Enantioselective Synthesis of 2,2-Disubstituted Terminal Epoxides via Catalytic Asymmetric Corey-Chaykovsky Epoxidation of Ketones

Abstract

Catalytic asymmetric Corey-Chaykovsky epoxidation of various ketones with dimethyloxosulfonium methylide using a heterobimetallic La-Li3-BINOL complex (LLB) is described. The reaction proceeded smoothly at room temperature in the presence of achiral phosphine oxide additives, and 2,2-disubstituted terminal epoxides were obtained in high enantioselectivity (97%–91% ee) and yield (>99%–88%) from a broad range of methyl ketones with 1-5 mol% catalyst loading. Enantioselectivity was strongly dependent on the steric hindrance, and other ketones, such as ethyl ketones and propyl ketones resulted in slightly lower enantioselectivity (88%–67% ee).

Catalytic Asymmetric Synthesis of Chiral Spiro‐cyclopropyl Oxindoles from 3‐Alkenyl‐oxindoles and Sulfoxonium Ylides

“…Shibasaki and Matsunaga described an enantioselective cyclopropanation of enones and an N ‐acylpyrrole with dimethyloxosulfonium methylide using La−Li 3 ‐(biphenyldiolate) 3 catalysts . The same group also reported the synthesis of chiral epoxides and oxetanes from ketones and dimethyloxosulfonium methylide catalyzed by the heterobimetallic catalysts –. Herein, we report our efforts in developing an N , N ′‐dioxide‐Mg(II) complex catalytic system for the catalytic asymmetric cyclopropanation of 3‐alkenyl‐oxindoles with sulfoxonium ylides to synthesize spiro‐cyclopropyl oxindole derivatives.…”

Asymmetric transformations from sulfoxonium ylides

“…In the last contribution of this series, the group further expanded the methodology with eight examples of 2,2′-disubstituted epoxides (100) from alkyl (ethyl, isopropyl and n -propyl) aryl ketones, in good yields (60–96%) and with good enantioselectivities (67–88% ee). 137 These reactions are believed to occur via dual control from a heterobimetallic chiral complex, with a simultaneous interaction with the ketone and DMSM, as highlighted in Scheme 14 .…”

Stereoselective Synthesis of Trisubstituted Epoxides Marks the Route to Chiral Building Blocks with Quaternary Centers

“…In contrast, and despite the fact that the epoxidation reaction of ketones was reported by Corey and Chaykovsky in 1962, only a couple of reports dealing with asymmetric epoxidation of ketones have enriched the chemistry literature , . In particular, a general asymmetric epoxidation of ketones yielding trisubstituted epoxides (Scheme b) remains unprecedented , . Having a quaternary carbon vicinal to another chiral center in optically active epoxides bequeaths important stereogenic properties to these building blocks as well as to the small molecules emanating from them and therefore calls for the development of an easy and efficient access to these small heterocycles.…”