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

Article abstract of DOI:10.1021/jo990795w

Compound 1, (2,3-dihydro-3- (4′-hydroxyphenyl)-1,1,3-trimethyl-1H-inden-5-ol), a highly valuable monomer was prepared for the first time into its two enantiomerically pure forms via enzyme catalyzed kinetic resolution of corresponding 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 quaternary chiral center (five bonds), yielding (S)-(-)-1-4′-monopentanoate and unreacted (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)-C-)-1, showing that the reaction is also highly chemical selective between 1-diester and 1-monoester. The structural preference of the reaction was clearly determined by ¹H 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 derivatives. Surprisingly, CVL favors the carbonyl group on the more substituted phenol, which has more steric hindrance, shorter bond length (1.39 A compared to 1.41 A on less substituted phenyl), and was believed to be the less favored group. In brief, in this reaction, the more substituted phenol group is preferred. (S)-enantiomer is preferred. 1-Diesters are substrates while corresponding 1-monoesters are not. The unique feature of CVL provides a simple access to enantiopure diol 1, corresponding 1-monoestesrs, 1-homodiesters, as well as 1-mixed diesters.