Racemic sulfinyl chloride

A new and general approach to chiral aliphatic or aromatic sulfinates has been recently described by Mikofajczyk and Drabowicz (107). It consists of the asymmetric condensation of racemic sulfinyl chlorides at low temperature with achiral alcohols in the presence of chiral tertiary amines as asymmetric reagents. The optical purity (up to 45%) of the sulfinates formed is strongly dependent on the structure of all the reaction components. 

Sharpless and Klunder22 are developing a new procedure for conversion of sulfonyl chlorides directly into menthyl sulflnate esters using trimethyl phosphite as a reducing agent (equation 2). This method, starting with sulfonyl chlorides rather than with the much less available sulfinyl chlorides, should allow access to an even wider range of sulfinate esters and, ultimately, to various chiral, non-racemic sulfoxides. 

Mikolajczyk and coworkers have summarized other methods which lead to the desired sulfmate esters These are asymmetric oxidation of sulfenamides, kinetic resolution of racemic sulfmates in transesterification with chiral alcohols, kinetic resolution of racemic sulfinates upon treatment with chiral Grignard reagents, optical resolution via cyclodextrin complexes, and esterification of sulfinyl chlorides with chiral alcohols in the presence of optically active amines. None of these methods is very satisfactory since the esters produced are of low enantiomeric purity. However, the reaction of dialkyl sulfites (33) with t-butylmagnesium chloride in the presence of quinine gave the corresponding methyl, ethyl, n-propyl, isopropyl and n-butyl 2,2-dimethylpropane-l-yl sulfinates (34) of 43 to 73% enantiomeric purity in 50 to 84% yield. This made available sulfinate esters for the synthesis of t-butyl sulfoxides (35). 

Although the exact mechanism of the reaction is difficult to resolve, from our accumulated data we can propose a mechanism which explains the experimental results obtained and enables the prediction of the stereochemistry of the sulfinate formed, based on the steric volume of the amine. The experimental data clearly demonstrate that the diastereoselective formation of a sulfinate is base-dependent. Therefore, the proposed mechanism has to include the effect of the base on the stereocourse of the reaction. Some additional circumstances have to be taken into account (1) the reaction of sulfiny 1 chlorides with alcohols in the presence of bases does not proceed via a sulfine intermediate117 (2) Mislow has proved that the reaction of chiral alcohols with sulfinyl chlorides in the presence of a base is kinetically controlled814,83 and (3) on first inspection, one could imagine the extreme case where DAG, under the influence of the base, reacts with only one of the enantiomeric sulfinyl chlorides. However, this is not the case, because the same yield and ee are obtained when 1.2 or 2.0 equiv of MeSOCl are used. Accordingly, the first step of the process could be an equilibrium reaction involving the sulfinyl chloride and the base. The racemic sulfinamide formed would be the active sulfur species that interacts with the sugar derivative. 

In this chapter, we attempt to review the current state of the art in the applications of cinchona alkaloids and their derivatives as chiral organocatalysts in these research fields. In the first section, the results obtained using the cinchona-catalyzed desymmetrization of different types of weso-compounds, such as weso-cyclic anhydrides, meso-diols, meso-endoperoxides, weso-phospholene derivatives, and prochiral ketones, as depicted in Scheme 11.1, are reviewed. Then, the cinchona-catalyzed (dynamic) kinetic resolution of racemic anhydrides, azlactones and sulfinyl chlorides affording enantioenriched a-hydroxy esters, and N-protected a-amino esters and sulftnates, respectively, is discussed (Schemes 11.2 and 11.3). 

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