Sulfoxides allylic

Sulfenyl chlondes react with allyl alcohols to yield allyl sulfenates, whtch are in equihbnum with the allyl sulfoxides [12] (equation 9a) These products can be oxidized to the corresponding sulfones (equation 9b) Pyrolysis of the sulfoxides gives sulfines or evidence for the presence of sulfmes Pyrolysis of sulfones leads to unsamrated compounds by extrusion of sulfur dioxide [12] (equation 9c)... 

However, it can be expected that anions of allyl sulfoxides maintain, at low temperature, the chiral integrity of the sulfoxide group and that reactions with electrophiles could have regio-and stereochemical implications. 

The reaction of the anion of an aryl allyl sulfoxide with benzaldehyde can take place via an a or y attack. The a attack leads to a product with three stercogcnic centers (four possible diastereomers) whereas the y attack results in a product which has only two stereogenie centers and geometric isomerism is possible. 

The stereochemical outcome of Lhese reaetions has been rationalized as arising from a tram-decalyl -like transition state completely analogous to that described in Section 1.5.2.2.3.2. for allylic sulfoxide anions1. 

While the chemistry of alkyl and allylic sulfoxide anions is similar to that of phosphine oxides, phosphinates and sulfone stabilized anions (Sections 1.5.2.2.1 -2), the situation is further complicated by the additional stereogenic center at sulfur. Therefore in all cases, asymmetric induction may arise from the stereocenter at sulfur. 

Addition of racemic allylic sulfoxide anions to 2(5//)-furanone gives y-1,4-addition adducts1. The simple and induced diastereoselectivities are completely analogous to that of 2-cyclopen-tenone described earlier. 

The enantiomerically pure isobomeol allyl sulfoxide derivatives (17 ,2Y,3/ ,4S )-1,7,7-tri-methyl-3-[(S)- or -(/ )-2-propenylsulfmyl]bicyclo[2.2.1]heptan-2-ol are thermally more stable inversion of configuration at sulfur, S -> / , occurs at 135-145 °C. Their lithio derivatives give exclusively y-1,4-adducts with 2-cyclopentenone19. 

Extension of these studies to the more sterically demanding allylic sulfoxide anion derived from T(/e/7-butylsulfinyl)-l-(2-methylpropyl)-2-butene on reaction with 2-cyclopentenone gave three diastcrcomcric 1,4-adducts, 3-[3-(7( rt-butylsulfinyl)-l, 5-dime thy lhexyl]cyclopentanones, in a ratio of 31 26 4333. 

The addition of the anions of racemic cyclic allylic sulfoxides to various substituted 2-cyclopentenones gives y-l,4-adducts as single diastereomeric products22. The modest yields were due to competing proton-transfer reactions between the anion and enone. The stereochemical sense of these reactions is identical to that for the 1,4-addition reaction of (Z)-l-(/erf-butylsulfinyl)-2-methyl-2-butene to 2-cyclopentenone described earlier. 

From studies on the addition of racemic allylic sulfoxide anions of 3-substituted l-(phenyl-sulfinyl)-2-propenes to racemic 4-tcrr-butoxy-2-cyclopentenone, it was found that (El-allylic sulfoxides give. vyw-products, and (Z)-allylic sulfoxides give anti-productsx. 

Sulfoxides (R1—SO—R2), which are tricoordinate sulfur compounds, are chiral when R1 and R2 are different, and a-sulfmyl carbanions derived from optically active sulfoxides are known to retain the chirality. Therefore, these chiral carbanions usually give products which are rich in one diastereomer upon treatment with some prochiral reagents. Thus, optically active sulfoxides have been used as versatile reagents for asymmetric syntheses of many naturally occurring products116, since optically active a-sulfinyl carbanions can cause asymmetric induction in the C—C bond formation due to their close vicinity. In the following four subsections various reactions of a-sulfinyl carbanions are described (A) alkylation and acylation, (B) addition to unsaturated bonds such as C=0, C=N or C= N, (C) nucleophilic addition to a, /5-unsaturated sulfoxides, and (D) reactions of allylic sulfoxides. 

The observations of the interconversion of allylic sulfenates and sulfoxides made by Braverman and Stabinsky34-38 are confirmed by the work of Mislow and coworkers44-47 who approached the problem from a different angle, namely, enhanced racemization of optically active allylic sulfoxides. 

