Deracemization of 1,2-diol monotosylate derivatives by a combination of enzymatic hydrolysis with the Mitsunobu inversion using polymer-bound triphenylphosphine

The deracemization of 1,2-diol monotosylate derivatives is achieved by the sequential combination of enzymatic hydrolysis and Mitsunobu inversion using a polymer-bound triphenylphosphine. After the lipase-catalysed hydrolysis of the racemic 2-acetoxyhexyl tosylate, the subsequent Mitsunobu reaction without separation causes an inversion of the resulting (R)-alcohol to give the (S)-enantiomer of the acetate as a single product. In particular, the reaction using the polymer-bound triphenylphosphine also proceeds smoothly, and the product is easily separated by filtration from the polymer-bound reagent and its by-products. This deracemization process is applicable to the preparation of several optically active 1,2-diol monotosylates.

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(S)-2-Acetoxyhexyl tosylateC15H22O5SEe = >99%[α]D23=-16.3 (c 1.26, CHCl3)Source of chirality: enzymatic hydrolysisAbsolute configuration: (S)

(S)-2-Hydroxyhexyl tosylateC13H20O4SEe = >99%[α]D29=+8.5 (c 1.08, CHCl3)Source of chirality: enzymatic hydrolysisAbsolute configuration: (S)

(S)-2-Benzoyloxyhexyl tosylateC20H24O5SEe = 99%[α]D25=+11.6 (c 1.01, CHCl3)Source of chirality: enzymatic hydrolysisAbsolute configuration: (S)

(S)-2-Acetoxypropyl tosylateC12H16O5SEe = >99%[α]D29=-13.5 (c 1.35, CHCl3)Source of chirality: enzymatic hydrolysisAbsolute configuration: (S)

(S)-2-Acetoxy-3-(4-methoxy)benzyloxypropyl tosylateC20H24O7SEe = >99%[α]D27=+4.6 (c 1.46, CHCl3)Source of chirality: enzymatic hydrolysisAbsolute configuration: (S)

(R)-2-Acetoxy-3-chloropropyl tosylateC12H15O5SClEe = >99%[α]D28=-5.4 (c 0.99, CHCl3)Source of chirality: enzymatic hydrolysisAbsolute configuration: (R)