Efficient Synthesis of Sulfur-Stereogenic Sulfoximines via Ru(II)-Catalyzed Enantioselective C–H Functionalization Enabled by Chiral Carboxylic Acid

Abstract

Ru(II)-catalyzed enantioselective C−H functionalization involving an enantiodetermining C−H cleavage step remains undeveloped. Here we describe a Ru(II)-catalyzed enantioselective C−H activation/annulation of sulfoximines with αcarbonyl sulfoxonium ylides using a novel class of chiral binaphthyl monocarboxylic acids as chiral ligands, which can be easily and modularly prepared from 1,1′-binaphthyl-2,2′-dicarboxylic acid. A broad range of sulfur-stereogenic sulfoximines were prepared in high yields with excellent enantioselectivities (up to 99% yield and 99% ee) via desymmetrization, kinetic resolution, and parallel kinetic resolution. Furthermore, the resolution products can be easily transformed to chiral sulfoxides and key intermediates for kinase inhibitors.

Organocatalytic atroposelective construction of axially chiral N, N- and N, S-1,2-azoles through novel ring formation approach

“…To date, the catalytic asymmetric preparation of stereogenic C-C axial chiral aryl-isothiazole S-oxides remains unexplored. Possible methods to address this challenge may involve the formation of axis and stereogenic sulfur center, but the simultaneous control of the stereogenic sulfur center and axis has not been achieved 30 , 51 – 59 . Our current strategy involves the VQMs bearing a racemic sulfinamide moiety, which can be deprotonated to form a carbon electrophile and then undertake an intramolecular S–C bond formation to access axially chiral naphtyl-isothiazole S-oxides through kinetic resolution, and recovering one isomer of sulfinamides 1 as stereogenic sulfur center derivatives.…”

Asymmetric transformations from sulfoxonium ylides

“…Also in 2021, Shi and co-workers reported the first enantioselective C–H insertion/annulation with sulfoxonium ylides ( Scheme 15D ). 142 Using sulfoximines as substrates and sulfoxonium ylides as coupling partners in a chiral ruthenium-complex catalyzed reaction, the authors synthesized 41 enantioenriched cyclic sulfoximines (121) via desymmetrization, kinetic resolution and parallel kinetic resolution strategies. In most cases the enantioselectivity was excellent (up to 98% ee).…”

Synthesis of P- and S-Stereogenic Compounds via Enantioselective C–H Functionalization

“…In 2021, Shi and co-workers reported the first (p-cymene)Ru(II)-catalyzed asymmetric C-H activation enabled by CCA ligands. 48 They successfully achieved the synthesis of sulfur-stereogenic sulfoximines via ruthenium(II)-catalyzed enantioselective C-H functionalization assisted by C 1symmetric binaphthyl monocarboxylic acids L20 and L21 (Scheme 22). 48 This was the first report of a ruthenium(II)catalyzed asymmetric C-H functionalization via an enantiodetermining C-H cleavage step.…”

“…48 They successfully achieved the synthesis of sulfur-stereogenic sulfoximines via ruthenium(II)-catalyzed enantioselective C-H functionalization assisted by C 1symmetric binaphthyl monocarboxylic acids L20 and L21 (Scheme 22). 48 This was the first report of a ruthenium(II)catalyzed asymmetric C-H functionalization via an enantiodetermining C-H cleavage step. A wide range of chiral sulfoximines was obtained in good to excellent yields and enantioselectivities via desymmetrization (Scheme 22a), kinetic resolution (Scheme 22b) and parallel kinetic resolution (Scheme 22c).…”