title: Chemo- and enantioselective routes to chiral fluorinated hydroxyketones using ketoreductases.
abstract: Chiral fluorinated hydroxyketones were synthesized with excellent ee (>98%) and yield by a chemo- and stereoselective reduction of prochiral methyl/trifluoromethyl diketones using commercially available ketoreductase enzymes. By using p- and m-trifluoroacetyl substituted acetophenones, we demonstrate that ketoreductases can selectively differentiate between methyl and trifluoromethyl ketones within the same molecule. As a result, useful catalysts were identified that eliminated the need for costly and time-consuming protection/deprotection of the ketone moiety, enabling a more convergent synthesis of hydroxyketones. Further, a route to chiral methyl hydroxyketones is provided where an enzyme selectively reduces the unactivated ketone.
authors.affiliation: Department of Process Research, Merck Research Laboratories, Merck and Co., Inc., PO Box 2000, Rahway, New Jersey 07065, USA. brendan_grau@merck.com
authors.forename: Brendan T
authors.initials: BT
authors.lastname: Grau
authors.forename: Paul N
authors.initials: PN
authors.lastname: Devine
authors.forename: Lisa N
authors.initials: LN
authors.lastname: DiMichele
authors.forename: Birgit
authors.initials: B
authors.lastname: Kosjek
mesh_terms: D002384:Catalysis; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis* / Q000737:chemistry; D007659:Ketones / Q000138:chemical synthesis* / Q000737:chemistry; D010088:Oxidoreductases / Q000737:chemistry*; D013237:Stereoisomerism; D013997:Time Factors
chemical_list: D006845:Hydrocarbons, Fluorinated; D007659:Ketones; D010088:Oxidoreductases