Sulfones, allyl radical cyclizations

On treatment with a radical generator, the 4-mercaptopentyl derivatives of vinylcyclopropanes 456 cyclize to a mixture of stereoisomers of tetrahydrothiopyran (Equation 146) <1993SL827> and a tetrahydrothiopyran 1,1-dioxide results from a 1,3-rearrangement prior to the radical cyclization of allylic pentenyl sulfones 457 (Equation 147) <1993TL2537>. 

Eliminations. Specially designed sulfones undergo elimination which is initiated by a remote radical. The alkyl moiety is converted to an alkene. The core of the squalene synthase inhibitor CP-225917 has been synthesized via a radical cyclization with ejection of an allylic phenylthio group. The radical precursor is an a-bromoacetic ester. 

Allyl sulfones offer the possibility to conduct cyclization reactions that are isomerizations, and investigations by Smith and Whitham indicate that this is a very promising technique for the preparation of functionalized products.118 The mechanism consists of reversible addition of a sulfonyl radical to a terminal alkene or alkyne, cyclization, and fragmentation of the resulting -sulfonyl radical. Two examples of these isomerizations are provided in Scheme 26. 

A chemoselective addition of allylic alcohols (82) to 3-halogenovinyl sulfones (81) has been accomplished using KF-basic alumina as the basic medium.55 The resulting adducts (83) can be stereoselectively cyclized by a radical process, affording 2,4-disubstituted tetrahydrofurans (84) (Scheme 22, Eq. 1). The same group has recently reported an analogous protocol using allylic amines (85) for the synthesis of 2,4-disubstituted pyrrolidines (87) (Scheme 22, Eq. 2)56... 

More complex products are obtained from cyclizations in which the oxidizable functionality and the alkene are present in the same molecule. y9-Keto esters have been used extensively for Mn(III)-based oxidative cyclizations and react with Mn(OAc)3 at room temperature or slightly above [4, 10, 11, 15], They may be cyclic or acyclic and may be a-unsubstituted or may contain an a-alkyl or chloro substituent. Cycloalkanones are formed if the unsaturated chain is attached to the ketone. y-Lactones are formed from allylic acetoacetates [10, 11]. Less acidic /3-keto amides have recently been used for the formation of lactams or cycloalkanones [37]. Malonic esters have also been widely used and form radicals at 60-80 °C. Cycloalkanes are formed if an unsaturated chain is attached to the a-position. y-Lactones are formed from allylic malonates [10, 11]. yff-Diketones have been used with some success for cyclizations to both alkenes and aromatic rings [10, 11]. Other acidic carbonyl compounds such as fi-keto acids, /3-keto sulfoxides, j8-keto sulfones, and P-nitro ketones have seen limited use [10, 11]. We have recently found that oxidative cyclizations of unsaturated ketones can be carried out in high yield in acetic acid at 80 °C if the ketone selectively enolizes to one side and the product cannot enolize... 

When one of the alkene units of the diene is replaced by an allyl sulfone moiety, cyclization may be initiated with a smaller than stoichiometric amount of the selenosulfonate, since displacement of a sulfonyl radical from the allyl sulfone group propagates the chain reaction (eq 18). A related procedure that leads to the cyclization of sulfonyl-suhstituted indoles is shown in eq 19. ... 

Examples of two C-C bond formation have also been reported. Thus, the addition of sulfone (12) to A-allyl, A-prenyl tosylamide affords the adduct (13) in 68% yield as a mixture of stereoisomers (equation (73)) [141]. The reaction mechanism has the following radical cascade sulfonyl radical addition to diene, 5-exo cyclization, intermolecular C-C bond formation by addition to allyl sulfone and ejection of sulfonyl radical. 

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