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
M. Zhang et R. Kazlauskas, 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, J ORG CHEM, 64(20), 1999, pp. 7498-7503
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.