Allyl sulfoxides, rearrangement

Allylic oxidation is carried out by addition of one equivalent of selenium dioxide. First Se02 will react with the alkene in a [4 + 2] cycloaddition reminiscent of the ene reaction. The initial product is an allylic selenic acid 40, which undergoes - like an allylic sulfoxide -allylic rearrangement to give an unstable intermediate, which decomposes rapidly to the allylic alcohol 42.16... 

The study by Baechler and coworkers31, cited above, also provided data on the (1,3)-allylic rearrangement in /J-methylallyl phenyl sulfoxide. Using the same approach as was used in reinterpreting the sulfone data, the activation energy is estimated to be 151 kj mol- and AfH°(PhSO) = 45kJmol-1. 

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. 

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 1,3-allylic rearrangement has also been observed with several cyclic sulfoxides. For example, the interesting thermal interconversion of the bicyclic stereoisomeric pair 141... 

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 . 

The allyl sulfoxide-allyl sulfenate rearrangement can be used to prepare allylic alcohols.275 The reaction is carried out in the presence of a reagent, such as phenylthi-olate or trimethyl phosphite, that reacts with the sulfenate to cleave the S—O bond. 

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. 

Another [2,3] sigmatropic rearrangement converts allylic sulfoxides to allylically rearranged alcohols by treatment with a thiophilic reagent such as trimethyl phosphite.539 In this... 

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. 

The next example makes more involved use of these [2,3]-sigmatropic allylic sulfoxide-allylic alcohol rearrangements. It comes from the work of Evans (he of the chiral auxiliary) who, in the early 1970s, first demonstrated the synthetic utility of allylic sulfoxides. Here he is using this chemistry to make precursors of the prostaglandins, a family of compounds that modulate hormone activity within the body. 

The initial product is an allylic seieninic acid—and just like an allylic sulfoxide (but more so because the C-Se bond is even weaker) it undergoes allylic rearrangement to give an unstable compound that rapidly decomposes to an allylic alcohol. In some cases, particularly this most useful oxidation of methyl groups, the oxidation continues to give an aldehyde or ketone. 

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