Synthesis of enantioenriched sulfoxides

Abstract

This review discusses strategies for the asymmetric synthesis of sulfoxides, compounds with many applications in stereoselective synthesis and in some cases with pharmaceutical application. The review describes asymmetric oxidation, including metal catalyzed and nonmetal and biological oxidation processes, in addition to synthetic approaches via nucleophilic substitution of appropriately substituted precursors. Kinetic resolution in oxidation of sulfoxides to the analogous sulfones is also discussed; in certain instances, access to enantioenriched sulfoxides can be achieved via a combination of asymmetric sulfide oxidation and complementary kinetic resolution in sulfoxide oxidation.

Recommended Tests for the Self-Disproportionation of Enantiomers (SDE) to Ensure Accurate Reporting of the Stereochemical Outcome of Enantioselective Reactions

“…One might speculate on how many reports on the catalytic asymmetric synthesis of sulfoxides may contain questionable, to say the least, data. Chiral sulfoxides are in extremely high demand in academic research and the chemical industry concerned with the design and development of new synthetic reagents [138][139][140][141], drugs [142,143], and functional materials [144][145][146][147][148]. Due to the highly polar nature of the S-O bond, scalemic sulfoxides are prone to the SDEvC, rendering the sulfoxide functionality an SDE-phoric group [81].…”

Stereoselective Synthesis of 2-Thio-3-Chloroacrylamides and Investigation of their Reactivity

“…On closer examination of the Oxone ® oxidation, it was clear that the initial diastereoselective oxidation was followed by selective oxidation of the minor sulfoxide (E)-16bii to the sulfone (E)-17b, leading to an enhancement of the diastereomeric excess of the sulfoxide (Scheme 20); kinetic resolution has been shown to enhance the enantioselectivity in sulfur oxidation. [15][16][17][18][19] The sulfoxide (E)-16bi was easily separated from the less polar sulfone (E)-17b by chromatography on silica gel. Oxidation of the minor diastereomer (E)-16bii occurs selectively, but not exclusively, as the extent of sulfone formation clearly indicates that (E)-16bi also undergoes oxidation.…”

Modern Stereoselective Synthesis of Chiral Sulfinyl Compounds

“… 5 − 7 A general review by Maguire and co-workers on the synthesis of enantioenriched sulfoxides, with a special attention paid to kinetic resolution, was published in 2011. 33 Several articles were devoted to asymmetric oxidations, including sulfoxidations, with a focus on environmentally benign methods. 34 − 36 A first part of a paper in which Franklin Davis described his “adventures in sulfur–nitrogen chemistry” (using his own words) described the preparation and use of chiral oxaziridine derivatives (known as Davis reagents) in enantioselective oxidation of sulfenyl compounds: sulfides, disulfides, and sulfenylimines.…”