Diketone dynamic kinetic resolution

The enzyme-catalyzed regio- and enantioselective reduction of a- and/or y-alkyl-substituted p,5-diketo ester derivatives would enable the simultaneous introduction of up to four stereogenic centers into the molecule by two consecutive reduction steps through dynamic kinetic resolution with a theoretical maximum yield of 100%. Although the dynamic kinetic resolution of a-substituted P-keto esters by chemical [14] or biocatalytic [15] reduction has proven broad applicability in stereoselective synthesis, the corresponding dynamic kinetic resolution of 2-substituted 1,3-diketones is rarely found in the literature [16]. 

This indeed verifies the dynamic kinetic resolution of roc-3 through enzymatic reduction, representing the first example for the dynamic kinetic resolution of an open-chain 2-alkyl-substituted 1,3-diketone through reduction under neutral conditions. 

Scheme 12.21 One-pot synthesis of the corresponding 1,3 diols through dynamic kinetic resolution of diketone 40.

Eustache F, Dalko PI, Cossy J. Enantioselective monoreduction of 2-alkyl-1,3-diketones mediated by chiral ruthenium catalysts, dynamic kinetic resolution. Org. Lett. 2002 4 1263-1265. 

Fig. 8.40 One-pot reactions sequence, including hydrogenation of prochiral diketone 1,2-indanedione (I) with chemoenzymatic dynamic kinetic resolution of the resulting rac-2-hydroxy-l-indanone by racemization of (S)-2-hydroxy-l-indanone into (ff)-2-hydroxy-l-indanone and acylation of the latter to (ff)-2-acetoxy-l-indanone. (From O. Langvik, T. Sandberg, J. Wdrnd, D.Yu. Murzin, R. Leino, One-pot synthesis of (R)-2-acetoxy-l-indanone from 1,2-indanedione combining metai cataiyzed hydrogenation and chemoenzymatic dynamic kinetic resoiution, dynamic kinetic resoiution, Catai. Sci. Technoi 5 (2015) 150—160. Copyright the Royai Society of Chemistry).

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