Achiral sulfur functional groups, such as sulfonamide, sulfone, thiol and thioether, are common in drugs and natural products. By contrast, chiral sulfur functional groups are often neglected as pharmacophores 1 – 3 , although sulfoximine, with its unique physicochemical and pharmacokinetic properties 4 , 5 , has been recently incorporated into several clinical candidates. Thus, other sulfur stereogenic centres, such as sulfinate ester, sulfinamide, sulfonimidate ester and sulfonimidamide, have started to attract attention. The diversity and complexity of these sulfur stereogenic centres have the potential to expand the chemical space for drug discovery 6 – 10 . However, the installation of these structures enantioselectively into drug molecules is highly challenging. Here we report straightforward access to enantioenriched sulfinate esters via asymmetric condensation of prochiral sulfinates and alcohols using pentanidium as an organocatalyst. We successfully coupled a wide range of sulfinates and bioactive alcohols stereoselectively. The initial sulfinates can be prepared from existing sulfone and sulfonamide drugs, and the resulting sulfinate esters are versatile for transformations to diverse chiral sulfur pharmacophores. Through late-stage diversification 11 , 12 of celecoxib and other drug derivatives, we demonstrate the viability of this unified approach towards sulfur stereogenic centres.

Silicon hydrides, alkynylsilanes, and alkoxylsilanes were activated by fluoride in the presence of bisguanidinium catalyst to form hypervalent silicate ion pairs. These activated silicates undergo 1,4-additions with chromones, coumarins, and α-cyanocinnamic esters generating enolsilicate intermediates, for a consequent stereoselective alkylation reaction. The reduction-alkylation reaction proceeded under mild conditions using polymethylhydrosiloxane, a cheap and environmentally friendly hydride source. The addition-alkylation reactions with alkynylsilanes and alkoxylsilanes resulted in the construction of two vicinal chiral carbon centers with excellent enantioselectivities and diastereoselectivities (up to 99% ee, >99:1 dr). Density functional theory calculations and experimental NMR studies revealed that penta-coordinated silicates are crucial intermediates.