First preparation of enantiopure indane monomer, (S)- (-)- and (R)-(+)-2,3-dihydro-3-(4 '-hydroxyphenyl)-1,1,3-trimethyl-1H-inden-5-ol, via a unique enantio- and regioselective enzymatic kinetic resolution

Compound 1, (2,3-dihydro-3- (4'-hydroxyphenyl)-1,1,3-trimethyl-1H-inden-5-o l), a highly valuable monomer was prepared for the first time into its two enantiomerically pure forms via enzyme catalyzed kinetic resolution of corr esponding 1-diesters. Hydrolysis of 1-dipentanoate catalyzed by lipase from Chromobacterium viscosum (CVL) is highly regioselective (38:1) between two phenyl groups and highly enantioselective (E = 48) toward a remote quatern ary chiral center (five bonds), yielding (S)-(-)-1-4-monopentanoate and unr eacted (R)-(+)-1-dipentanoate in high yield and excellent ee. Unlike other hydrolase-catalyzed reactions, the CVL-catalyzed reaction does not proceed to sequential hydrolysis of (S)-(-)-1-4'-monopentanoate to (S)-(-)-1, showi ng that the reaction is also highly chemical selective between 1-diester an d 1-monoester. The structural preference of the reaction was clearly determ ined by H-1 and COSY NMR. The absolute configuration of the nonreacted (R)- (+)-1-dipentanoate was determined consistently by circular dichroism and X- ray crystallography after being chemically transformed to (R)-(+)-1 and der ivatives. Surprisingly, CVL favors the carbonyl group on the more substitut ed phenol, which has more steric hindrance, shorter bond length (1.39 Angst rom compared to 1.41 Angstrom on less substituted phenyl), and was believed to be the less favored group. In brief, in this reaction, the more substit uted phenol group is preferred. (S)-enantiomer is:preferred. l-Diesters are substrates while corresponding 1-monoesters are not. The unique feature of CVL provides a simple access to enantiopure dial 1, corresponding 1-monoes tesrs, 1-homodiesters, as well as 1-mixed diesters.