Dienes sulfolene dioxides

The most synthetically useful cheletropic elimination involves 2,5-dihydrothiophene-1,1-dioxides (sulfolene dioxides). At moderate temperatures they fragment to give dienes and sulfur dioxide.301 The reaction is stereospecific. For example, the dimethyl derivatives 22 and 23 give the E,E- and Z,E-isomers of 2,4-hexadiene, respectively, at temperatures of 100°-150°C.302 This stereospecificity corresponds to disrotatory elimination. 

A synthetically useful type of a cheletropic reaction involves 2,5-dihy-drothiophene-1-1-dioxides (sulfolene dioxides). These compounds can either be made by independent synthetic routes or made by cycloaddition reactions from dienes and sulfur dioxide. At elevated temperatures the ring fragments to sulfur dioxide and a diene.For example, the two dimethyl derivatives 5 and 6 fragment to sulfur dioxide and rmAT5, ran5-2,4-hexadiene and c/5,fr<2 5-2,4-hexadiene, respectively, at temperatures of 100-150°C. The cleavages are stereospecific and involve disrotatory motion of the substituents at C-2 and C-5 similar to the pyrroline decomposition described previously. This reaction has proven to be a satisfactory... 

Sulfur dioxide acts as a dienophile ia the Diels-Alder reaction with many dienes (253,254) and this reaction is conducted on a commercial scale with butadiene. The initial adduct, sulfolene [77-79-2] is hydrogenated to a solvent, sulfolane [126-33-0] which is useful for selective extraction of aromatic hydrocarbons from... 

The thiophene ring system can be utilized as a synthetic scaffold for the preparation of nonthiophene materials as the sulfur moiety can be removed by reduction (desulfurization) or extrusion (loss of SO2). The extrusion of sulfur dioxide from 3-sulfolenes (2,5-dihydrothiophene 1,1-dioxides) give dienes (butadienes or o-quinodimethanes) that can be utilized to prepare six-membered rings by cycloaddition chemistry. For example, thermolysis of 3-sulfolene 120 provided tricyclic pyrazole 122 via an intramolecular cycloaddition of the o-quinodimethane 121 that results by extrusion of sulfur dioxide <00JOC5760>. Syntheses of 3-sulfolenes 123 and 124 <00S507> have recently been reported. 

Since the first report in 1914 of the formation of a butadiene-sulfur dioxide adduct [538], much work has been carried out on the reaction of conjugated dienes with sulfur dioxide and its applications in synthetic strategies. Two pathways can and have been observed a cheletropic reaction (to 2s + ir 4s) yielding 3-sulfolenes and (4 -ns + tt 2s) hetero-Diels-Alder addition yielding sultines (see [539] and [540] and references... 

The thermal retro-reaction of 3-sulfolenes to dienes and sulfur dioxide occurs under mild conditions (about 120-200°C), and is, as predicted from the Woodward-Hoffmann rules, a disrotatory process so for 2,5-dimethyl-3-sulfolenes [541,542] ... 

Finally, the cycloaddition of sulfur dioxide to dienes leading to either 3-sulfolenes or the corresponding sultines has been studied in detail <02CEJ1336, 02HCA712, 02HCA733, 02HCA1390>... 

A report of Backer and Blaas6 is responsible for evolution of the present procedure these workers were first to conduct a Diels-Alder synthesis utilizing a 3-sulfolene in place of the free diene (by heating the cyclic adduct of sulfur dioxide and 2-methyl-3-thiomethyl-1,3-butadiene with maleic anhydride). The generality of the method as a variant of the conventional diene synthesis is limited largely by the availability of the appropriate 3-sulfolene its greatest utility, perhaps, will be presently realized in those diene reactions normally requiring 1,3-butadiene, since 3-sulfolene itself is now the least expensive and most widely available diene cyclic sulfone. 

I, 3-Dienes Allyidiphenylphosphine. Bromo-raethanesulfonyl bromide. 1,3,3a,4JJd-Hexahydro-4,7-methaiiobenzo[c)lhiophene 2,2-dioxide. Molybderjium carbonyl. Nickel(II) chloride-Zihc. 3-Sulfolene. Te-trakis(triphenylphosphine)palladium. 

Few examples of functionalization on the benzene ring of benzisothiazole have been reported (see Section 4.05.7.2). Studies on the reactivity of unsaturated chains in cycloaddition reactions have been reported (see Section 4.05.7.3). The high reactivity of 4-vinylisothiazolin-3-one A-oxides in Diels-Alder cycloadditions, both as diene and dienophile, is illustrated by their tendency to dimerize. 5-Vinylisothiazole A,A-dioxides react at the vinyl function with different 1,3-dipoles. Isothiazolo-3-sulfolenes 265 give an o-quinodimethane which can be trapped with a dienophile. Different isothiazole derivatives substituted with a carbon chain functionalized with heteroatoms have been prepared as ligands for the formation of complexes. 3-Oxocamphorsulfonimide reacts with the anion of alkynes and several studies on the reactivity of the products with electrophiles are reported. 

Five membered ring sulfones (thiolene-1, 1-dioxides, sulfolenes or dihydrothiophene-1, 1-dioxides) can be obtained by peracid oxidation of tetrahydrothiophene. The extrusion of sulfure dioxide from dihydrothiophene-1,1 dioxides or sulfolenes like (178) has been much studied as it provides a synthetic route to dienes, e.g. butadiene (152) (Scheme 70). The reverse reaction provides a method of synthesis of sulfolene (178) from butadiene (152) and sulfur dioxide. Thiolene dioxides or sulfolenes can be generally prepared by addition of sulfur dioxide to conjugated dienes for example, 1,4-dimethylbutadiene (179) in the presence of sulfure dioxide, triethylamine and formic acid affords 2,5-dimethylsulfolene (180) (Scheme 71). 

