Selected racemic trans-2-alkoxycarbonyl-3,6-dihydro-2H-moderate to high enantiomeric purities (up to 95%). The enantioselectivity of the reaction was found to be strongly thiopyran S-oxides 2a-h have been subjected to enzymeassisted hydrolysis under conditions of kinetic resolution to dependent on the structures of the substrates used. give the corresponding acids and recovered esters with
Optically active sulfoxides have proved to be a very useful tool in asymmetric carbonϪcarbon and carbonϪheteroatom bond formation and have thus found widespread application in asymmetric and stereoselective synthesis. [1] Since there is a strong demand for a great diversity of sulfoxides, the development of efficient and general methods for their synthesis remains an ongoing subject of research Scheme 1. Synthesis of thiopyran S-oxides 2 for organic chemists.
Among the many synthetic methodologies, those emies. [12] [13] In the present paper, we focus on the scope and ploying enzymes have recently become a valuable suplimitations of our approach. plement. Thus, in addition to the well-known enzymatic oxidation of unsymmetrical sulfides, [2] [3] enzyme-mediated Results and Discussion kinetic resolution of a variety of sulfinylcarboxylates and acyloxy sulfoxides has been achieved, using commonly Of the available cyclic sulfoxides, suitable substrates were available hydrolytic enzymes. [4Ϫ8] Furthermore, we have selected for hydrolysis in the presence of some readily availdemonstrated that the enzymatic methodology is also suitable enzymes. In all cases, the substrates employed were sinable for the enantioselective hydrolysis of prochiral sulfinylgle trans diastereomers (vide infra). The experiments were dicarboxylates. [9] performed in buffer solutions using an automatic titrator to In our search for new types of sulfinylcarboxylates to use maintain the appropriate pH value. The reactions were usuas substrates for enzymatic hydrolysis, we decided to investially carried out until 50% conversion was reached, although gate whether certain representatives of cyclic, six-membered in some cases they were deliberately stopped at different sulfoxides, namely 2-alkoxycarbonyl-3,6-dihydro-2H-thiopstages to obtain a better ee of either the unchanged ester or yran 1-oxides 2, could serve this purpose. It should be the hydrolysis product. The ee values of 2* were determined pointed out that these compounds have been the subject of from the 1 H-NMR spectra of their complexes with (ϩ)-(R)detailed investigations by Zwanenburg et al. [10] and are eastert-butylphenylphosphinothioic acid, which is a versatile ily obtainable as single diastereomers through cycloaddition chiral solvating agent, [14a] especially for sulfoxides. [14b,14c] It reactions of butadienes with appropriate α-oxo sulfines 1 also proved to be the reagent of choice in the case of cyclic (Scheme 1). [11] sulfoxides. The results are summarized in Scheme 2 and collected in Table 1. In our preliminary accounts, we reported the enzymatic resolution of three representatives of these types of substrates and the results of X-ray crystallographic stud- [a