Sulfines 4+2 cycloaddition reactions

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>. 

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... 

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. 

Stereoselective Diels-Alder reactions have been performed variously, using chirally modified sulfines as dienophiles, chiral ynamines, SMP enamines, SMP acrylamides, and the in situ preparation of SMP A-acylnitroso dienophiles. The [2 + 2] cycloaddition reactions of chiral keteniminium salts obtained from SMP amides with alkenes have been studied. ... 

Sulfines, which are thiocaibonyl 5-oxides, have been used many times as heterodienophiles. As with thioaldehydes, the development of this field has been limited more by the availability of these often unstable species rather than by problems with the Diels-Alder chemistry. It should be noted that sulfines can exist as configurationally stable ( )- or (Z)-isomers and this stereochemistry can play a role in the outcome of the cycloaddition reactions. 

Vinyl sulfones can function as acetylene equivalents through the elimination of sulfinic acid. Reck and coworkers prepared a series of vinyl sulfones for cycloaddition reactions with azides to prepare 1,2,3-triazole derivatives to be incorporated into new oxazolidinone antibacterial agents. Included in the series was the cycloaddition of l-fluoro-l-(phenylsulfonyl)ethylene with the oxizolidinone 156 to give, after elimination of phenylsulfonic acid, a 28% yield of a 1 7 mixture of the regioisomeric 4-and 5-fluorotriazoles (157 and 158) (Fig. 3.91). 

Diels-Alder reactions. Heldeweg and Hogeveen have shown that, at least in the case of highly reactive dienes, the initial products of cycloaddition of sulfur dioxide are sulfinic esters rather than sulfones. Thus reaction of the tricyclic diene (1) with SO2 at room temperature leads to the sulfinic ester (2). This ester is unstable thermally and rearranges mainly to the aromatic ester (3). They also point out the similarity between cycloaddition reactions of sulfur dioxide and selenium dioxide. Thus (1) reacts with the latter reagent to give the seleninic ester (4), probably formed via the intermediate (a). 

The authors chose polystyrene/divinylbenzene sodium sulfinate resin as the solid support, as it easily grants access to the vinyl sulfone needed for the cycloaddition reaction. The sulfone was generated via a microwave-assisted reaction with a suitable benzyl halide bearing an electron-withdrawing group (Scheme 8.12). 

The chemical reactivity of the cumulenes under discussion ranges from highly reactive species to almost inert compounds. While some cumulenes can only be generated in a matrix at low temperatures, others are indefinitely stable at room temperature. For example, sulfines and sulfenes are only generated in situ, but some cumulenes with bulky substituents are sometimes isolated at room temperature for example, C=C=S was detected in interstellar space by microwave spectroscopy, and its spectrum was later verified by matrix isolation spectroscopy. In contrast, some cumulenes, such as carbon dioxide and carbon disulfide, are often used as solvents in organic reactions or in the extraction of natural products. The reactivity of some center carbon heterocumulenes in nucleophilic reactions is as follows isocyanates > ketenes > carbodiimides > isothiocyanates. However these reactivities do not relate to the reactivities in cycloaddition reactions. Often reactive cumulenes are isolated as their cyclodimers. Aromatic diisocyanates are more reactive than aliphatic diisocyanates in nucleophilic as well as cycloaddition reactions. 

The cycloaddition reactions are subdivided into di-, tri- and oligomerization reactions, [2-1-1]-, [2-1-2]-, [3-1-2]- and [4- -2] cycloaddition reactions and other cycloaddition reactions. The insertion reactions into single bonds are also discussed. The cyclodimerization or cyclotrimerization reactions are special examples of the [2-1-2] and the [2-I-2-I-2] cycloaddition reactions, respectively. The cumulenes vary in their tendency to undergo these reactions. The highly reactive species, such as sulfines, sulfenes, thioketenes, carbon suboxide and some ketenes, are not stable in their monomeric form. Other cumulenes have an intermediate reactivity, i.e. they can be obtained in the monomeric state at room temperature and only heat or added catalysts cause di- or trimerization reactions. In this group, with decreasing order of reactivity, are allenes, phosphorus cumulenes, isocyanates, carbodiimides and isothiocyanates. 

