Methods for the synthesis of chiral sulfur heterocycles and their application in the asymmetric Baylis–Hillman reactions

Enantiomerically pure (2S,6S)-2,6-diphenyltetrahydro-2H-thiopyran, (2S)-2-phenyltetrahydro thiophene, and (2S)-2-phenyltetrahydro-2H-thiopyran were prepared in 70–72% yields and with 86–99% ee via cyclization of the corresponding dimesylate in an SN2 cyclization reaction using sodium sulfide nonahydrate. The results on the application of various chiral sulfides in asymmetric Baylis–Hillman reactions are also described.

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(2S,6S)-2,6-Diphenyltetrahydro-2H-thiopyranC17H18SEnantiomeric excess = >99%[α]D25=+36.9 (c 1.04 CHCl3)Source of chirality: Enantioselective synthesisAbsolute configuration: (2S,6S)

(2S,6S)-2,6-Diphenyltetrahydro-2H-thiopyran-1,1-dioxideC17H18O2SEnantiomeric excess = >99%[α]D25=-41.4 (c 0.39 CHCl3)Source of chirality: Enantioselective synthesisAbsolute configuration: (2S,6S)

(2S)-PhenyltetrahydrothiopheneC10H12SEnantiomeric excess = 93%[α]D25=+28.2 (c 2.0, CH2Cl2)Source of chirality: Enantioselective synthesisAbsolute configuration: (2S)

(2S)-Phenyltetrahydrothiophene-1,1-dioxideC10H12O2SEnantiomeric excess = 93%[α]D25=-24.7 (c 0.58 CHCl3)Source of chirality: Enantioselective synthesisAbsolute configuration: (2S)

(2S)-2-Phenyltetrahydro-2H-thiopyranC11H14SEnantiomeric excess = 86%[α]D25=-31.2 (c 0.84 CHCl3)Source of chirality: Enantioselective synthesisAbsolute configuration: (2S)

(R)-3-[Hydroxy-(4-nitro-phenyl)-methyl]-but-3-en-2-oneC11H11NO4Enantiomeric excess = 54%[α]D25=-9.3 (c 0.4, CHCl3)Source of chirality: Enantioselective synthesisAbsolute configuration: (R)

(R)-3-[Hydroxy-(2-nitro-phenyl)-methyl]-but-3-en-2-oneC11H11NO4Enantiomeric excess = 22%[α]D25=-35.2 (c 0.25, CHCl3)Source of chirality: Enantioselective synthesisAbsolute configuration: (R)

(R)-3-[Hydroxy-(3-nitro-phenyl)-methyl]-but-3-en-2-oneC11H11NO4Enantiomeric excess = 37%[α]D25=-9.2 (c 0.38, CHCl3)Source of chirality: Enantioselective synthesisAbsolute configuration: (R)

(R)-3-[Hydroxy-(4-chloro-phenyl)-methyl]-but-3-en-2-oneC11H11ClO2Enantiomeric excess = 24%[α]D25=-9.0 (c 1.06, CHCl3)Source of chirality: Enantioselective synthesisAbsolute configuration: (R)

(R)-3-[Hydroxy-(4-bromo-phenyl)-methyl]-but-3-en-2-oneC11H11BrO2Enantiomeric excess = 42%[α]D25=-16.8 (c 0.46, CHCl3)Source of chirality: Enantioselective synthesisAbsolute configuration: (R)

(R)-3-[Hydroxy-(4-cyano-phenyl)-methyl]-but-3-en-2-oneC12H11NO2Enantiomeric excess = 55%[α]D25=-13.9 (c 0.27, CHCl3)Source of chirality: Enantioselective synthesisAbsolute configuration: (R)

(R)-3-[Hydroxy-(4-trifluoromethyl-phenyl)-methyl]-but-3-en-2-oneC12H11F3O2Enantiomeric excess = 32%[α]D25=-6.3 (c 0.5, CHCl3)Source of chirality: Enantioselective synthesisAbsolute configuration: (R)

(R)-3-[Hydroxy-phenyl-methyl]-but-3-en-2-oneC11H12O2Enantiomeric excess = 48%[α]D25=-12.0 (c 0.40, CHCl3)Source of chirality: Enantioselective synthesisAbsolute configuration: (R)

(R)-3-(Furan-2-yl(hydroxy)methyl)but-3-en-2-oneC9H10O3Enantiomeric excess = 14%[α]D25=-2.8 (c 0.40, CHCl3)Source of chirality: Enantioselective synthesisAbsolute configuration: (R)