Efficient, scalable asymmetric synthesis of an epoxy quinol via Noyori desymmetrization of a meso diketone

Epoxy quinol 1a was prepared on a multi-gram scale by Noyori transfer hydrogenative desymmetrization of the readily available meso-epoxy diketone 4. Although the intrinsic enantioselectivity for the desymmetrization was modest (82:18 er at 4% conversion), a highly enantiopure product (99.6:0.4 er) could be obtained in one operation in 44% yield via kinetic resolution of the minor enantiomer with long reaction times (48 h), or in 73% yield by combination with an enzymatic resolution of a 93:7 er mixture.

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(1S,5R,6S)-5-Hydroxy-7-oxabicyclo[4.1.0]hept-3-en-2-oneC6H6O3Ee > 99%[α]D19=+3.8 (c 1.65, CH2Cl2)Source of chirality: Noyori asymmetric transfer hydrogenationAbsolute configuration: (1S,5R,6S)