The first enzymatic resolution of quaternary α-acetoxy α-substituted cyclic ketones

The enantioselective resolution of quaternary α-acetoxy α-substituted indanone and 1-tetralone derivatives was performed with commercially available enzyme CRL in pH = 8.0 phosphate buffer. Various parameters that would affect the enantoselectivities were tested, and the optimal enzymatic resolution condition was found to afford the enantiomerically enriched quaternary acetoxylated substrates with high ees (varied between 81% and 85%).

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(R)-(+)-2-Acetoxy-2-ethyl-indanoneC13H14O3Ee = 83%[α]D20=+14.8 (c 1.0, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: 2R

(R)-(+)-2-Acetoxy-2-methyl tetraloneC13H14O3Ee = 81%[α]D20=+2.6 (c 1.0, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: 2R

(+)-2-Acetoxy-2-acetyl-1-tetraloneC14H14O4Ee = 85%[α]D20=+4.4 (c 1.0, CHCl3)Source of chirality: enzymatic resolution