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

Michael Zhang, Romas Kazlauskas

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

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 aria 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, 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 bona length (1.39 Å compared to 1.41 Å 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.

Original languageEnglish (US)
Pages (from-to)7498-7503
Number of pages6
JournalJournal of Organic Chemistry
Volume64
Issue number20
DOIs
StatePublished - Oct 1 1999

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