Sulfine, cycloaddition

Sulfines (RR C=S=0) are another type of thiocumulene and recently it has been demonstrated that they can participate in 1,3-dipolar cycloaddition... 

Cycloadditions to a cyano group are comparatively rare. The high-temperature reactions of 1,3-dienes, e.g. butadiene, isoprene and 2-chloro-l,3-butadiene, with dicyanogen, propionitrile or benzonitrile result in formation of pyridines (equation 80)70. Sulfonyl cyanides 147, obtained by the action of cyanogen chloride on sodium salts of sulfinic acids, add to dienes to give dihydropyridines 148, which are transformed into pyridines 149 by oxidation (equation 81)71. 

A 1,2,5-oxathiazoline 2-oxide is obtained by 1,3-cycloaddition of benzonitrile oxide to bis(trifluoromethyl)sulfine (115) (Equation (18)) <88CB75> (see Section 4.11.10). 

Oxathiazoles are produced from sulfines in 1,3-cycloaddition reactions with nitrones <84CHEC-I(6)934>. With nitrile oxides only those sulfines which have sufficiently strong electron-withdrawing substituents such as CF3 (115) display the desired regioselectivity otherwise 1,3-... 

Simple unsaturated sulfides cannot be used in place of enamines in cycloaddition reactions with sulfines leading to thietane dioxide derivatives. " Alkyl, vinyl, and cycloalkylvinyl sulfides, which carry a C=C double bond, are considerably less nucleophilic than the enamines and thus do not partake in cycloadditions to sulfene. But when the more electrophilic methylsulfonyl sulfene is used in association with an unsaturated sulfide substituted with a strong electron donating alkylamino group, the formation of thietane dioxides 72 is successful. 

Pyrazino sulfolenes 495 have been derived from a cycloaddition reaction of intermediate 494 with SO2. This intermediate is produced by the thermal decomposition of the sulfine 493 (Scheme 39) <2000JOC3395>. 

The reaction of photogenerated singlet oxygen with 2,5-dimethylthiophene results in ring opening (70TL791, 70TL795) the c/s-sulfine (149) and the rrans-diketone (150) are the main products. The mechanism of this reaction has been speculated upon. Since (149) itself is photoinert, the two products must arise by different pathways. The key intermediate is (148), formed by cycloaddition of the thiophene with 02 this can lead to the two observed products as shown in Scheme 28. An alternative pathway for the sulfine would be by attack of 02 on sulfur to yield (151), followed by the transformations shown. 

Both sulfines and sulfenes are readily involved in cycloaddition reactions [176,187]. 

There are only a few reported members of this series. The first mentioned is 3,4,5,6-tetrahydro-3-phenyl-2//-l,2,3-thiadiazine 1,1-dioxide, which is prepared in low yield by cyclization of N-3-chloropropylsulfonyl-N -phenylhydrazine with base (62JPR56). The well-known property of azoalkenes to undergo [4 + 2] cycloaddition reactions with dienophiles can be exploited to give 1,2,3-thiadiazines. Thus, N-phenylazostilbene, PhCH=C(Ph)N=NPh, reacts slowly with sulfine 1 at room temperature to yield the trans (44%) and cis (13%) isomers 2 and 3... 

The first unequivocal 1,3-dipolar cycloaddition of sulfines involves the reaction of 2,2,4,4-tetramethyl-3-thioxocyclobutanone S-oxide with diaryl thioketones to produce... 

The thermolysis of heteroaryl-substituted phenacyl sulfoxides 444 generates the sulfine PhC0CH=S=0 and cycloaddition to butadiene gives dihydrothiopyran 1-oxides. The normal formation of the cis adduct appears to be controlled by the elimination of the heterocyclic unit during sulfine formation. However, the presence of an external base both accelerates the reaction and leads to an increase in the trans product (Equation 136) <1999JOC6730>. 

Thiocarbonyl oxides are a subject of active investigation. The natural occurrence of sulfines and related compounds in plants of the genus Allium (onion, garlic, etc.) is included in a superb and extensive review by Block [91]. Two detailed papers [92, 93] report the isolation of zwiebelanes from onions and their chemical synthesis involving intermediate sulfines produced by oxidation of di-l-propenyl disulfide, subsequent sulfoxide accelerated [3.3] sigmatropic shift and the [2+2] cycloaddition of the C=S and C=S=0 moieties. A further article [94] provides a great deal of information on the mechanism of formation of (Z)-propanethial S-oxide, the lachrymatory factor of the onion, as well as its chemical synthesis and reactions. Techniques of analysis of the volatiles of onions have been further improved [95]. 

