Sulfoxide-sulfenate rearrangement

Also, the isolation of benzil 160 as the only product in the thermolysis of thiirene oxide 18a at 130 °C was rationalized22 in terms of initial ring expansion (sulfoxide-sulfenate rearrangement) followed by rearrangement to monothiobenzil 159. The latter might be expected to undergo hydrolysis or air oxidation to give benzil 160 (equation 65). 

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. 

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. 

The photochemical behavior of a number of substituted derivatives of thiochroman-4-one 1-oxides has been examined by Still and coworkers192-194. These authors also report that rearrangement to cyclic sulfenates, with subsequent reaction by homolysis of the S—O bond, appears to be a particularly favorable process. For example, ultraviolet irradiation of a solution of 8-methylthiochroman-4-one 1-oxide (133) in benzene for 24h afforded a single crystalline product which was assigned the disulfide structure 134 (equation 54). More recently, Kobayashi and Mutai195 have also suggested a sulfoxide-sulfenate rearrangement for the photochemical conversion of 2,5-diphenyl-l,4-dithiin 1-oxide (135) to the 1,3-dithiole derivatives 136 and 137 (equation 55). 

The synthesis takes advantage of the well-documented sulfoxide - sulfenate rearrangement , as well as of its retro-process, leading to cyclization and formation of the desired four-membered ring sulfoxide system (i.e. 211, 212). A closely related ring enlargement is based on the reversibility of this rearrangement and has found wide use in penicillin chemistry . 

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 . 

On treatment with camphorsulfonic acid/pyridine, methyl ( )-1-[(.S )-4-mcthylphcnylsuirinyl]-2-alkenoates undergo, enantioselectively, a sequential prototropic shift and allylic sulfoxide/ sulfenate rearrangement to produce methyl (R,/f)-4-hydroxy-2-alkcnoates in 64- 72% optical purity63a. 

Allyl sulfoxide -> sulfenate rearrangement.2 A key step in a stereoselective first synthesis of withaferin A (3), a steroid antitumor agent, is the production of the desired A/B ring system by an allyl sulfoxide-> sulfenate rearrangement in the presence of trimethyl phosphite (equation I). 

The reagent converts aldehydes or ketones into oxygenated perhydrooxobenzofur-anes by a 1,6-conjugate addition followed by aldol-type cyclization. Remaining steps involve dehydration, oxidation to the sulfoxide, and allylic sulfoxide-sulfenate rearrangement.1... 

Zhou, Z.S., Flohr, A. and Hilvert, D. (1999) An antibody-catalyzed allylic sulfoxide—sulfenate rearrangement. 

A number of different methods have been used to synthesize racemic sulfinyl dienes. They involve oxidation of dienylthioethers [119], reactions of a-sulfinyl carbanions with different electrophiles [60, 120], sulfoxide-sulfenate rearrangements of propargylic sulfenates followed by isomerization of the resulting sulfinylallenes [121], and reactions of sulfolenes with Grignard reagents [122]. 

In 1988 Gibbs and Okamura [128] described the intramolecular Diels-Alder reaction of the non-racemic vinylallene 150 to afford the adduct 151 (as a mixture of epimers at sulfur) in a completely exo-selective manner, due to the topographical and steric arrangement of the starting vinylallene (Scheme 74). Compound 150 was obtained as a mixture of epimers at sulfur from the optically pure propargylic alcohol 149 (this transformation involved a sulfoxide-sulfenate rearrangement). Compound 151 was used to synthesize (-l-)-sterpurene. 

Vinyl sulfoxides have been used as synthetic equivalents of alkynes in reactions with diazoalkanes to prepare pyrazoles. The initially obtained adducts subsequently eliminate or rearrange the sulfoxide moiety to achieve pyrazoles lacking the sulfur function. Thus, the adducts resulting by reaction of CH2N2 with the sulfinylated double bond of allenyl sulfoxides 213 are transformed through a sulfoxide-sulfenate rearrangement into hydroxymethyl pyrazoles 214 [168], whereas those obtained by reaction with sulfinyl coumarins 215 suffered sulfinyl elimination into the pyrazoles 216 [169]. In both cases l,H-pyrazoles were obtained as a consequence of a final tautomerization step (Scheme 101). These studies were carried out on racemic sulfoxides. 

In a synthesis of (+)-pleuromutilin, only a 1 1 mixture of diastereomeric vinylic alcohols (86% yield) was obtained by addition of vinylmagnesium bromide to the precursor ketone. Equilibration of the easily separated undesired alcohol to a 1 1 mixture was achieved by a twofold sulfoxide - sulfenate rearrangement [C6H5SC1, then (EtO)3P in refluxing methanol] raising the overall yield of the desired diastereomer to 70% after two cycles81. 

In addition to the above-mentioned 1,3-chirality transfer, another mode of transferring centro chirality from one atom to the other is the S C transfer. This feature of the reaction has already been discussed by Mislow in his 1968 paper [40], where he delineates all important stereochemical aspects of [2,3]-sigmatropic rearrangements using the sulfoxide-sulfenate rearrangement as an example. For the sulfinate-sulfone rearrangement under consideration here, the work of Hiroi in the early 1980s should be mentioned (Scheme 16) [44,... 

A close relative of the previous tandem [3,3]-[3,3] sigmatropic rearrangement invokes its tandem [2,3H2,3] counterpart the allylic sulfoxide-sulfenate rearrangement. As a key step in the synthesis of 5-deoxyleukotriene D, Corey applied the sequence of transformations illustrated in Scheme 12. The anion of allylic sulfoxide (149) undergoes 1,2-addition to methyl 5-formylpentanoate followed by low temperature benzoylation. Upon wanning the reaction mixture to ambient temperature, a facile sulfox-... 

Allylic sulfoxides are tdso of interest mainly because of the possible sulfoxide/sulfenate rearrangement described by Mislow when he observed that allyl p-tolyl sulfoxide racemized in a temperature range... 

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