Allylic sulfoxide-sulfenate

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. 

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. 

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. 

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 . 

Subsequently, Kametani and coworkers observed a similar allylic sulfoxide-sulfenate-sulfoxide rearrangement. These authors reported the exceptionally facile ringopening reaction of condensed cyclobutenes facilitated by arylsulfinyl carbanion substituents. For example, treatment of sulfoxide 68 with butyllithium in tetrahydrofuran at — 30°C for 10 min, followed by normal workup, results in the formation of product 71, which can be explained by the intervention of a double [2,3]-sigmatropic rearrangement of the initial product 69 via 70 (equation 32). A similar double [2,3]-sigmatropic rearrangement of 1,4-pentadienylic sulfoxides has also been reported by Sammes and coworkers. ... 

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 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-... 

Treatment of allyl p-tolyl sulfoxide with LDA followed by addition of HMPA (4.4 mol equiv.) and chiral 2-methylalkanal (3 mol equiv.) at -78 C gave a mixture of readily separable a- and y-adducts, where the a y regioisomer ratios are markedly higher than those obtained in Ae reaction with aromatic aldehydes. Exposure of the a-adduct to an excess of a thiophile (trimethyl phosphite or dimethylamine in MeOH) results in quenching of the allylic sulfoxide-sulfenate equilibrium and affords diastereoisomeric mixtures of the syn- and anti-diols (Scheme 18), for which some yields and product ratios are shown in Table 3. 

This transformation presumably proceeds with initial formation of allylic sulfilimine 55, which rearranges via an envelope-like transition state to sulfenamide 56 (cf. Scheme 1-XIII). Interestingly, NMR analysis showed that this [2,3]-sigmatropic rearrangement lies totally on the side of this sulfenamide, unlike the allylic sulfoxide-sulfenate ester system, which lies predominantly to the side of the sulfoxide. Similarly, C-3 epimeric dihydrothiazine imine 58 can be converted by an identical pathway to E-erythrp vicinal diamine 59 in an efficient and totally stereoselective manner [Eq. (28)]. 

Scheme 18.19 Structural scenarios for alkene diastereoface selectivity in allylic sulfoxide sulfenate rearrangement.

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