Chemo-enzymatic Dynamic Kinetic Resolution Of Secondary Alcohols

In this paper, two kinds of acid catalysts were chosen as racemization catalysts and the catalytic performance were investigated. And the two kinds of acid catalysts could be applied to the DKR of several secondary aromatic alcohols successfully. The main conclusions were as follows:Two acid resins with highly efficient racemization activity were screened and showed great potential to apply to the DKR of secondary aromatic alcohols. They could racemize (S)-1-phenylethanol almost completely in 6.5h at 40℃.A series of phenyl acetate derivatives were synthesized and investigated for increasing the eep. And the selectivity of the DKR of 1-phenylethanol really could be successfully enhanced by using more complex acyl donors to inhibit the acid resin-catalyzed transesterification. When 1,3-Diacetoxybenzene and CD 8604 was used as acyl donor and racemization catalyst respectively, good yield (>99%) and high ee value of product (95.8%) were obtained. Good results were also obtained when 1,2-Diacetoxybenzene and 3,5-dimethyl phenyl acetate as acyl donors.To expand the application area of the results, several substrates with different substitution groups on its benzene ring were tested and most DKR of them were performed successfully. For 1-(3,5-dimethylphenyl)ethanol, when 4-chlorophenyl acetate and CD 550 was used as acyl donor and racemization catalyst respectively, the product with 97.4%ee could be obtained in nearly 99% yield. When CD8604was used as racemization catalyst, the ee value of product was 96.5% with nearly the same yield as CD550.Solid superacid Fe2O3/SO42- was prepared as racemization catalyst with excellent racemization capacity and also showed great potential to apply to DKR of several secondary aromatic alcohols.The DKR of 1-phenylethanol catalyzed by lipase Novozym435-solid superacid Fe2O3/SO42- combo was established successfully, when 4-chlorophenyl acetate as acyl donor, good yield (>99%) and high ee value of product (95.4%) were obtained after 3h's reaction. While 3,5-dimethyl phenyl acetate as acyl donor, the yield and ee value of product was 90.5% and 95.1% respectively after 12h's reaction.The Novozym435-solid superacid Fe2OSO42- combo catalyzed DKR system was also suitable for several secondary aromatic alcohols. For different substrates, appropriate acyl donor that gave good result was different. For DKR of 1-(3,5-dimethylphenyl)ethanol, the appropriate acyl donor was still 4-chlorophenyl acetate. After 3h's reaction, the yield and ee value of product was>99% and 93.7% respectively.(RS)-4-hydroxy-3-methyl-2-(2'-propynyl)-2-cyclopentenone acetate was successfully resoluted by lipase-catalyzed alcoholysis through adjusting the basicity of organic reaction system, and the product was obtained in both high conversion and ee value. This information made good preparation for the DKR of (RS)-4-hydroxy-3-methyl-2-(2'-propynyl)-2-cyclopentenone.