Thioaldehyde S-oxides behave as dienophiles with 1,3-dienes [241]. Cycloaddition involves the carbon-sulfur double bond of the heterocumulene to furnish dihydro-2H-thiapyran S-oxides (Table 6, entry 1). The cis trans product ratio was found to depend upon the initial diene/sulfine ratio. A large excess of diene selectively provided the cis cycloadducts, as a result of a stereospecific reaction of the (Z) sulfine. With a produced proportion of diene, mixtures of cis trans isomers are obtained, with a preference for the cis compound. The Italian authors have demonstrated that the slower reaction allows a (Z) to (E) isomerisation of the sulfines prior to addition. 

A cyanosulfine [242] and an oxosulfine [162] were trapped with 2,3-dimethyl-1,3-butadiene (Table 6, entries 2 and 3). Capozzi and his group have extended their phthalimido-sulfenyl chemistry to the synthesis of a-oxosulfines, and have observed a dichotomic behaviour towards cycloaddition. With 1,3-dienes, these sulfines act [243, 244] as dienophiles through their C=S bond (Table 6, entry 4) to afford dihydro-2H-thiapyran S-oxides. With alkenes (Table 7), such as 2,3-dimethyl-2-butene (entry 1) or vinyl-ethers (entry 2), they behave as dienes to give dihydro-1,4-oxathiin S-oxides [243-245]. 

Cycloaddition reactions of thioaldehydes and sulfines are most probably encountered in plants, as elegantly and soundly shown by the group of Eric Block during their investigation of sulfur products occurring in the Allium species (for a review see [91]). They were able [92, 93] to isolate bicyclic dithioacetal oxides, called zwiebelanes, and also to synthesise them from a thioxosulfine, already described in this review (Sect. 2.6, Scheme 18). An extremely rich stereochemical and analytical study has resulted. 

The isomers of the now very popular dioxiranes, carbonyl oxides, are much less well-known species. However, the reaction of both isomers with two aliphatic thioketones was investigated [258]. A clear cut difference in reactivity was observed, with dioxiranes leading expectedly to the sulfines, while 5-membered ring thio-ozonides were produced from the reactions with carbonyl oxides, thus proving the possibility of a dipolar cycloaddition. 

A precursor of a thiocarbonyl ylid, a dihydrothiadiazole, was reacted [259] with a sulfine, thiobenzophenone S-oxide, to lead mainly to a dithiolane S-oxide, the formation of which was rationalised through a 1,3-dipolar cycloaddition of the ylid with the C=S bond of the sulfine. It is interesting to note that an opposite regioselectivity was observed for thiofluorenone S-oxide. 

Huisgen et al. have reported [260] evidence for sulfines playing the role of dipole in [3+2] cycloaddition. The reaction of thiobenzophenones with the S-oxide of a cyclobutanethione proceeds at room temperature to yield crystals of 1,2,4-oxadithiolanes, in a process in which reversibility was demonstrated. 

The reaction of 2-diazopropane with geometrical isomers of different types of sulfines yields A3-l,3,4-thiadiazoline 1-oxides as the single product by a concerted regiospecific cycloaddition process. Introduction of bulky substituents in either of the reactants will sterically hinder the cyclization to a five-membered ring, and give rise to non-stereospecific formation of episulfoxides (Scheme 26) (73TL3589). 

An important type of SO2 interaction with metal complexes results in conversion of metal-carbon bonds to O- or S-sulfinates. This type of reaction is usually referred to as an insertion , although (as will be discussed below) the mechanism almost certainly does not involve conventional insertion into the M-C bond. The area has been investigated intensively, and we refer the reader to excellent reviews of the topic. We shall limit ourselves to a few illustrative examples with d- and f-element complexes and also mention some interesting cycloaddition and rearrangement reactions of transition metal unsaturated hydrocarbon complexes with SO2. 

At room temperature the zwitterionic intermediates readily convert to S-sulfinates, in some cases with concomitant formation of the cycloaddition side product CpFe(C0)2(CHCH2S(0)2tH2). 

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