The click chemistry, involving sulfines, is encountered in their [3-1-2] and [4-1-2] cycloaddition reactions which afford five- and six-membered ring heterocycles, often in high yields. Examples of the [2-1-1] and the [2-1-2] cycloaddition reactions of sulfines are hardly known. 

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... 

Thioketene 5-oxides, which are sulfines with an extended cumulenic system, also participate in the cycloaddition reaction with 2-diazopropane. In this case, exclusive reaction across the C=C bond is observed to form the cycloadduct 29 in 70 % yield. ... 

In contrast to the [4-I-2] cycloaddition reactions of sulfur dioxide with 1,3-dienes, the sulfine derived cycloadducts are stable compounds. 

Sulfines derived from proline 36 also reacted with 2,3-dimethyl-l,3-butadiene to give the expected cycloadducts 37 . During the cycloaddition reactions, asymmetric induction of up to 40 % is observed. The best results are obtained when one of the sultine substituents is a chloro group and when the reaction is performed at -78 °C. All thiopyran j -oxides obtained in this manner are mixtures of diastereomers. 

The cycloaddition reactions of the reactive a-oxo sulfines 45 with dienes are well investigated and [4+2] cycloadducts 46 are obtained. Benzoyl substituted thioaldehyde -oxides already react with 2,3-dimethyl-l,3-butadiene at —78 °C. 

The O -0X0 sulfines can also participate as dienes in cycloaddition reactions with electron-rich olefins, such as vinyl ethers. For example, the stable a-oxo sulfines 49 react with ethyl vinyl ether to give the cycloadducts 50 . 

Complete asymmetric induction is observed in the cycloaddition reaction of 2,3-dimethyl-1,3-butadiene with chiral camphor or sulfoximino substituted sulfines . Excellent yields are obtained for the cycloaddition reaction of sulfoximino sulfines which have the inducing chiral center in close proximity to the sulfine group. 

Cycloadditions Interestingly, sulfur dioxide participated as a dienophile in the [4+2] cycloaddition reaction with 1,3-dienes. In this manner, sulfur dioxide reacts similarly to the related selenium dioxide and the other sulfur dienophiles RN=S=0, RN=S=NR and R2C=S=0 (sulfines). However, the [4+2] cycloadducts derived from 1,3-dienes and sulfur dioxide are only obtained at low temperatures (—80 °C) in a kinetically controlled reaction and the cycloaddition reactions often require the presence of a Lewis acid (CF3COOH or BF3). Above —50 °C the Diels-Alder adducts undergo a cycloreversion and a cheletropic addition of the generated sulfur dioxide to the diene occurs with formation of the corresponding 2,5-dihydrothiophene-1,1-dioxides (sulfolenes). According to ab-initio computations, electrostatic solvent effects are predicted to be of importance in the control of the selec-tivities in this reaction . From linear dienes, the [4+1] cycloadducts are usually obtained. For example, from 1,3-butadiene and SO2 at -20 °C, the cyclic sulfone 25 is obtained in 95% yield. ... 

The cumulenes discussed in this book are subdivided into carbon- and noncarbon cumulenes, and the 1-carbon cumulenes (sulfines, sulfenes, thiocarbonyl S -imides and thiocar-bonyl S -sulfides) are excellent dipolar species. The 2-carbon or the center-carbon cumulenes (carbon dioxide and carbon sulfides) are less reactive but their imides (isocyanates, isothiocyantes and carbodiimides) readily participate in many of the discussed reactions. The 1,2-dicarbon cumulenes (ketenes, thioketenes and ketenimenes) similarly participate in cycloaddition reactions, as well as the more exotic 1,2-dicarbon cumulenes (1-silaalene, 1-phosphaallene and other metal allenes). In contrast, 1,3-dicarbon cumulenes are only... 

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. 

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. 

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