ol401606x_si_002.pdf (2.74 MB)
One-Pot Synthesis of Enantiopure 3,4-Dihydroisocoumarins through Dynamic Reductive Kinetic Resolution Processes
journal contributionposted on 2013-08-02, 00:00 authored by Juan Mangas-Sánchez, Eduardo Busto, Vicente Gotor, Vicente Gotor-Fernández
A straightforward chemoenzymatic synthesis of enantiopure 4-alkyl-3-methyl-3,4-dihydroisocoumarins through a ketoreductase-catalyzed one-pot dynamic reductive kinetic resolution is reported. E. coli/ADH-A cells have shown outstanding diastereo- and enantioselectivity toward the bioreduction of a series of racemic ketones, with the use of anion exchange resins or triethylamine being compatible in the same aqueous reaction medium. The so-obtained enantiopure alcohols were subsequently cyclized in acid media affording the corresponding lactones in good to excellent conversions (72–96%) and excellent selectivities (dr ≥99:1 and ee >99%).