Kinetic resolution of primary alcohols having remote stereogenic centers: lipase mediated kinetic resolution of (±)-3-chloro-3-arylpropanols

Kinetic resolutions of (±)-3-chloro-3-arylpropanols by lipase mediated acetylation are described for the first time. Acetylation with CCL provided the best enantioselectivity amongst the enzymes used. Enantiomerically enriched products were obtained with up to 78% ee after two successive lipase-catalyzed acetylations. Different substituents on the aromatic ring and bromide, instead of chloride, on the substrates were found to have no drastic influence on the enantioselectivity of the reaction.

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(+)-3-Chloro-3-phenylpropan-1-olC9H11ClOEe = 78%[α]D25=+32.3 (c 1.00, CHCl3)Source of chirality: enzymatic resolution

(+)-3-Chloro-3-(4-fluorophenyl)propan-1-olC9H10ClFOEe = 21%[α]D25=+15.4 (c 1.90, CHCl3)Source of chirality: enzymatic resolution

(+)-3-Chloro-3-(4-chlorophenyl)propan-1-olC9H10Cl2OEe = 21%[α]D25=+10.0 (c 1.80, CHCl3)Source of chirality: enzymatic resolution

(+)-3-Chloro-3-(4-bromophenyl)propan-1-olC9H10BrClOEe = 23%[α]D25=+7.6 (c 1.40, CHCl3)Source of chirality: enzymatic resolution

(+)-3-Chloro-3-(2-fluorophenyl)propan-1-olC9H10ClFOEe = 25%[α]D25=+6.7 (c 1.40, CHCl3)Source of chirality: enzymatic resolution

(+)-3-Chloro-3-(2-bromophenyl)propan-1-olC9H10BrClOEe = 43%[α]D25=+4.4(c 1.00, CHCl3)Source of chirality: enzymatic resolution

(+)-3-Bromo-3-phenylpropan-1-olC9H11BrOEe = 21%[α]D25=+8.8 (c 0.99, CHCl3)Source of chirality: enzymatic resolution

(−)-3-Chloro-3-phenylpropyl acetateC11H13ClO2Ee = 33%[α]D25=-19.9 (c 1.20, CHCl3)Source of chirality: enzymatic resolution

(−)-3-Chloro-3-(4-fluorophenyl)propyl acetateC11H12ClFO2Ee = 32%[α]D25=-16.3 (c 1.40, CHCl3)Source of chirality: enzymatic resolution

(−)-3-Chloro-3-(4-chlorophenyl)propyl acetateC11H12Cl2O2Ee = 37%[α]D25=-19.7 (c 1.20, CHCl3)Source of chirality: enzymatic resolution

(−)-3-Chloro-3-(4-bromorophenyl)propyl acetateC11H12BrClO2Ee = 30%[α]D25=-11.2 (c 0.85, CHCl3)Source of chirality: enzymatic resolution

(−)-3-Chloro-3-(2-fluorophenyl)propyl acetateC11H12ClFO2Ee = 24%[α]D25=-18.0 (c 1.70, CHCl3)Source of chirality: enzymatic resolution

(−)-3-Chloro-3-(2-bromophenyl)propyl acetateC11H12BrClO2Ee = 36%[α]D25=-11.8 (c 1.40, CHCl3)Source of chirality: enzymatic resolution

(−)-3-Bromo-3-phenylpropyl acetateC11H13BrO2Ee = 38%[α]D25=-28.7 (c 0.84, CHCl3)Source of chirality: enzymatic resolution