Practical Asymmetric Synthesis of Chiral Sulfoximines via Sulfur-Selective Alkylation

Abstract

Chiral sulfoximines have recently been considered as promising bioisosteres in medicinal chemistry. However, methods for preparing chiral sulfoximines in a stereoselective manner are underdeveloped. Herein, we demonstrate an asymmetric synthesis of chiral sulfoximines through a stereospecific S-alkylation of readily accessible chiral sulfinamides under practical conditions. A key to establishing the practical conditions was the identification of the intermediate structure in our previously reported S-alkylation by X-ray crystallographic analysis.

Preparation of Sulfilimines by Sulfur-Alkylation of N-Acyl Sulfenamides with Alkyl Halides

“…The presence of nucleophilic N and S sites can pose a challenge in regioselectivity as previously demonstrated by Maruoka and co-workers in their work on the alkylation of N -acyl sulfinamides . Relevant to this investigation, Li and co-workers recently reported a study on the selective S -alkylation of N -acyl sulfenamides employing alkyl halides under aqueous conditions (Scheme C) .…”

Overlooked aza-S(iv) motifs: synthesis and transformations of sulfinamidines and sulfinimidate esters

“…35 Moreover, sulfinimidate esters have also been reported as byproducts or as sulfonium salts. 36,37 As highlighted in this summary, the synthesis of sulfinimidate esters has presented considerable limitations for quite some time. However, we have recently made a noteworthy contribution to advancing the field of sulfinimidate chemistry by uncovering a simple method.…”

Practical Asymmetric Synthesis of Sulfoximines and Sulfimides from Sulfinamides

“…Under optimized conditions, various enantioenriched sulfoximines 2 could be obtained by the S -alkylation of optically pure sulfinamides ( S )- 1 without racemization (Scheme 2a ). 9a c 15 To our delight, N -pivaloyl-protected sulfinamides were also applicable to the Cu-catalyzed S -selective arylation with diaryliodonium salts as precursors of highly electrophilic aryl species (Scheme 2b ). 9b Readily accessible N -pivaloyl-protected ( R )- tert -butylsulfinamide 1b , obtained from commercially available ( R )- tert -butylsulfinamide, was converted into ( S )-alkyl or arylsulfinamides ( S )- 1 without racemization by S -alkylation or S -arylation and a subsequent de- tert -butylation with CF 3 CO 2 H (Scheme 2c ).…”