Reductive cleavage of sulfones and sulfonamides by a neutral organic super-electron-donor (S.E.D.) reagent.

The sulfonyl group finds extensive applications in organic and medicinal chemistry both in sulfonamides, popular as robust protecting groups for amines,1 and in sulfones.2 Frequently, sulfones are introduced into synthetic schemes to assist particular transformations; further progress along the synthetic route can later require the removal of a sulfone group, and this can be achieved by reductive desulfonylation2,3,6 or, in the special cases of R-haloor â-acyloxysulfones, by elimination to an alkene.2-5 For reductive removal of sulfones and for reductive cleavage of classic sulfonamides, different methods2,3 use alkali metals (Li, Na, K), lithium naphthalenide, SmI2 with HMPA, or LiAlH4 in the presence of nickel compounds. All these reduction methods are mediated by highly aggressive metal-containing reducing agents. Electrochemical reduction is also used for the reductive cleavage of aryl sulfones7 (ArSO2R) and sulfonamides.8 With typical reduction potentials of -2.3 V,8b they pose some of the greatest challenges in functional group reduction. In this paper, we report the first reductive cleavage of sulfones and sulfonamides with a neutral organic electron donor, operating in its ground state, a member of the family of reagents that were recently named the “super-electron-donor” reagents.9 These compounds are tetraazaalkenes that on oxidation afford radical cations and dications stabilized by aromaticity. We recently disclosed10 the ability of the super-electron-donor reagent bisbenzimidazolylidene 111 to reduce aryl iodides and alkyl iodides in excellent yields to the corresponding radicals. Although 1 is a powerful reducing agent,11,12 it was not powerful enough to reduce sulfones or sulfonamides. Accordingly, more powerful reducing agents were sought, and bisimidazolylidene 3 was selected.9,11 Compound 3 has previously been prepared11 by electrochemical reduction of the disalt 4; it shows a 2-electron wave [E1/2 (DMF)11a ) -1.20 V vs SCE] and thus 3 is a significantly better reducing agent than 1. We have very recently devised an easy preparation of 3 from 2 (Scheme 1),9 which, in turn, is simply formed from imidazole and diiodopropane. Although its organic chemistry had not previously been explored, we have shown9 that 3 is the first neutral organic molecule to form aryl anions from iodoarenes by double electron-transfer. To test the reactivity of donor 3, three monosulfones were now tested. Sulfone 5 underwent conversion to the alkene 8 in high yield (79%). Similarly, sulfone 6 was cleanly converted (97%) into hydrocarbon 9. However, the “unactivated” sulfone 7 afforded only starting material. This made it clear that reagent 3 would selectively cleave mildly activated sulfones. The most useful group of such sulfones are the gem-disulfones; such disulfones are widely used in synthesis.2 They are normally reductively cleaved with alkali metals1,2 to the corresponding monosulfone anions 20. Accordingly, we assayed 3 against disulfones 10-13. We were pleased to isolate excellent yields (94-98%) of the monosulfones 14-17 after workup and chromatography. The oxidation products of 3, that is, the corresponding radical-cation (not shown) and the dication 4, are water-soluble salts, allowing easy purification of products 1417. In these reactions, electron-transfer to the arenesulfonyl group affords the radical-anion 18 that could fragment to give either [radical 19 + anion 22] or [anion 20 + radical 21] (see later for further discussion). Transfer of a further electron under the reaction conditions should lead to the pair of anions 20 + 22. Confirmation of the presence of the anion 22 came from a repeat of the reduction experiment for substrate 11. At the end of the experiment iodomethane (excess) was added, affording phenyl methylsulfone, PhSO2Me 23 (86%). It is known that geminal disulfones are activated relative to monosulfones,8b and also that aryl allylsulfones and aryl benzylsulfones ArSO2CH2Ar′ undergo more facile cleavage than aryl alkylsulfones ArSO2R, but analysis of the nature of the activations Scheme 1. Preparation of Donor 3 and Reactions with Sulfones Published on Web 10/16/2007