Allyl sulfenate

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)... 

There are several reactions in which the sulfoxy oxygen exhibits its nucleophilicity, the most noticeable being the thermal rearrangement of thiirane oxides (in the presence of a suitable disposed /J-hydrogen) to allylic sulfenic acids2,63,105 (see equation 9 in Section III.C.l). 

Following studies on the rearrangement of allylic arenesulfinates, Braverman and coworkers have investigated a number of natural extensions of this unique transformation, including the predictable [2,3] sigma tropic rearrangements of allylic sulfenates to sulfoxides and of propargylic sulfenates and sulfinates to allenic sulfoxides and sulfones respectively. The last reaction is described below, while the other two are described in Chapter 14. 

B. The Reversible [2,3]-Sigmatropic Rearrangement of Allylic Sulfenates to Sulfoxides... 

Since its discovery two decades ago, the reversible interconversion of allylic sulfenates to sulfoxides has become one of the best known [2,3]-sigmatropic rearrangements. Certainly this is not only because of the considerable mechanistic and stereochemical interest involved, but also because of its remarkable synthetic utility as a key reaction in the stereospecific total synthesis of a variety of natural products such as steroids, prostaglandins, leukotrienes, etc. 

In contrast to the allylic sulfenates mentioned so far, cinnamyl trichloromethanesulfenate (9), prepared by the usual method, can be isolated and is relatively stable. Furthermore, its rearrangement to cinnamyl trichloromethyl sulfoxide (i.e., without allylic isomerization, equation 7), proceeds at a relatively slow rate (in CC14 at 80.0 °C, k = 3.90 x 10 5s 1). This result also contrasts with the observation mentioned earlier that cinnamyl arenesulfinate rearranges to a-phenylallyl aryl sulfone33,34. Similar behavior has been detected for y, y-dimethylallyl ester 11 which undergoes thermal isomerization to sulfoxide 12 (equation 8)36-38. 

In summary, the evidence described above demonstrates three main mechanistic features of the rearrangement of allylic sulfenates to sulfoxides (1) spontaneous and wholly concerted [2,3]-sigmatropic shift of allyl or a-substituted allyl esters (7 a, b) at one extreme (2) complete stability of the y-aryl and y,y-dialkyl substituted allyl sulfenates as well as... 

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). 

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. 

A similar intramolecular nucleophilic capture of an allylic sulfenate generated thermally from the corresponding sulfoxide was also reported for the facile transformation of the azetidinone 61 into a new 3-acetylthio-2-thiacephem ring system 62 (equation 29)127. 

In the presence of a suitably disposed /i-hydrogen—as in alkyl-substituted thiirane oxides such as 16c—an alternative, more facile pathway for thermal fragmentation is available . In such cases the thiirene oxides are thermally rearranged to the allylic sulfenic acid, 37, similarly to the thermolysis of larger cyclic and acyclic sulfoxides (see equation 9). In sharp contrast to this type of thiirane oxide, mono- and cis-disubstituted ones have no available hydrogen for abstraction and afford on thermolysis only olefins and sulfur monoxide . However, rapid thermolysis of thiirane oxides of type 16c at high temperatures (200-340 °C), rather than at room temperature or lower, afforded mixtures of cis- and trans-olefins with the concomitant extrusion of sulfur monoxide . The rationale proposed for all these observations is that thiirane oxides may thermally... 

The thermolysis of acyclic- and/or six- and larger ring sulfoxides to yield olefins and sulfenic acids is well documented . The formation of allylic sulfenic acids and thiosulfinates in the thermolysis of thiirane oxides containing hydrogen on the a-carbon of the ring substituent (which is syn to the S—O bond) has been discussed previously in terms of /i-elimination of hydrogen, which is facilitated by relief of strain in the three-membered ring (Section llI.C.l). 

An allylic sulfenate, like 199, is known to be in equilibrium with allylic sulfoxide, like 196, although its concentration is usually low . Various allylic sulfoxides can be prepared by treatment of allylic alcohols with arenesulfenyl chlorides . Evans and coworkers prepared various allylic alcohols by treating the corresponding allylic sulfoxides with trimethyl phosphite. For example, the carbanion from a cycloalkenyl sulfoxide 201 was readily alkylated at the a-position by treatment with alkyl halide. The resulting alkylated derivative 202 was then treated with trimethyl phosphite and 3-substituted cycloalkenol was obtained. Alkylation of acyclic allylic sulfoxide 204 gave... 

As a continuation to the studies by Darwish and Braverman on the [2,3]-sigmatropic rearrangement of allylic sulfinates to sulfones, and in view of its remarkable facility and stereospecificity (see Chapter 13), Braverman and Stabinsky investigated the predictable analogous rearrangement of allylic sulfenates to sulfoxides, namely the reverse rearrangement of that attempted by Cope and coworkers . These authors initiated their studies by the preparation of the claimed allyl trichloromethanesulfenate using the method of Sosnovsky . This method involves the reaction between trichloro-methanesulfenyl chloride and allyl alcohol in ether at 0 °C, in the presence of pyridine (equation 6). 

Although the interception of allylic sulfenates in the manner described by equation 11 was first observed by Abbott and Stirling ", the general value of this transformation and its remarkable synthetic potential has been recognized by Evans and coworkers , who have also introduced the previously used trimethyl phosphite as a preferable trapping agent. An early review of the synthetic utility of the reversible allylic sulfoxide-sulfenate rearrangement has also been published by Evans and Andrews . 

Deprotonation of allylic aryl sulfoxides leads to allylic carbanions which react with aldehyde electrophiles at the carbon atom a and also y to sulfur . With benzaldehyde at — 10 °C y-alkylation predominates , whereas with aliphatic aldehydes at — 78 °C in the presence of HMPA a-alkylation predominates . When the a-alkylated products, which themselves are allylic sulfoxides, undergo 2,3-sigmatropic rearrangement, the rearranged compounds (i.e., allylic sulfenate esters) can be trapped with thiophiles to produce overall ( )-l,4-dihydroxyalkenes (equation 24). When a-substituted aldehydes are used as electrophiles, formation of syn-diols 27 occurs in 40-67% yields with diastereoselectivities ranging from 2-28 1 (equation 24) . ... 

The rearrangement of allylic sulfoxides to allylic sulfenates was first studied in connection with the mechanism of racemization of allyl aryl sulfoxides.272 Although the allyl sulfoxide structure is strongly favored at equilibrium, rearrangement through the achiral allyl sulfenate provides a low-energy pathway for racemization. 

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