Menthyl sulfinate

Aryl- and alkyl-magnesium halides were the first reagents used to form sulfoxides from sulfinate ester 19 and related (— )-menthyl arenesulfinates (equations 564,665,758 and 866). Whereas optically pure esters produced the homochiral sulfoxides shown in equations (5), (6) and (7), the ester shown in equation (8) was an oily mixture of four diastereomers which led to formation of a meso sulfoxide and a d, l pair enriched in one enantiomer. A homochiral sulfoxide was obtained by fractional crystallization. 

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. 

Optically active vinyl sulfoxides 6 were also produced from the reaction of 1 (R=H) with(-)-(S)-menthyl sulfinate, via the intermediate formation with in-... 

Preparation of enantiomerically pure sulfinate esters has most often been accomplished by making menthyl esters of arenesulfinic acids, particularly of p-toluenesulfinic acid. This... 

The Andersen synthesis of chiral sulfoxides has also been extended to diastereomerically or enantiomerically pure arenesulfinamides, which on treatment with methyllithium give optically active methyl aryl sulfoxides (83,85). The use of menthyl sulfinates in the synthesis of sulfoxides has been exploited in the preparation of optically active sulfoxides 47 and 48, which are chiral by virtue of isotopic substitution, H- D (86), and (87), respectively. More recent... 

In addition to sulfimides, the nitrogen analogs of sulfinates and sulfinamides are chiral and have been obtained as optically active compounds. For instance, the synthesis of diastereomeric menthyl p-toluenesulfinimidoates 90 mentioned above was effected by Cram and his collaborators (18,137) on two ways. The first comprised the reaction of racemic A -tosyl-p-tolueneiminosulfinyl chloride 92 with menthol, followed by separation of the diastereomers of 90, whereas in the second method the reaction of the ester (->45 with chloramine T was utilized. 

Andersen (75,76), as well as Mislow (221), discovered that the ORD curves of alkyl aryl sulfoxides show a strong Cotton effect in the region below 250 nm. An extensive study by Mislow and his coworkers (47) led to the following empirical rules, correlating the sign of the Cotton effect with the absolute configurations of chiral dialkyl, alkyl aryl, and diaryl sulfoxides, as well as menthyl esters of aromatic sulfinic acids ... 

The ORD and CD curves of chiral sulfinamides derived from aromatic sulfinic acids show a strong Cotton effect centered at 240 to 256 nm (83). The position of this Cotton effect, its dependence on the solvent used, and the amplitude reveal a complete analogy with that observed in alkyl aryl sulfoxides and aromatic menthyl sulfin-ates. Thus, the positive sign of the Cotton effect observed in the ORD curves of dextrorotatory sulfinamides is indicative of the (5)-configuration around sulfur in these compounds. 

Hydrogen chloride was also found to catalyze the racemization of chiral sulfinates. Herbrandson and Dickerson (267) found that diastereomerically pure menthyl arenesulflnates undergo epimeriza-tion in nitrobenzene in the presence of hydrogen chloride and chloride ions. On the basis of kinetic studies they proposed a mecha-... 

Mislow and his co-workers (261) suggested, however, that epimeriza-tion of menthyl sulfinates occurs via either a sulfurane intermediate 221 or a sulfonium salt 222. 

The induced diastereoselectivity is determined by the chiral sulfinyl moiety of the substrate and not by the menthyl chirality, since a similar but opposed d.r. is obtained in sulfoxide 1 (and ee in the oxidized allenylsulfone 2) when the (-)-menthyl (S/ )-sulfinate is used rather than the ( — )-menthyl (SS)-sulfinate. The induced diastereoselectivity is fair to good, as deduced from the optical purity of the sulfones 2, however, inadvertent resolution of the diastereomers during the chromatographic separation of the allenic and acetylenic sulfoxides may have affected the figures. 

There is an inversion of configuration at sulfur during this reaction. Two major experimental problems with this approach were recently solved, allowing its application to large quantities14. Diastereomerically pure menthyl sulfinate was previously obtained by crystallization of a mixture of both diastereomers in about 30 40% yield. It is now possible to convert the diastereomeric mixture into one pure diaslereomer by sulfur epimerization in hydrochloric acid under such conditions that the less soluble isomer crystallizes, the overall yield is as high as 90%14. 

Thin layer chromatograms were obtained with silica gel as absorbent and ethyl acetate as developing solvent. The order of elution and Rf values of the major components are as follows menthyl sulfinate (0.65), menthol (0.59), sulfinyl ketal (0.30). 

The synthetic route to R(+)-MPTSO is outlined in Reaction 6. The experimental detail followed that of Boucher and Bosnich (39) and is a modification of literature methods (46, 41). Chlorination of the para-toluene sulfinate gives the sulfinyl chloride that was converted to the (—)menthyl sulfinates. This di-astereomer mixture was resolved by fractional crystallization, and the subsequent Grignard reaction, that is known to proceed by direct inversion at the sulfur (42),... 

A quite general method of access to optically pure sulfoxides is due to Andersen [96-98] a menthyl sulfinate ester is reacted with a Grignard reagent. Both enantiomers of menthyl p-toluenesulfinate are commercially available. A large-scale preparation of (-)-menthyl (S)-p-toluenesulfinate as well as that of (7 )-(+)-methyl p-tolyl sulfoxide is described [99] by Solladi et al. Other related approaches are presented and discussed in [86]. 

A new class of chiral sulfinyl transfer reagents, much more reactive towards Grignard reagents than the Andersen menthyl sulfinate ester, have been introduced by Evans [102] and reacted with a wide range of nucleophiles to afford chiral sulfoxides, sulfinate esters or sulfinamides efficiently. These reagents are shown below ... 

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