Dynamic Enzymatic Kinetic Resolution of Methyl 2,3-Dihydro-1H-indene-1-carboxylate

A new reaction setup for kinetic enzymatic resolution was established and is demonstrated for the case of the hydrolase-catalysed conversion of methyl 2,3-dihydro-1H-indene1-carboxylate (1) in conjunction with a base-catalysed racemisation. The system allows controlled racemisation, resulting in efficient dynamic kinetic resolution (DKR) of the title compound. Short reaction times and high enantioselectivities were obtained with CAL-B and TBD (1,5,7-tri-azabicyclo[4.4.0]dec-5-ene). Compound (R)-1 (ee 95%) served as a starting material in a domino reaction that led to the biaryl indanyl ketone (R)-8, a lead compound for novel inhibitors of peptidyl-prolyl-cis/trans-isomerases, in 94 % ee. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)