Chloroperoxidase-catalyzed asymmetric synthesis of series of aromatic cyclic sulfoxides

Abstract

Abstract The chloroperoxidase (CPO) catalyzed oxidation of a series of rigid aromatic sulfides of well-defined geometry has been studied by the use of enantioselective gas chromatography for the determination of product composition and sulfoxide enantiomeric excess. The almost planar 1-thiaindane was found to be an excellent substrate, giving a quantitative yield of the (−)-(R)-1-oxide in 99% e.e. The sterically more demanding next higher homolog with a six-membered heterocyclic ring, 1-thiatetrahydronaphthalene (1-thiochroman), also gave a sulfoxide in high e.e (≥96%) but in a much lower yield, indicating a preserved stereorecognition ability but a lower turnover rate. A carbonyl group in the 4-position (1-thiochroman-4-one) had no further effect on the CPO-mediated sulfoxidation. Enantioselectivity was lost for the symmetric disulfide, 1,3-benzodithiol, indicating an equal accessibility of the FeO complex towards both sulfur atoms and an active site centred above the heme-iron atom. In all cases with pronounced enantioselectivity the reaction gave the (R)-sulfoxide as observed previously with alkyl aryl sulfides. A change of oxygen source from hydrogen peroxide to t-butyl hydroperoxide and a longer reaction time gave a higher chemical but a lower optical yield, most likely due to an increased competition by the uncatalyzed oxidation reaction in this case.