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).
Highlights
Active epoxides are versatile chiral building blocks for the efficient synthesis of natural products and biologically active compounds such as pharmaceuticals
We hypothesized that the dual control of two reactants [18], ketones and sulfur ylide, by a doubly Lewis acidic bimetallic/multimetallic complexes would be beneficial over a conventional method based on the activation of ketone alone with a mono-metallic chiral Lewis acid catalyst
After evaporating solvent under reduced pressure, the residue was purified by flash column chromatography to give product 4 [Caution: Most of the epoxides are somewhat unstable under acidic conditions
Summary
Active epoxides are versatile chiral building blocks for the efficient synthesis of natural products and biologically active compounds such as pharmaceuticals. Catalytic asymmetric epoxidations of geminally disubstituted terminal unfunctionalized alkenes (eq 1, Scheme 1) have been studied using enzymes [3,4], chiral metal- and organo-catalysts [5,6,7], but the enantioselectivity, yield, and/or substrate generality of these reactions are not satisfactory. One of the best chiral catalysts for asymmetric epoxidation of geminally disubstituted terminal unfunctionalized alkenes was developed in 2008 by Shi and co-workers. In their system, good enantioselectivity was achieved with -t-Bu-substituted styrene (86% ee), but smaller substituents, especially -Me-substituted styrene, resulted in moderate enantioselectivity [8].
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