Synthesis of optically active heterocyclic compounds via deracemization of 1,2-diol monotosylate derivatives bearing a long aliphatic chain by a combination of enzymatic hydrolysis with Mitsunobu inversion

We have succeeded in accomplishing the deracemization of (±)-2-acetoxydecyl and (±)-acetoxy-6-benzyloxyhexyl tosylates, which have a long substituent, via an enzyme-mediated enantioselective hydrolysis with a Mitsunobu inversion using polymer-supported triphenylphosphine to afford the corresponding (S)-enantiomer. Enantiomerically pure (S)- and (R)-γ-dodecalactones, a fruit flavor, were synthesized from (S)-2-acetoxydecyl tosylate as the mutual starting material. The poisonous alkaloid (S)-coniine was also synthesized using enantiomerically pure allyl amine as the key intermediate derived from (S)-acetoxy-6-benzyloxyhexyl tosylate.

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(S)-2-Acetoxydecyl tosylateC19H30O5See = >99%[α]D23=-13.7 (c 0.58, CHCl3)Source of chirality: enzymatic hydrolysisAbsolute configuration: (S)

(S)-2-Acetoxy-6-benzyloxyhexyl tosylateC22H28O6See = >99%[α]D29=-9.7 (c 2.7, CHCl3)Source of chirality: enzymatic hydrolysisAbsolute configuration: (S)

(S)-2-OctyloxiraneC10H20Oee = >99%[α]D26=-8.2 (c 1.03, CHCl3)Source of chirality: enzymatic hydrolysisAbsolute configuration: (S)

(S)-1-Tridecen-5-olC13H26Oee = >99%[α]D24=-3.0 (c 1.05, MeOH)Source of chirality: enzymatic hydrolysisAbsolute configuration: (S)

(S)-γ-DodecalactoneC12H22O2ee = >99%[α]D21=-43.1 (c 1.01, MeOH)Source of chirality: enzymatic hydrolysisAbsolute configuration: (S)

(S)-2-Hydroxydecyl tosylateC17H28O4See = >99%[α]D27=+5.7 (c 1.73, CHCl3)Source of chirality: enzymatic hydrolysisAbsolute configuration: (S)

(S)-2-(4-Benzyloxybutyl)oxiraneC13H18O2ee = >99%[α]D26=-5.3 (c 1.14, CHCl3)Source of chirality: enzymatic hydrolysisAbsolute configuration: (S)

(S)-8-Benzyloxyoct-1-en-4-olC15H22O2ee = >99%[α]D26=-3.9 (c 0.69, CHCl3)Source of chirality: enzymatic hydrolysisAbsolute configuration: (S)

(R)-8-Benzyloxy-4-(tert-butoxycarbonyl)aminooct-1-eneC20H31NO3ee = >99%[α]D26=+13.8 (c 1.04, CHCl3)Source of chirality: enzymatic hydrolysisAbsolute configuration: (R)

(S)-N-tert-Butoxycarbonyl-2-propylpiperidineC13H25NO2ee = >99%[α]D25=+30.9 (c 0.98, CHCl3)Source of chirality: enzymatic hydrolysisAbsolute configuration: (S)

(S)-Coniine, hydrochlorideC8H18N·HClee = >99%[α]D20=+5.7 (c 1.12, EtOH)Source of chirality: enzymatic hydrolysisAbsolute configuration: (S)