3-Sulfolene in Diels-Alder reactions

W-Methylpiperidine, 52, 127 3-Methyl-3-sulfolene, in Diels-Alder reaction, 50, 48 MODIFIED CLEMMENSEN REDUCTION CHOLESTANE, 53, 86... 

Pyrrole-fused 3-sulfolenes 221 undergo thermal extrusion of sulfur dioxide to produce highly reactive o-quinodi-methanes which can be trapped in Diels-Alder reactions (Scheme 23) <1997H(46)199, 1997TL3639>. The resulting cycloadducts 222-227 are important starting compounds in porphyrin synthesis. 

The Diels-Alder reaction is usually reversible and has been used to protect double bonds. A convenient substitute for butadiene in the Diels-Alder reaction is the compound 3-sulfolene since the latter is a solid that is easy to handle while the former is gas. " Butadiene is generated in situ by a reverse Diels-Alder reaction (see 17-20). 

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. 

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. 

There are other kinds of cycloadditions, too. The [4 + 1] cycloaddition, a cheletropic reaction, usually goes in the retro direction for entropic reasons. 3-Sulfolene (butadiene sulfone, 2,5-dihydrothiophene 1,1-dioxide) undergoes a [4 + 1] retro-cycloaddition to generate S02 and 1,3-butadiene, which can undergo a Diels-Alder reaction with a dienophile. It is much more convenient to... 

For multistep syntheses that include a Diels-Alder reaction, corresponding 1,3-dienes are necessary. They can be prepared by the method described. In many cases, the 1,3-diene is not isolated, but the Diels-Alder reaction is carried out with 3-sulfolene and dienophile in boiling xylene. 

Yet another ingenious method of stereospecifically synthesizing c/is-2,5-dialkylated 3-sulfolenes is to start with the sulfolane (358). Sequential alkylation (Bu"Li/RX) leads stereospecifically to cis-(359). A retro Diels-Alder reaction followed by cheletropic extrusion of SO2, results in (360) (Scheme 74) <83TL1247>. 

The preparation of 2,3-dimethylene heteroaromatics (DMHAs), as analogues of orthoquinodimethanes, has attracted a good deal of attention in recent years. Such systems are often quite labile, and one of the most commonly employed synthetic strategies to them has been to build the required heteroaromatic ring fused to a sulfolene, as a direct precursor to the DMHA [79]. Some interesting work has been done on Diels-Alder reactions from DMHAs derived from fused sulfolenes, and these are covered in more detail in Section 6.5. 

In our laboratories, problems have been encountered in predicting the stereoselectivity of intramolecular Diels-Alder reactions from 2,3-disubstituted sulfolenes bearing a methyl ester or dimethylamide in the 3-position, intermediate dienes of differing geometries perhaps being responsible [70,72,75]. Model sulfolenes we therefore constructed to find out the effect of changing substituents... 

Over recent years a diverse range of methods has been developed for preparing selectively functionalized 3-sulfolenes. The use of such compounds as diene precursors for intermolecular and intramolecular Diels-Alder reactions has also been explored extensively. Thus, it is now possible to prepare and utilize substituted sulfolene intermediates in efficient strategies for the synthesis of complex organic molecules. There is, however, scope for more research into the basic principles underlying the preparation and reactions of substituted sulfolenes. 

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