Sulfenes 4+2 cycloaddition reactions

Practically speaking, almost all syntheses of these systems are based on the enamine-sulfene cycloaddition reaction " . The thietane sulfone thus obtained yields, by elimination of R2NH, the desired unsaturated, four-membered sulfone... 

Vinyl ethers undergo many cycloaddition reactions similar to those which take place with enamines. In general, however, these cycloaddition reactions with vinyl ethers take place less readily than those with enamines. These reactions include cycloaddition of vinyl ethers with ketene (200-205), phenyl isocyanate (206), sulfene (207,208), methyl acrylate (209), diethyl acetylenedicarboxylate (210), and diphenylnitrilimine (183). 

Although the yields of the above reactions are high and the procedure is simple186, there are some apparent disadvantages the selection of the sulfene substituents R1 and R2 is limited, depending on the availability of the sulfonyl chloride precursors the cycloaddition leads to a mixture of cis- and trans-substituted thietane dioxides the cycloaddition reaction is reversible202 and several further transformations are necessary if a dioxide without 3-lV-substituent is required. 

Alkylidene sulfenes (75), generally prepared by the dehydrohalogenation of alkylsulfonyl chlorides, add readily to electron-rich multiple bonds. For example, with enamines, the thietane dioxide (e.g., 76) is formed diazoalkanes yield thiirane dioxides (episulfones) and imines (Schiff bases) afford 1,2-thiazetidine 1,1-dioxides. There are available numerous reviews of sulfenes, including cycloaddition reactions.102... 

Sulfonyl imides (78) are, like sulfenes, prepared by dehydrohalogenation of the corresponding sulfonyl chlorides (79) (usually called sulfamoyl chlorides). Like sulfenes, they take part in [2 + 2] and [4 + 2] cycloaddition reactions with electron-rich alkenes or with 1,3-dienes, yielding 1,2-thia-zetidine 1,1-dioxides (80)104 or dihydro-1,2-thiazines (81),105 respectively. 

The most direct approach to the four-membered S-ring is cycloaddition of sulfenes to alkenes. The sulfenes are generated in situ by base-induced de-hydrohalogenation of sulfonyl chlorides. Because of their special susceptibility to cycloaddition reactions, research into the chemistry of sulfenes is expanding. 

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. 

Thermal and photochemical cycloaddition reactions of 27r-electron species represent an important synthetic approach to four-membered rings. The reactions summarized in this section include 2 + 2 cycloaddition reactions of thioketones, thioketenes, isothiocyanates, sulfenes and iminosulfenes with alkenes, allenes, ketenes, ketenimines and alkynes. 

Sulfenes are reactive 27r-components in cycloaddition reactions and treatment of methanesulfonyl chloride with triethylamine in the presence of (CF3)2C=NCOPh gives the 1,2,5-oxathiazine (119) via a formal [4+2] cycloaddition of sulfene to the heterodiene (69IZV2059). 

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

An AMI semiempirical method was used to investigate the Diels-Alder cycloaddition reactions of vinyl sulfenes with buta-1,3-dienes.156 The reactivity and stereoselectivity of vinyl boranes have been reviewed.157 Aromatic methyleneamines undergo reverse-electron-demand Diels-Alder reactions with cyclopentadiene, norbom-ene, and vinyl sulfides.158... 

Sultams are accessible using a [2+2] cycloaddition reaction between an alkylsulfonyl chloride and an aryl or /-butylimine, better yields being obtained in the latter case. A diastereoselective synthesis of these /3-sultams has been described where 1,3-asymmetric induction occurs in a [2+2] cycloaddition between a sulfene intermediate and... 

Azine approach. Examples of this heterocyclic ring system have been prepared from 3,4-dihydroisoquinoline azomethine imines (706) and sulfenes by 1,3-dipolar cycloaddition reactions. The products are l,5,6,10b-tetrahydro-3H-[l,2,3]thiadiazolo[4,3-a]isoquinoline 2,2-dioxide derivatives (707) (75JOC2260). 

Cycloaddition Reactions Across Other Bonds. The reaction of benzoyl-sulfene 265, generated in situ, with DCC gives a mixture of the [2 + 2] cycloadducts 266 and the [2 + 4] cycloadducts 261 ... 

Scheme 13 [2,3]Sigmatropic rearrangements of nitroaryl propargyl sulfenates to allene sulfoxides and their cycloaddition reactions...

