Enantiomeric dialkyl sulfoxide

Enantiomerically pure sulfoxides play an important role in asymmetric synthesis either as chiral building blocks or stereodirecting groups [156]. In the last years, metal- and enzyme-catalyzed asymmetric sulfoxidations have been developed for the preparation of optically active sulfoxides. Among the metal-catalyzed processes, the Kagan sulfoxidation [157] is the most efficient, in which the sulfide is enantioselectively oxidized by Ti(OzPr)4/tBuOOH in the presence of tartrate as chirality source. However, only alkyl aryl sulfides may be oxidized by this system in high enantiomeric excesses, and poor enantioselectivities were observed for dialkyl sulfides. 

Chiral sulfoxides are useful intermediates in asymmetric synthesis. A number of methods for their preparation were developed in the last decade. An interesting displacement of dimethylphosphonylmethyl moiety, a carbon leaving group, from sulfur by Grignard reagents was used to obtain enantiomerically purep-tolyl sulfoxides.3 4 Optically pure methyl 4-bromophenyl sulfinate was subjected to a one-pot sequence yielding unsymmetrical dialkyl sulfoxides in 60-97% yield and >98% ee. A simple one-pot synthesis of chiral sulfoxides from norephedrine-derived... 

Some dialkyl sulfoxides (86) were also separated into enantiomers by complexation with 10b. n-Butyl methyl sulfoxide (86a) and methyl -propyl sulfoxide (86d) were easily separated with 10a to give enantiomerically pure (-i-)-86a and (-)-86d, respectively, in good yields. However, 86b and 86f were poorly separated with 10b, and 86c and 86e did not form complexes with 10b [32]. 

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). 

Enantiopure 2,2,5,5-tetramethyl-3,4-hexanediol was prepared by Yamanoi and Imamoto [46]. A combination of Ti(0-i-Pr)4 with this diol (1 2) gives a chiral catalyst for sulfide oxidation with cumyl hydroperoxide in the presence of 4A molecular sieves in toluene. At -20°C p-tolyl methyl sulfoxide (95% ee) was obtained in 42% yield together with 40% sulfone, A kinetic resolution increased, to some extent, the enantiomeric excess of the product, that is, at lower conversion (20% yield) the enantiopurity of the resulting sulfoxide was only 40% ee. This catalytic system is ineffective for the enantioselective oxidation of dialkyl sulfides. 

Snyder s modification of the Wudl method is suitable for the synthesis of dialkyl and alkyl aryl sulfoxides in high ee. Both enantiomeric sulfoxides may be produced, either by reversing the order of organometallic displacement or by using the (IS, 2/ )-(+)-enantiomer of ephedrine, which is commercially available. Compared with... 

The typical S-oxidation with BVMOs allows the formation of chiral sulfoxides from organic sulfides. This oxidation has received much interest in organic chemistry due to its use in the synthesis of enantiomerically enriched materials as chiral auxiliaries or directly as biologically active ingredients. This reaction has been studied extensively with CHMO from Adnetohacter showing high enantioselectivi-ties in the sulfoxidation of alkyl aryl sulfides, disulfides, dialkyl sulfides, and cychc and acyclic 1,3-dithioacetals [90]. CHMO also catalyzes the enantioselective oxida-hon of organic cyclic sulfites to sulfates [91]. 

The chiral host 10b was effective for enantiomeric separations of alkyl aryl sul-foximines (89a-g). By complexation of rac-89b, rac-89d and rac-89e with 10b, (-)-89b (100% ee, 37%), (-)-89d (100% ee, 70%) and (-F)-89e (100% ee, 50%), respectively, were obtained in the optical and chemical yields indicated [35]. However, separation of rac-89a with 10b was not effective and (-)-89a of 35% ee was obtained in 45% yield after five recrystallizations of the complex of (-)-89a and 10b from benzene. 89c, 89f and 89g did not form complexes with 10b. These results show that the efficiency of the enantiomeric separation is highest when the alkyl group is methyl or ethyl and the aryl group is m-tolyl. Since this tendency is similar to that in the case of sulfoxide, the efficiency of the enantiomeric separation of 89 probably depends on the packing of 10b and 89 molecules in the crystalline lattice of their inclusion complex, as has been reported for the complex of 10b and (-f)-85c [32]. Although 10b did not form complexes with dialkyl sulfoximines (90), 8 formed complexes with some of them, and some were separated into enantiomers efficiently by the complexation. For example, by complexation of 8 with rac-90a and rac-90b in ether, (-)-90a (100% ee, 80%) and (-)-90b (100% ee, 88%), respectively, were finally obtained in the optical and chemical yields indicated [35]. 

In conclusion, Snyder and Benson s approach allows the synthesis of enantiomerically pure dialkyl and alkyl aryl sulfoxides in good yields and with excellent enantioselectivities. Both enantiomers are accessible by reversing the order of organometallic displacement or by employing the (15,2J )-(+)-ephedrine enantiomer. The only limitations are observed in the synthesis of t-butyl phenyl and aryl phenyl sulfoxides. However aryl phenyl sulfoxides are accessible by the Andersen procedure, and t-butyl phenyl sulfoxides by an approach to chiral sulfoxides developed by Kagan, described below. 

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