Enantiomeric optically active sulfoxide

The earliest attempts to obtain optically active sulfoxides by the oxidation of sulfides using oxidants such as chiral peracids did not fare well. The enantiomeric purities obtained were very low. Biological oxidants offered great improvement in a few cases, but not in others. Lately, some very encouraging progress has been made using chiral oxaziridines and peroxometal complexes as oxidants. Newer developments in the use of both chemical oxidants and biological oxidants are described below. 

Table 11 Result of one-pot preparation method of optically active sulfoxides (64a-d) by a combination of oxidation of sulfide and enantiomeric ...

This chapter, however, does not deal with above-mentioned reactions of sulfoxides. Rather it is limited to asymmetric synthesis using a-sulfinyl carbanions and -unsaturated sulfoxides, specifically in which the stereogenic sulfoxide sulfur atom is enantiomerically pure. Therefore reactions of racemic sulfoxides are for the most part excluded from this review. For more general discussions, the reader is referred to other chapters in this volume and to other reviews on the chemistry of sulfoxides. Especially useful are the reviews by Johnson and Sharp and by Mislow in the late 1960s and by Oae and by Nudelman as well as a book by Block . A review by Cinquini, Cozzi and Montanari" through mid-1983 summarizes the chemistry and stereochemistry of optically active sulfoxides. This chapter emphasizes results reported from 1984 through mid-1986. 

In contrast to the situation with the Baeyer-Villiger oxidation, synthetic chemists have a choice of both enzymatic or non-enzymatic methods for the oxidation of sulfides to optically active sulfoxides with good to excellent yields and enantiomeric excesses. 

Since in principle the reactions of enantiomeric sulfoxides with a chiral reagent are expected to proceed at unequal rates, a possibility exists for obtaining chiral sulfoxides, especially when the reacting racemic sulfoxide is used in excess in relation to the chiral reagent. A typical example of such a kinetic resolution of a racemic sulfoxide is its reaction with a deficiency of chiral peracid, affording a mixture of optically active sulfoxide and achiral sulfone (62,63). However,... 

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... 

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. 

Finally, we would like to describe the enantiomeric separation of racemic methyl phenyl sulfoxide by the dipeptide (1). Optically active sulfoxides are utilized as a... 

Optically active sulfoxides can also be prepared by asymmetric oxidation of sulfides. However, numerous papers have reported very low enantioselectivity." Only one report, " using a modified Sharpless reagent, H20/Ti(0Pr )4/diethyl tartrate/BuKX)H, described asymmetric oxidation of alkyl aryl sulfoxides with good enantiomeric excesses 75 to 95%. 

The use of optically active sulfoxides for the synthesis of optically active alkenes has been reported, e.g. the (5)-sulfoxide (55) gave the (5)-alkene (56) on heating at 250 C (equation 27). However, the observed enantiomeric excesses were only modest and the reactions were only carried out to low conversions. 

Chiral (salen)oxovanadium complexes for sulfide oxidation were first investigated by Fujita [29,43]. In the presence of 4 mol % of the catalyst optically active sulfoxides were obtained in good yields, however, the enantiomeric excesses remained only moderate (up to 40%). 

Pummerer rearrangement of the optically active sulfoxide (64) to the 1,3-benzoxathiinone (65) occurs with moderate to good transfer of enantiomeric excess when the reaction is promoted by ethoxy vinyl esters <97TA303>. 

Table 3.3-7 Result of one-pot preparation of optically active sulfoxides 98a-d by a combination of sulfide oxidation and enantiomeric resolution in a water suspension medium.

Following the pioneering work of Gilman [1], Andersen, in 1962, reported the first synthesis of an optically active sulfoxide of high enantiomeric purity through nucleophilic displacement at sulfur [2]. The key step in Andersen s procedure... 

The facile racemization of optically active sulfoxides (enantiomerically enriched in configuration at sulfur) provided early evidence for the concerted, [2,3]-sigmatropic nature of the allylic sulfoxide-to-sulfenate rearrangement (Scheme 18.31. Mislow found that racemization occurred readily at 50-70 °C, conditions considerably milder than the 130-150 °C required for the radical-cleavage pathway associated with the corresponding benzyl sulfoxide and well below the tenperature needed for pyramidal inversion at the sulfoxide sulfur center (190-220 °C). 

Chiral chemical reagents can react with prochiral centers in achiral substances to give partially or completely enantiomerically pure product. An example of such processes is the preparation of optically active sulfoxides from achiral sulfides using a chiral oxidant. To convert a sulfide to an optically active sulfoxide, the reagent must preferentially react with one of the two prochiral faces of the sulfide. 

A chiral Ti complex formed in situ by reacting Ti(0 Pr)4, (J ,P)-diphenylethane-1,2-diol, and water was reported to be effective for asymmetric oxidation of aryl alkyl and aryl benzyl sulfides using TBHP as the oxidant to obtain optically active sulfoxides in good yields and high enantiomeric excesses [274] (Scheme 14.115). 

An asymmetric synthesis of estrone begins with an asymmetric Michael addition of lithium enolate (178) to the scalemic sulfoxide (179). Direct treatment of the cmde Michael adduct with y /i7-chloroperbenzoic acid to oxidize the sulfoxide to a sulfone, followed by reductive removal of the bromine affords (180, X = a and PH R = H) in over 90% yield. Similarly to the conversion of (175) to (176), base-catalyzed epimerization of (180) produces an 85% isolated yield of (181, X = /5H R = H). C8 and C14 of (181) have the same relative and absolute stereochemistry as that of the naturally occurring steroids. Methylation of (181) provides (182). A (CH2)2CuLi-induced reductive cleavage of sulfone (182) followed by stereoselective alkylation of the resultant enolate with an allyl bromide yields (183). Ozonolysis of (183) produces (184) (wherein the aldehydric oxygen is by isopropyUdene) in 68% yield. Compound (184) is the optically active form of Ziegler s intermediate (176), and is converted to (+)-estrone in 6.3% overall yield and >95% enantiomeric excess (200). 

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). 

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