The synthesis of chiral β-ketosulfoxides by enantioselective oxidation and their stereocontrolled reduction to β-hydroxysulfoxides

Various chiral non-racemic β-ketosulfoxides, a class of compounds frequently used in asymmetric synthesis, were prepared in good yields by tert-butyl hydroperoxide oxidation of the corresponding sulfides in the presence of a complex between titanium and (S,S)-hydrobenzoin. The ee values of almost all of the purified products were >98%. As ascertained by X-ray analysis and/or by NMR spectroscopy, the use of the (S,S)-form of the ligand led to aryl β-ketosulfoxides with (RS)-configuration and to methyl phenacyl sulfoxide with the (SS)-configuration. Some of the aryl ketosulfoxides were subjected to reduction with DIBAL-H/ZnCl2 and the corresponding β-sulfinylalcohols with an (R,RS)-configuration produced.

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(R)-2-Naphthyl phenacyl sulfoxideC18H14O2SEe >98% (HPLC)[α]D25=+204.5 (c 1.01, CHCl3)Source of chirality: enantioselective oxidationAbsolute configuration: R

(R)-p-Bromophenyl phenacyl sulfoxideC14H11BrO2SEe >98% (HPLC)[α]D25=+174.3 (c 1.00, CHCl3)Source of chirality: enantioselective oxidationAbsolute configuration: R

(R)-o-Bromophenyl phenacyl sulfoxideC14H11BrO2SEe >98% (HPLC)[α]D25=+390.4 (c 1.01, CHCl3)Source of chirality: enantioselective oxidationAbsolute configuration: R

(R)-1-(2-Naphthylsulfinyl)-propan-2-oneC13H12O2SEe >98% (HPLC)[α]D25=+231.2 (c 0.99, CHCl3)Source of chirality: enantioselective oxidationAbsolute configuration: R

(R,RS)-1-Phenyl-2-(2-naphthylsulfinyl)-ethanolC18H16O2SDe >98% (HPLC)[α]D25=+55.2 (c 0.98, CHCl3)Source of chirality: diastereoselective reductionAbsolute configuration: (R,RS)

(R,RS)-1-Phenyl-2-(p-bromophenylsulfinyl)-ethanolC14H13BrO2SDe >98% (HPLC)[α]D25=+72.6 (c 0.99, CHCl3)Source of chirality: diastereoselective reductionAbsolute configuration: (R,RS)

(R,RS)-1-(2-Naphthylsulfinyl)-propan-2-olC13H14O2SDe = 86% (HPLC)[α]D25=+239 (c 1.00, CHCl3) for an 86% deSource of chirality: diastereoselective reductionAbsolute configuration: (R,RS) (predominant)