Desymmetric sulfonylation of prochiral siladiols and related tandem sequences to multifunctional Si-chiral platform molecules

Organosilanes are not found in nature but play a crucial role in the sustainable development of modern society. Si-chiral organosilanes represent a type of novel chemical space that is highly desirable for research oriented in terms of their properties, including synthetic chemistry, drug discovery, and materials and life sciences. While much effort has been given to the catalytic enantioselective construction of Si-chirality, the facile synthesis of multifunctional Si-chiral silanes remains undeveloped. Here, we report an unprecedented highly enantioselective copper-catalyzed desymmetric sulfonylation or acylation of prochiral 1,3-siladiols for the expedient synthesis of multifunctional Si-chiral silanes with both a hydroxymethyl group and an ester group as synthetic handles. A one-pot tandem desymmetric sulfonylation/substitution sequence, internally reusing waste chloride or bromide formed from the upstream sulfonylation step as the reagent for a substitution step, is also exploited for the atom-efficient synthesis of Si-chiral silylmethanols featuring a chloromethyl or bromomethyl group. A newly developed sterically confined pyridine-bis(oxazoline) (PYBOX) ligand with a bulky C4 amide-containing shielding group is crucial for achieving excellent reactivity and enantioselectivity. The scale-up synthesis and various diversifying elaborations of multifunctional Si-chiral silylmethanols further highlight the synthetic practicability of this protocol.