Reactions with sulphenes

For a recent discussion on the stereochemical aspects of the Diels-Alder reaction with vinyl sulphoxides see References 662, 663. It should be pointed out that vinyl sulphoxides can be considered in [2 + 4]-cycloadditions as acetylene synthons since the sulphinyl moiety may be removed from the product by sulphenic acid elimination. Paquette and coworkers took advantage of this fact in the synthesis of properly substituted anthracenes 562664, (equation 360). 

S-chloro-phosphinothiolates with phosphorus trichloride leads to desulphurization.65 The reaction of sulphenates with phosphines leads to deoxygenation,66 and not (as previously reported) to desulphurization. Even when the ion pair (52 R1 = R2 = Me, R3 = Bun) was generated from the sulphide (53), the reaction still led to... 

Schenone and coworkers have shown in a large number of papers that tertiary aminomethyleneketones react as heterodienes, e.g. with sulphene generated from aliphatic sulphonyl chlorides and triethylamine as a heterodienophile, to yield / -aminosultons in a Diels-Alder reaction. An early simple example is reported by Opitz270 (equation 199). 

Aminopenicillanic acid (8) was converted to 6(5)-bromopenicillanic acid by trapping of the diazo-intermediate with hydrogen bromide. Esterification of the dicyclohexylamine salt (93) with p-methoxybenzyl bromide, followed by oxidation, afforded the sulphoxide (94) in 60% yield from 6-APA. Elaboration of this sulphoxide to the disulphide (96) was effected by the procedure established by Kamiya et al. [98] the sulphenic acid (95), formed by heating the sulphoxide to reflux in toluene, was intercepted by reaction with 2-mercaptobenzothiazole to yield the disulphide (96). The latter was transformed by base-catalysed double bond isomerization to the conjugated ester disulphide (97) [95% yield from (94)]. Reductive formylation of disulphide (97) then provided the formylthio-derivative (98). Cyclization of the oxalimide (99), obtained by ozonolysis of... 

Enamines reaction with methanesulphonyl chloride and its homologues in the presence of triethylamine to yield thietane 1,1-dioxides. Thus 1-morphoIinocyclohexene gives a bicyclic thietane dioxide and 2-methyl-l-pyrrolidinopropene and other enamines derived from aliphatic aldehydes react analogously (equation 1). It is thought that the reactions proceed by way of the unisolable sulphene 1, which adds to the enamine double bond in a stepwise or concerted manner. This question has been much debated (for a critical discussion, see Reference 2, p. 3386) and will not be pursued here. It has been found that there is a lack of stereoselectivity in the addition of sulphene to the conformationally rigid enamines derived from 4-t-butylcyclohexanone . 

If no nucleophilic species are present when the sulphene is produced, then it undergoes reaction with itself to form a dimer and a tetramer, which yield sulphonic acids on work-up311, as shown in equation 64. 

A rather surprising reaction of sulphenes with cyclic nitrones has also been used to prepare a range of sulphonic acid salts (equation 65)312. 

Earlier, it was shown that sulphenes, formed by reaction of sulphonyl halides with a base, reacted with alcohols to give sulphonate esters. These same reactive intermediates have also been used for the formation of sultones, by reaction with carbonyl-containing compounds424-428, as shown in equation 98. If the carbonyl compound contains an a-... 

The reaction of a sulphonyl chloride with amines to produce a sulphonamide also occurs in the presence of a base305,307,482,483. In this case, it is well established that the reaction proceeds via a sulphene intermediate, as shown in equation 117. Using this method for the preparation, some novel sulphonamides may be obtained. Thus, the reaction of sulphene with phthalimide give iV-methylsulphonylphthalimide484,485, as shown in equation 118. Reaction of sulphene with pyridine leads to a novel cyclic... 

Sulphenes, generated by reaction with tertiary amines (see Sections II.A.2 and II.B.2), react with SchifFs bases to give /7-sultams258,259. In all cases so far, Z-sultams predominate in the product mixture so that Hirotoka and Kobayashi have suggested a concerted [tc2s + 7t2s] mechanism for the reaction (equation 205)259. 