Sulfenes are important in synthetic organic chemistry because they participate in a range of useful cycloaddition reactions, leading to the formation of fourmembered and other cyclic compounds. Sulfenes will form cycloadducts with the following types of substrates. 

Sulfenes often undergo a [2 + 2] cycloaddition reaction with halocarbonyl compounds thus, chloral (130) adds to sulfene (75) to give the p-sultone (131) (Scheme 79). 

Transition metal complexes in synthesis of heterocycles 80KGS147. Tropone derivatives, cycloaddition reactions with sulfenes or ketenes... 

Acyl sulfenes, like all sulfenes, prefer to participate as 2it components of [2 + 2] or [4 + 2] cycloadditions (Chapter 5). Nonetheless, a range of [4 + 2] cycloaddition reactions of acyl sulfenes have been described46,47 (Scheme 8-XII), including their 4n- participation in dimerization reactions46-48 and reactions with imines,49 carbodiimides,50 ketenimines,51 1-azirines,52 vinyl ethers,53 and ketenes.47 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. 

AAAcylimines, e.g., 4, are the most widely recognized and the most extensively investigated hetero-2-azadiene system capable of participation in Diels-Alder reactions, and comprehensive reviews have been published.7,71 In general, substituents X and Y are strongly electron-withdrawing groups and consequently the AAacylimines participate as electron-deficient partners in cycloaddition reactions with electron-rich dienophiles. Diels-Alder reactions of electron-deficient /V-acylimines with vinyl ethers, enamines, olefins, sulfenes, acetylenes, and the carbon-carbon or carbon-oxygen double bond of ketenes have been detailed.57 71 This 47t participation of electron-deficient AAacylimines does complement the ability of many simple AAacylimines to behave as 2ir dienophile components in Diels-Alder reactions with typical electron-rich dienes.6... 

Schenone and coworkers2 00 have published a series of papers showing the generality of the sulfene-ketoenamine cycloaddition reaction (equations 87-90). 

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. 

Carbon cumulenes undergo [2+2] cycloaddition reaction with numerous double or triple bonded substrates to give four-membered ring cycloadducts. Examples of cycloaddition to C=C, C=C, C=0, C=N, C=S, N=0, N=N. N=S. S=0, P=C, P=0, P=N and P=S bonds are known. When the two adjacent double bonds in the cumulenes are different, cycloaddition across either one of the double bonds occurs, and sometimes addition across both bonds is observed. However, more often the cycloaddition reactions follow only one pathway. As a general rule, in ketenes the non-catalyzed cycloaddition occurs preferentially across the C=C bond, whereas catalyzed cycloaddition reactions proceed across the C=0 bond. In thioketenes, isothiocyanates and sulfenes addition mainly occurs across the C=S bond. In isocyanates addition across the C=N bond is preferred. 

The [3+2] cycloaddition reactions of cumulenes as 1,3-dipolarophiles are also well known. Huisgen in 1963 demonstrated the wide scope of the dipolar [3+2] cycloaddition reactions, which often proceed in high yields, and consequently these reactions rival the Diels-Alder reactions as valuable synthetic tools. The oldest example of a [3+2] cycloaddition reaction is the reaction of isocyanates with nitrones, discovered by Beckmann in 1890, but the general character of this reaction was discovered much later. Because of the dual character of heterocumulenes, such as isocyanates, the reaction can occur across either one of the double bonds and sometimes both reaction products are isolated. In general, the [3+2] cycloaddition reaction proceeds across the same double bonds, which also participate in the [2+2] cycloaddition reactions. Ketenes react predominantly across their C=C bonds, isocyanates across their C=N bonds and sulfenes across their CHS bonds. 

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... 

The polarization of the C=S double bond in sulfenes as shown in 1 and 2 account for their reactivity in cycloaddition reactions. 

Cycloaddition reactions, especially [2+2] cycloadditions, are prominent in sulfene chemistry and even insertion of sulfene into metal-hydrogen bonds is observed. ... 

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 cycloaddition reaction of sulfenes to numerous electron-rich alkenes is a general reaction. In this respect sulfenes are very similar to ketenes. An example is the reaction of sulfenes with enamines to give aminothietane sulfones 8. 

Ketene acetals also undergo a facile [2-1-2] cycloaddition reaction with sulfenes. For example, a 79 % yield of 3,3-diethoxythietane 1,1-dioxide 17 is obtained in the reaction of ketene diethylacetal with sulfene. ... 

A [2+2] cycloaddition reaction across a polarized C=0 bond also occurs. Reaction of chloral with sulfene affords a j8-sultone 24 . 

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