Dynamic kinetic resolution of secondary aromatic alcohols with new efficient acyl donors

A new and efficient dynamic kinetic resolution (DKR) process of secondary aromatic alcohols by using long carbon-chain esters as acyl donors has been developed. During the process, the transesterification catalyzed by CD8604 was found to be the main reason for the decrease in enantiomeric excess (ee). Using complex acyl donors, such as 4-chlorophenyl valerate, we could effectively inhibit the resin-catalyzed transesterification, and an excellent ee value (>99%) at high yield (>99%) was achieved. The mechanism for the inhibition of resin-catalyzed transesterification is believed to be the formation of micro-micelles in the pores of CD8604. It is noteworthy that the system can be reused more than 20 times without a loss of yield or ee value.

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(R)-1-Phenylethanol valerateC13H18O2[α]D25=+69.1 (c 1.00, CH2Cl2)Source of chirality: enzymatic resolutionAbsolute configuration: (R)

(R)-1-(2-Methylphenyl)ethanol valerateC14H20O2[α]D25=+62.4 (c 1.00, CH2Cl2)Source of chirality: enzymatic resolutionAbsolute configuration: (R)

(R)-1-(4-Methylphenyl)ethanol valerateC14H20O2[α]D25=+71.3 (c 1.00, CH2Cl2)Source of chirality: enzymatic resolutionAbsolute configuration: (R)

(R)-1-(3,5-Dimethylphenyl)ethanol valerateC15H22O2[α]D25=+47.8 (c 1.00, CH2Cl2)Source of chirality: enzymatic resolutionAbsolute configuration: (R)

(R)-1-(2,4-Dimethylphenyl)ethanol valerateC15H22O2[α]D25=+43.2 (c 1.00, CH2Cl2)Source of chirality: enzymatic resolutionAbsolute configuration: (R)

(R)-1-(3,4-Dimethylphenyl)ethanol valerateC15H22O2[α]D25=+50.2 (c 1.00, CH2Cl2)Source of chirality: enzymatic resolutionAbsolute configuration: (R)

(R)-1-(2,3-Dimethylphenyl)ethanol valerateC15H22O2[α]D25=+44.3 (c 1.00, CH2Cl2)Source of chirality: enzymatic resolutionAbsolute configuration: (R)

(R)-1-(4-Chlorophenyl)ethanol valerateC13H17ClO2[α]D25=+69.1 (c 1.00, CH2Cl2)Source of chirality: enzymatic resolutionAbsolute configuration: (R)

(R)-1-(2-Chlorophenyl)ethanol valerateC13H17ClO2[α]D25=+41.3 (c 1.00, CH2Cl2)Source of chirality: enzymatic resolutionAbsolute configuration: (R)

(R)-1-(3-Chlorophenyl)ethanol valerateC13H17ClO2[α]D25=+63.3 (c 1.00, CH2Cl2)Source of chirality: enzymatic resolutionAbsolute configuration: (R)

(R)-1-(4-Bromophenyl)ethanol valerateC13H17BrO2[α]D25=+63.5 (c 1.00, CH2Cl2)Source of chirality: enzymatic resolutionAbsolute configuration: (R)

(R)-1-(4-Methoxyphenyl)ethanol valerateC14H20O3[α]D25=+95.7 (c 1.00, CH2Cl2)Source of chirality: enzymatic resolutionAbsolute configuration: (R)

(R)-1-(3,4-Dimethoxyphenyl)ethanol valerateC15H22O4[α]D25=+86.5 (c 1.00, CH2Cl2)Source of chirality: enzymatic resolutionAbsolute configuration: (R)

(R)-1-(3,4-Methylenedioxy)ethanol valerateC14H18O4[α]D25=+64.6 (c 1.00, CH2Cl2)Source of chirality: enzymatic resolutionAbsolute configuration: (R)