Reactions.—Full details are now available" of the photochemical and thermal [1,3] phenylthio shifts of allyl phenyl sulphides [(73)- (74)]. Oxidation of such sulphides can lead to allyl alcohols through the known sulphoxide-sulphenate equilibrium with sulphenate trapping. 

The hydrolysis of sulphenyl halides is believed to form sulphenic acids (equation 22). These compounds, however, have never been isolated in this reaction rather thiolsulphinate esters are formed by fast reaction of sulphenic acids with sulphenyl halides (equation 23). 

Paquette et alf have shown that the well-known reaction of sulphenes with vinyl amines to form thietan dioxides is amenable to asymmetric induction. The reaction of the parent sulphene with electronegatively substituted carbonyl compounds can follow two courses (see Scheme 1),... 

The structure of benzoylsulphene presents the possibility of reaction by normal 1,2-addition involving the sulphene bond only, or 1,4-addition involving the carbonyl group as well. Reaction with benzylidene-n-propylamine (1 1 ratio of reactants) gave only the 1,4-adduct (88) but... 

Six membered Rings.— The cycloadducts (277) are formed in good yield by reaction of sulphene with open-chain enaminones bearing a phenyl group at the 2-position.The conversion of 2-chloro-oxirans to 6-membered heterocycles has been described. The reaction with bidentate nucleophiles is most interesting, leading to mixed heterocycles such as (278). Tropone also reacts with 2-mercapto-ethanol to give a 95 5 mixture of the cyclohepta[l,2-6]-l,4-oxathiins (279), which could be separated by h.p.l.c. 

Reactions of sulphenes with A A -disubstituted 2-methylprop-l-enylamines and l-(A -morpholino)propenes give largely the thermodynamically less stable c/J-adducts (10). The /ra/ij-adduct is the major product with alkylsulphenes, where the atom jS to the sulphonyl group cannot develop appreciable negative... 

In addition to the above examples involving nitrogen (in Group V of the Periodic Table), a phosphorane analogue of a 1,3-thiazetidine 1,1-dioxide has been suggested as an intermediate in the reaction of alkylidene- and arylidene-triphenylphosphoranes with sulphenes derived from alkanesulphonyl fluorides. ... 

Fluoro-2-pyridone is readily prepared by reaction of 5% fluorine in nitrogen and 2-trimethylsiloxypyridine in trichloro-fluoromethane at -78°C the pyridone is a selective fluorinating reagent. 5 The novel 3-substituted pyridine (4-3) is formed when 2,6-dimethoxypyridine (42) is treated with sulphene (CH2=S02)> Treatment of 3-mercapto-2-pyridinethione with triethylamine yields the 1, 6-diazathianthrene (44). 

Reactions of Sulphenic Acids.—In continuation of previous work, penicillin sulphenic acids have been trapped with vinyl ethers and keten acetals, " " with thiols, alkenes, and alkynes. A variety of products from thermolysis of N-benzyloxycarbonyl-L-(S-t-butyl)cysteinyl-L-valine methyl ester S-oxide must derive from an intermediate sulphenic acid, and isothiazolones and thiazinones formed from penicillin sulphoxides are also satisfactorily accounted for on the same basis. "... 

Thioamide vinylogues (100) have been reported to yield Diels-Alder adducts on treatment with substituted alkenes and sulphenes/ In the former case, the heterocyclic compounds (107) and/or (108) were produced, depending on the substituents. In the latter case, the unsubstituted sulphene afforded merely (109), whereas solely the de-aminated products (110) were formed in reactions with benzylsulphene. 3-Alkylthio-l-aryl-3-arylamino-2-propene-l-thiones (41) have been converted into 3-arylamino-1,2-oxazoles, 3-arylaminopyrazoles, and the quinoline derivatives (111) by treatment with hydroxylamine, hydrazine, and sulphuric acid, respectively. " The formation of 2-imino-2H-thiopyrans by spontaneous ring-closure of -mercaptovinyl-acrylonitriles (112) has been reported recently. ... 

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