Sulfur dioxide extrusion (desulfonation) from sulfolenes provides a useful procedure for generation of the diene in the presence of a dienophile, thus facilitating in situ Diels-Alder cycloadditions as illustrated by Scheme 72. The reaction in Scheme 72 involves the in situ formation of 2-cyanobutadiene (181) which then undergoes [4+2] cycloaddition with the dienophile maleimide to yield the adduct (182). 

The term "cheletropic reaction" defines reactions in which two a bonds to a single atom are made or broken conceitedly. A widely studied example, theoretically as well as experimentally, is the cheletropic elimination of sulfur dioxide from a cyclic sulfolene to generate stereochemically pure dienes or polyenes. ... 

Dihydrothiophenes are oxidized to 1,1-dioxides by m-chloroperoxybenzoic acid. These compounds are also accessible by [4+1] cycloaddition of 1,3-dienes and sulfur dioxide. For instance, butadiene reacts even at room temperature with liquid sulfur dioxide to give an adduct 2,5-dihydrothiophene 1,1-dioxide, commonly known by the trivial name 3-sulfolene ... 

Sulfolenes are masked 1,3-dienes [33]. At about 150°C they undergo [4+1] cycloreversion (cycloelimination) into 1,3-dienes and sulfur dioxide. As this is a thermal concerted reaction, it proceeds in a... 

Chloro-4-fluorothiophene-1,1-dioxide 234, a new synthetically useful fluoro-diene was prepared from commercially available 3-sulfolene. This compound reacts with different types of dienophiles acetylenes, alkenes, furans quinine, and antracene giving the 3-fluoro-4-chloro-substituted arenes or cyclic chlorofluorodienes. " ... 

Cycloadditions of diene intermediates derived from 3-sulfolenes have been utilized to synthesize a variety of compounds. Diels-Alder reaction of furan 202 with excess DMAD initially gave intermediate 3-sulfolene 203. Extrusion of sulfur dioxide gave diene 204 which further reacted with DMAD to give ester 205 . Similarly, 2-bromopyrrole 206 reacted with excess DMAD to give ester 207 . Finally, an intramolecular cycloaddition of the diene derived from 3-sulfolene 208 gave ketone 209 . 

Cheletropic Cycloadditions. If an atom can both donate an electron pair and accept an electron pair to move to a higher covalency, it can act as a dienophile to a diene. Such is the case with the sulfur atom in sulfur dioxide and with phosphoms in tricovalent halides. This type of cycloaddition is called cheletropic, and results in the formation of 5-membered rings. The reaction of butadiene with SO2 is particularly important it is conducted on a commercial scale to produce the cyclic sulfone 5.18 (called sulfolene). Its hydrogenation product 5.19 (sulfolane) is widely used as a nonaqueous highly polar solvent. Substituted dienes also participate in the cycloaddition. Here, the sulfur can donate its electron pair while accepting an electron pair to form a new carbon-sulfur bond. 

A variety of methods are available for preparing 2-substituted sulfolenes, as described in Section 6.3. The extrusion of sulfur dioxide is a concerted stereospecific process, and has been shown to follow a disrotatory pathway. Sulfur dioxide extrusion from mono-2-substituted sulfolenes could in principle lead to ( )- or (Z)-diene formation through alternative disrotatory modes of reaction. 

Sulfur dioxide extrusion from a-hydroxy sulfolenes (194a-f) also appears to give ( )-dienes [55,118] (Scheme 6.63, Table 6.26). Rearrangement of dienes such as (195f) was found to occur, but this could be avoided by protecting the alcohol as a silyl ether [92]. 

In early studies involving sulfolene-based synthetic approaches to alkaloids, intramolecular Diels-Alder cyclizations were carried out between dienes derived from monosubstituted sulfolenes and enamide dienophiles [80,81]. For example, acid chloride (233) reacted with imine (234) to provide enamide (235). Upon heating, this extruded sulfur dioxide and the intermediate diene cyclized to provide tricycle (236) stereoselectively. A straightforward sequence of steps was used to convert the Diels-Alder product into ketone (237), which had been used previously as a precursor to aspidospermine (238) (Scheme 6.73). 

Sol 1. (b) Selenites on oxidation with hydrogen peroxide (or ozone or m-CPBA) give selenoxides. The latter in the presence of a p-hydrogen undergoes an intramolecular syn elimination to leave behind an alkene and selenenic acid. The diene component is generated in situ by thermal sulfur dioxide extmsion from sulfolene in a reverse reaction and is then trapped by the dienophile in a Diels—Alder reaction. 

Sol 2. (i) Butadiene sulfone or 3-sulfolene, a solid, is a convenient substitute for gaseous buta-1,3-diene. Diels—Alder reaction between buta-1,3-diene and dienophiles with low reactivity usually requires prolonged heating above 100 °C. This makes a procedure rather dangerous, if neat buta-1,3-diene is used, and requires special equipment for work under elevated pressure. Alternatively, buta-1,3-diene can be generated in situ by thermal sulfur dioxide extrusion from sulfolene, in which case no buildup of buta-1,3-diene pressure could be expected as the liberated diene is consumed in the cycloaddition, and, therefore, the equilibrium of the reversible extrusion reaction acts as an internal safety valve. ... 

The diene used in this experiment, 1,3-butadiene, is a gas at room temperature (bp -5 °C), which makes it a difficult reagent to measure and handle in the laboratory. Fortunately, 1,3-butadiene can be generated in situ from 3-sulfolene, a solid reagent that is easily handled. In an example of a refro-cycloaddition reaction, 3-sulfolene decomposes at a moderate temperature to yield sulfur dioxide and 1,3-butadiene. 

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