Chemoenzymatic Stereodivergent Synthesis of All the Possible Stereoisomers of the 2,3-Dimethylglyceric Acid Ethyl Ester

2,3-dihydroxy-2-methylbutyric acid, also known as 2,3-dimethylglyceric constitutes the acyl and/or alcoholic moiety of many bioactive natural esters. Herein, we describe a chemoenzymatic methodology which gives access to all four possible stereoisomers acid ethyl ester. The racemic ?-acetolactate, produced by N-heterocycle carbene (NHC)-catalyzed coupling pyruvate and methylacetoin was employed starting material. mixture resolved through (S)-selective reductions, promoted acetylacetoin reductase (AAR) affording resulting (2R,3S)-2,3-dimethylglycerate; isolated remaining (S)-ethyl ?-acetolactate successively treated with baker’s yeast obtain corresponding (2S,3S) stereoisomer. syn-2,3-Dimethylgliceric ester afforded reducing rac-?-acetolactate NaBH4 in presence ZnCl2 kinetically selective acetylation lipase B from Candida antarctica (CAL-B) vinyl acetate (2S,3R) Finally, (2R,3R) stereoisomer, prepared C3 epimerization (2R,3S) stereoisomer recovered above kinetic resolution, achieved TEMPO-mediated oxidation, followed reduction ketone NaBH4. 2,3-dimethylglycertate enriched submitted stereospecicific CAL-B order separate major entire procedure enabled conversion into enantiopure 2,3-dihydroxy-2-methylbutyrate following overall yields: 42% for (2R,3S), 40% (2S,3S), 20% (2R,3R).