefits of structural modifications to biphenol and BINOL scaffolds, particularly at their 3,3′-positions─for enhancing reactivity and stereofidelity in catalytic asymmetric transformations─only a limited number of 3,3′-bis-functionalized biphenols and BINOLs are currently available. Here, we report a unified strategy to rapidly access a range of axially chiral 3-monosilyl and 3,3′ bis-silyl-substituted and biphenols and BINOLs as well as their corresponding 3-monosilyl and 3,3′ bis-silyl BINOL-based phosphoramidites. This approach involves traceless acetal-directed, catalytic two-fold C–H silylation of axially chiral biaryls, coupled with selective monoprotodesilylation, expanding the versatility of catalytic C–H functionalization in ligand design and development. Scope studies on the augmentation of the topological space of potentially stereoselectivity-amplifying 3,3′-bis-silyl substituents in axially chiral biphenols and BINOLs were achieved through C–H silylation of biphenols and BINOLs using various dihydrosilanes, as well as the derivatization of 3,3′-silanes, leading to functionalized silane-substituted biphenols and BINOLs. Lastly, the phosphoramidation of newly synthesized 3-monosilyl and 3,3′ bis-silyl BINOL and biphenols with dichlorophosphinamine provided a series of 3-monosilyl and 3,3′ bis-silyl BINOL-based phosphoramidites. The efficiency of this synthetic approach is underscored by its short synthetic steps, expedited reaction times, and minimal purification, making it versatile for the synthesis of a wide array of organosilicon-functionalized axially chiral biaryls and phosphoramidites.