Sulfenes dimerization reactions

Acyl sulfenes, like all sulfenes, prefer to participate as 2ir components of [2 -I- 2] or [4 + 2] cycloadditions (Chapter 5). Nonetheless, a range of [4 -I- 2] cycloaddition reactions of acyl sulfenes have been described - (Scheme 8-XII), including their 47t participation in dimerization reactions and reactions with imines, carbodiimides, ketenimines, 1-azirines, vinyl ethers,and ketenes. The reactions often provide mixtures of [4 + 2] and [2 + 2] cycloadducts, and the observed course of the reaction usually depends on the reaction conditions. Consequently, many of the observed [4 + 2] cycloadditions of acyl sulfenes proceed by a stepwise, polar addition-cyclization reaction. 

The reaction of thiirane 1-oxides with water or methanol is usually acid-catalyzed and gives /3-substituted sulfenic acids which dimerize to thiolsulfinates (54 Scheme 70) (72JA5786). If acetic acid is used a mixture of disulfide (55) and thiolsulfonate (56) is obtained. Treatment of thiirane 1,1-dioxides with hydroxide ion may involve attack on carbon as well as on sulfur as exemplified by 2-phenylthiirane 1,1-dioxide (Scheme 71). 

Closely related is the reaction of tertiary amines with sulfonyl halides that contain an a hydrogen. In this case, the initial product is the highly reactive sulfene, which cannot be isolated but reacts further to give products, one of which may be the alkene that is the dimer of RCH. Reactions of sulfenes in situ are also common (e.g., see 16-62). 

Sulfenes derived from a-halome.thanesulfonyl chlorides undergo reactions with quinuclidine (used as dehydrochlorinating agent) in markedly different manners as the halogen changes from bromine to fluorine [160]. The ability of a bromine atom to assume an acceptor role which is coerced by the sulfur atom (a-d-a sequence) is responsible for the formation of a dimer . On the other hand, a fluorine atom imposes its neighbor the acceptor role. 

On treatment with weak base, 1,3-oxathiolane sulfoxide (80) was shown to undergo a reversible intramolecular ene reaction to sulfenic acid (81). Using stronger base, it was found that this pericyclic reaction cannot compete with elimination to enone (82), which then oxidizes or dimerizes to the observed products (83) and (84). The diastere-omeric sulfoxide (79) was found to undergo retro-ene elimination then dimerization to (85) or to (83) and (84) with even a weak base.85... 

Another simple elimination reaction on the thiosulfinate ester makes another molecule of the sulfenic acid and a highly unstable unsaturated thioaldehyde, which promptly dimerizes to give a thioacetal found in garlic as a potent platelet aggregation inhibitor. 

The answer to all these questions is found in the demonstration (37) that the monomeric, unstable, lachrymatory compound produced by onions is not 1-propenylsulfenic acid, the presumed precursor of the dimer, but, as suggested a decade earlier (38), thiopropionaldehyde-S-oxide (CH CHoCHSO). The mass spectographic evidence which suggested the sulfenic acid structure (22) for this product is consistent with the latter structure. The nuclear magnetic resonance and infrared spectral evidence are consistent only with it. A hypothesis uniting all the evidence is that the true product of the enzymatic reaction is the sulfenic acid, as... 

When 2-alkylsulfinyl-, 2-arylsulfinyl-, and 1,2-aralkylsulfinyl-benzimidazoles react with thiols, the unsymmetrical disulfides are obtained (instead of the symmetrical ones), together with ipso-substitution products. The reaction is believed to be initiated by protonation of the benzimidazole nitrogen. The sulfenic acid is then eliminated after the ipso-substitution by thiolate. The sulfonic acid, once formed, is so unstable that it reacts immediately with thiol or dimerizes to form thio-sulfinates from which the unsymmetrical disulfides are derived (Equation (56)) <87JOC4620>. 

A notable chemical feature reported by Sundermeyer in this work is the carbophilic addition to fluorosulfene to give the sulfino-betaine (60)11 as in equation 48. This is evidently a particularly simple illustration of carbophilic (alias abnormal or inverse ) addition to a sulfene, which is discussed more fully in Section V.A.3. This reaction is to be contrasted with that observed by the same authors with the chlorinated152 analogue and related species149, which presumably proceeds by normal thiophilic addition to form the unstable primary adduct (54, R = H, R = C1, Nu = NMe3), which on reaction with another sulfene molecule followed by a proton shift gives the more usual dimeric adduct 61 (equation 49). The reasons why 60 rather than 54 is produced from fluorosulfene may be complex, but the observation is consistent with the usual deactivating effect of a-fluoro (and a-alkoxy) substituents in carbanion formation (at sp2 hybridized carbons)153. 

The reaction of sulfene with certain pyridines has been found by Grossert163,164 to form the unusual heterocyclic system 70, perhaps by simple cyclization of 71, the pyridine analogue of 64 (equation 51). 2,6-Dimethoxypyridine, in which direct bonding to the nitrogen may be inhibited by the methoxy groups, undergoes what is postulated to be electrophilic attack by sulfene or its dimer to form, ultimately, the 3-substituted product... 

The reduction of the disulfide dication (36) to the disulfide can be achieved upon treatment with two equivalents of KI or Bu 4N I . However, treatment with KBr followed by aqueous workup gives acyclic dimers. The reaction mechanism outlined in Scheme 14 shows the formation of sulfenyl bromide (46) which is hydrolyzed into the sulfenic acid (47) which in turn dimerizes into the thiosulfinate intermediate. 

In contrast to the sulfenes, the [2-1-2] cycloaddition reactions of sulfines are not well known. The dimerization of ethylsulfine gives rise to a four-membered ring rra 5-3,4-diethyl-l,2-dithietane 1,1-dioxide, which is not the result of a [2-1-2] cycloaddition Similarly, reaction... 

In the reaction of benzoylmethanesulfonyl chloride with triethylamine the a-oxo sulfene 4 is generated, which undergoes dimerization via a [4+2] cycloaddition reaction to give the cyclodimer 5. 

The aforementioned heterocyclic building blocks possess the potential for exploring numerous reaction pathways [9]. Hence, Cossy et al. highlighted a-alkylation of various sultones 8 in the presence of n-butyllithium followed by the addition of different alkyl halides (Scheme 4.3) [5]. The choice of base was also found to be crucial, as the use of LDA resulted in the formation of a sulfene intermediate, which rapidly dimerized to product 10 through a [2+2]-cycloaddition. 

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