Owing to the reversible nature of the allylic sulfenate/allylic sulfoxide interconversion, the stereochemical outcome of both processes is treated below in an integrated manner. However, before beginning the discussion of this subject it is important to point out that although the allylic sulfoxide-sulfenate rearrangement is reversible, and although the sulfenate ester is usually in low equilibrium concentration with the isomeric sulfoxide, desulfurization of the sulfenate by thiophilic interception using various nucleophiles, such as thiophenoxide or secondary amines, removes it from equilibrium, and provides a useful route to allylic alcohols (equation 11). 

One of the first uses of the allylic sulfoxide-sulfenate interconversion was made by Jones and coworkers64, who reported exclusive suprafacial rearrangement of the allyl group in the steroidal sulfoxide 17 shown in equation 13. Two other examples are shown in equations 1465 and 1566. Evans and coworkers have demonstrated the utility of the suprafacial allylic sulfoxide-sulfenate rearrangement in a new synthesis of the tetracyclic alcohol 24 (equation 16)67, as well as in a synthesis of prostaglandin intermediates as shown in equation 1768. The stereospecific rearrangement of the unstable sulfenate intermediate obtained from the cis diol 25 indicates the suprafacial nature of this process. 

In contrast to these results, a preference for rearrangement through an exo-transition state has been detected in the rearrangement of several cyclic allylic sulfoxides. For example, while sulfoxide 36 rearranged to alcohol 37 with 60% ee, introduction of bulky substituents at the (i position of the ring enhanced the optical purity to 90%, as a result of further destabilization of the endo conformation (equation 21)82,84. 

The data presented demonstrate that allylic sulfoxides can provide an easy and highly stereoselective route to allylic alcohols taking advantage of the facility of the allylic sulfoxide-sulfenate [2,3]-sigmatropic rearrangement. This is of considerable synthetic utility, since a number of stereoselective and useful transformations of allylic alcohols and their derivatives have become available in recent years107-109. 

In addition to the synthetic applications related to the stereoselective or stereospecific syntheses of various systems, especially natural products, described in the previous subsection, a number of general synthetic uses of the reversible [2,3]-sigmatropic rearrangement of allylic sulfoxides are presented below. Several investigators110-113 have employed the allylic sulfenate-to-sulfoxide equilibrium in combination with the syn elimination of the latter as a method for the synthesis of conjugated dienes. For example, Reich and coworkers110,111 have reported a detailed study on the conversion of allylic alcohols to 1,3-dienes by sequential sulfenate sulfoxide rearrangement and syn elimination of the sulfoxide. This method of mild and efficient 1,4-dehydration of allylic alcohols has also been shown to proceed with overall cis stereochemistry in cyclic systems, as illustrated by equation 25. The reaction of trans-46 proceeds almost instantaneously at room temperature, while that of the cis-alcohol is much slower. This method has been subsequently applied for the synthesis of several natural products, such as the stereoselective transformation of the allylic alcohol 48 into the sex pheromone of the Red Bollworm Moth (49)112 and the conversion of isocodeine (50) into 6-demethoxythebaine (51)113. 

Recently, a simple and general synthetic method for the preparation of N-alkylisothioazolidines involving [2,3]-sigmatropic rearrangement of appropriately substituted allylic sulfoxides to corresponding sulfenates, followed by intramolecular substitution of the latter, has been described (equation 28)126. 

Further examples of the utility of the allylic sulfoxide-sulfenate interconversion in the construction of various biologically active natural products include intermediates such as the /Miydroxy-a-methylene-y-butyrolactones (e.g. 63)128 and tetrahydrochromanone derivative 64129. Interestingly, the facility and efficiency of this rearrangement has also attracted attention beyond the conventional boundaries of organic chemistry. Thus, a study on mechanism-based enzyme inactivation using an allyl sulfoxide-sulfenate rearrangement has also been published130 131. 

Apparently, the first report of a double [2,3]-sigmatropic rearrangement of an allylic sulfoxide was published by Gaoni132. This author observed that the 1,4-pentadienyl... 

Analogous with the rearrangement of allylic sulfoxides is the [2,3]-sigmatropic rearrangement of propargylic sulfoxides to allenic sulfenates. This process, which has been relatively little studied so far, appears to be the first step in the facile and quantitative rearrangement of sulfoxide 98 to the hemithioacetal 101 (equation 45)167. This reaction,... 

Baechler and coworkers204, have also studied the kinetics of the thermal isomerization of allylic sulfoxides and suggested a dissociative free radical mechanism. This process, depicted in equation 58, would account for the positive activation entropy, dramatic rate acceleration upon substitution at the a-allylic position, and relative insensitivity to changes in solvent polarity. Such a homolytic dissociative recombination process is also compatible with a similar study by Kwart and Benko204b employing heavy-atom kinetic isotope effects. 

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