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

The design and development of supporting ligands have\nsignificantly\npropelled the discovery of new catalytic reactions and the improvement\nof existing ones. Among these, axially chiral biphenols and 1,1′-binaphthalene-2,2′-diol\n(BINOL) are some of the most privileged ligands used in a wide array\nof enantioselective reactions. Despite the well-established benefits\nof structural modifications to biphenol and BINOL scaffolds, particularly\nat their 3,3′-positionsfor enhancing reactivity and\nstereofidelity in catalytic asymmetric transformationsonly\na limited number of 3,3′-bis-functionalized biphenols and BINOLs\nare currently available. Here, we report a unified strategy to rapidly\naccess a range of axially chiral 3-monosilyl and 3,3′ bis-silyl-substituted\nand biphenols and BINOLs as well as their corresponding 3-monosilyl\nand 3,3′ bis-silyl BINOL-based phosphoramidites. This approach\ninvolves traceless acetal-directed, catalytic two-fold C–H\nsilylation of axially chiral biaryls, coupled with selective monoprotodesilylation,\nexpanding the versatility of catalytic C–H functionalization\nin ligand design and development. Scope studies on the augmentation\nof the topological space of potentially stereoselectivity-amplifying\n3,3′-bis-silyl substituents in axially chiral biphenols and\nBINOLs were achieved through C–H silylation of biphenols and\nBINOLs using various dihydrosilanes, as well as the derivatization\nof 3,3′-silanes, leading to functionalized silane-substituted\nbiphenols and BINOLs. Lastly, the phosphoramidation of newly synthesized\n3-monosilyl and 3,3′ bis-silyl BINOL and biphenols with dichlorophosphinamine\nprovided a series of 3-monosilyl and 3,3′ bis-silyl BINOL-based\nphosphoramidites. The efficiency of this synthetic approach is underscored\nby its short synthetic steps, expedited reaction times, and minimal\npurification, making it versatile for the synthesis of a wide array\nof organosilicon-functionalized axially chiral biaryls and phosphoramidites.