Lewis Base‐Catalyzed Enantioselective O‐Boc Protection Enables Access to Silicon‐Stereogenic Organosilanes

Comprehensive Summary The integration of protection chemistry with desymmetrization or kinetic resolution has emerged as a powerful tool for the construction of optically active compounds. Over the past two decades, a variety of enantioselective silyl protection methodologies have been established through transition‐metal catalysis, organocatalysis, and enzymatic catalysis. To further expand the scope of enantioselective protection strategies, our group recently proposed a Lewis base‐catalyzed enantioselective Boc protection approach using readily available di‐ tert ‐butyl dicarbonate (Boc 2 O). Based on this concept, we have developed isothiourea‐ and biscinchona alkaloid‐catalyzed atroposelective O‐Boc protection reactions for the synthesis of axially chiral compounds. Meanwhile, organosilicon compounds featuring a stereogenic silicon center have drawn considerable attention due to their promising applications as chiral reagents, pharmaceuticals, and functional materials. However, in the field of enantioselective protection chemistry, only a few O ‐silyl protection strategies have been reported to access silicon‐stereogenic silanols. Herein, as a continuation of our efforts to extend enantioselective Boc protection to other forms of chirality, we report a biscinchona alkaloid‐catalyzed enantioselective O‐Boc protection protocol for the preparation of silicon‐stereogenic organosilanes. In the presence of a commercially available Lewis base catalyst, two identical phenolic groups tethered to a silicon center are effectively discriminated to react with Boc 2 O, delivering enantioenriched organosilanes bearing a silicon stereocenter in good to excellent yields with high enantioselectivities. This desymmetrization process is readily scalable to gram quantities without significant loss of efficiency. Combined with the low cost and easy availability of the catalyst and reagent, this method offers a practical approach to silicon‐stereogenic molecules. Furthermore, the resulting products can be conveniently transformed into silicon‐stereogenic phosphines through downstream derivatizations, and preliminary studies indicate their potential application as chiral ligands in Pd‐catalyzed asymmetric allylic alkylation of diethyl malonate.