Heterocycles 30: Lipase catalyzed kinetic resolution of racemic 1-(2-aryl-4-methyl-thiazol-5-yl)ethanols

The lipase mediated selective O-acylation and alcoholysis of the corresponding alcohols/butanoates have been investigated for the production of both (R)- and (S)-1-(2-aryl-thiazol-5-yl)ethanols. In terms of stereoselectivity and activity, CaL-B mediated selective acylation gave similar good results (c = 50%, E »200) in comparison with CaL-A mediated alcoholysis (c = 50%, E »200). Using the sequential kinetic resolution: first a CaL-B catalyzed (R)-selective O-acylation of racemic alcohols rac-2a–d followed by a CaL-A mediated methanolysis of the previously obtained enantiomerically enriched (R)-butanoates (R)-3a–d yielded (with 39–46% yields) both enantiopure forms of the 1-(2-aryl-thiazol-5-yl)ethanols.

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(S)-1-(4-Methyl-2-phenylthiazol-5-yl)ethanolC12H13NOS[α]D25=-53.4 (c 1.0, CHCl3)ee = 98.5% on Chiralpak IB HPLC columnSource of chirality: lipase catalyzed kinetic resolutionAbsolute configuration: (S)

(S)-1-(4-Methyl-2-m-tolylthiazol-5-yl)ethanolC13H15NOS[α]D25=-56 (c 1.0, CHCl3)ee = 98.5% on Chiralpak IB HPLC columnSource of chirality: lipase catalyzed kinetic resolutionAbsolute configuration: (S)

(S)-1-(4-Methyl-2-p-tolylthiazol-5-yl)ethanolC13H15NOS[α]D25=-54 (c 1.0, CHCl3)ee = 92% on Chiralpak IC HPLC columnSource of chirality: lipase catalyzed kinetic resolutionAbsolute configuration: (S)

(S)-1-(2-(4-Bromophenyl)-4-methylthiazol-5-yl)ethanolC12H12BrNOS[α]D25=-40 (c 1.0, CHCl3)ee = 91.5% on Chiralpak IC HPLC columnSource of chirality: lipase catalyzed kinetic resolutionAbsolute configuration: (S)

(R)-1-(4-Methyl-2-phenylthiazol-5-yl)ethyl butanoateC16H19NO2S[α]D25=+152 (c 1.0, CHCl3)ee = 98% on Chiralpak IB HPLC columnSource of chirality: lipase catalyzed kinetic resolutionAbsolute configuration: (R)

(R)-1-(4-Methyl-2-m-tolylthiazol-5-yl)ethyl butanoateC17H21NO2S[α]D25=+144 (c 1.0, CHCl3)ee = 97% on Chiralpak IB HPLC columnSource of chirality: lipase catalyzed kinetic resolutionAbsolute configuration: (R)

(R)-1-(4-Methyl-2-p-tolylthiazol-5-yl)ethyl butanoateC17H21NO2S[α]D25=+167.6 (c 1.0, CHCl3)ee >99.5% on Chiralpak IC HPLC columnSource of chirality: lipase catalyzed kinetic resolutionAbsolute configuration: (R)

(R)-1-(2-(4-Bromophenyl)-4-methylthiazol-5-yl)ethyl butanoateC16H18BrNO2S[α]D25=+99.2 (c 1.0, CHCl3)ee = 96.2% on Chiralpak IC HPLC columnSource of chirality: lipase catalyzed kinetic resolutionAbsolute configuration: (R)