Mechanism of sulfonamide cleavage by arene anion radicals

Abstract

In the cleavage of sulfonamides of secondary amines with arene anion radicals 2 moles of the reducing species are consumed rapidly, resulting in formation of amide and sulfinate anions. In the case of arenesulfinate ion a subsequent, much slower reduction converts this to arene hydrocarbon and a mixture of thiosulfate, sulfite, and sulfide salts. By analysis of competitive reactions, the rate law for the first step has been deduced as rate = ¿[anion radical][sulfonamide]. In the reaction of sodium naphthalenide (and probably sodium biphenylide) with the toluenesulfonamide of p-toluidine, electron transfer and cleavage are considerably faster than acid-base reaction with the acidic proton. Sodium anthracenide, however, reacts only as a base with this substrate. Gross structural effects on the scope of the reaction are discussed. The discovery of the efficient cleavage of arenesul-fonamides1 2 and toluenesulfonate esters3 with the anion radicals derived from aromatic hydrocarbons by treatment with alkali metals in ether solvents has prompted us to examine the mechanisms of these potentially useful reactions. Some results and conclusions concerning the anion radical cleavage of sulfonamides are presented in this paper.Preliminary examination of the reaction of several sulfonamides with sodium naphthalenide at room temperature in 1,2-dimethoxyethane (DME) indicated a rather variable stoichiometry. One equivalent of sul-(1) (a)

The Detosylation of Chiral 1,2-Bis(tosylamides)

“…N,N′-((2R,3R)-1,4-Di(piperidin-1-yl)butane-2,3-diyl)bis(N-ethyl-4methylbenzenesulfonamide) (15). In a similar modification as that for 4, 20 equiv of piperidine (0.13 mL, 1.3 mmol) was added in one portion to a solution of (R,R)-biaziridine (R,R)-1 (25 mg, 0.064 mmol) in DMF (0.5 mL), and the reaction mixture was stirred for 24 h. The reaction was quenched with H 2 O (10 mL), and the mixture was extracted with EtOAc (20 mL).…”

“…Initial attempts at deprotection started with 1,2-bis­(tosylamide) 2 using the standard SET reductant Mg/MeOH, which resulted in complete decomposition upon sonication (45 min). Further attempts at 1,2-(bistosylamide) deprotection using a variety of conditions commonly employed for monotosylamides, ,,− (SmI 2 , ,− Na/naphthalene, Mg/MeOH, , and Li/amine; see Table S1 in the Supporting Information for data) also resulted in decomposition or the return of the starting material and did not allow for the deprotection of the tosyl moiety regardless of the substrate scaffold (Scheme , X = O, N, CH 2 ). Only 1,2-bis­(tosylamide) 6 was capable of deprotection (Scheme ), with the corresponding diamine isolated in a modest yield (30%).…”

On the mechanism of cleavage of aryl alkanesulfonates by electron donors

“…In our studies of the reaction of sulfonyl derivatives with electron donors we have discovered two rather different types of mechanisms of cleavage. With arenesulfonamides (1) the initial electron-transfer step is rate controlling and results in S-N cleavage exclusively.2 This is followed by rapid further reduction resulting in formation of sulfinate and amide anions (eq l).3 With alkyl alkanesulfonates (2) ArSOzNR, ArS02-;' + NR,7" -1* ArSOr + NR," (l)8 1 R0S02R' -l-2•' -*-R• + R'SOr (5)» initial electron transfer results in a metastable substrate anion radical (2•-) which, if nothing further transpires, undergoes C-O cleavage yielding alkyl radical and sulfonate anion (eq 2).4 If, however, the concentration and/or reducing power of the electron donor is high enough, another electron is transferred and a different mode of cleavage, S-O, occurs (eq 3).4 Recently, we have observed a slightly different version of this latter mechanism in the electron transfer reactions of aryl phosphates (3). 5 Here, the initial substrate anion radical (3•-) undergoes P-O cleavage (eq 4), but if further reduced cleaves at the C-O bond (eq 5).…”

Synthesis of Bisubstrate Inhibitors of Porphobilinogen Synthase from Pseudomonas aeruginosa

“…The protection of the oxo groups with 1,2-bis(trimethylsilyloxy)ethane afforded 16. The deprotection of the amine with the sodium naphthalenide [27] [28] gave 17. The final step to obtain the desired compound 8 was the deprotection of the oxo groups.…”