Thiophene-1,1-dioxides, cycloaddition

Fig. 30. [6 +4] Cycloadditions of fulvenes to electron-rich species, and of aminofulvenes to electron-deficient thiophene dioxides...

Diels-Alder cycloadditions of thiophene-1,1-dioxides with cyclopentadiene can take place either in the (2-1-4) or (4-1-2) mode depending on whether the thiophene dioxide has two or one electron-withdrawing substituents <2006T4139>. 1,3-Dipolar cycloaddition of benzo[/)]thiophene 1,1-dioxide with azomethine ylides has been reported <2006TL5139>. 

Cycloaddition of thiophene dioxides with alkenic dienophiles often directly leads to the formation of a benzene ring. This can be attained by extrusion of sulfur dioxide from the initial adducts, followed by 1) elimination of a small molecule, 2) an intramolecular hydrogen transfer, and 3) (accidental) oxidative dehydrogenation under applied conditions. 

The primary adducts, cyclohexadiene derivatives, formed by [4+2] cycloaddition of thiophene dioxides with dienophiles, may further undergo [4+2] cycloaddition with the dienophiles. Thus, the adducts 84 of 3,4-di-ferf-butylthiophene dioxide 83 with maleic anhydride and AT-phenylmaleimide further react with these dienophiles to give excellent yields of bis-adducts, which are composed of the endo-endo and endo-exo isomers, 85a and 85b (Scheme 49) [160]. A similar reaction was also observed with 3,4-dichlorothiophene 1,1-dioxide with N-butyl- and A-p-nitrophenylmaleimides (Scheme 50) [133]. The reaction of highly congested thiophene dioxides 87 with 4-phenyl-1,2,4-triazoline-3,5-dione provides a unique pyridazine synthesis since the bis-adducts 88 are converted into the corresponding pyridazines 89 in one pot and in good yields by treatment with KOH in methanol (Scheme 51) [174]. 

The synthetically most important reaction that belongs to this category would be [4+2] cycloadditions of highly congested thiophene dioxides with alkynic dienophiles (Scheme 55) [39,40,159]. These reactions afford o-di-ferf-butyl-, o-dineopentyl-, and o-di(l-adamantyl)benzene derivatives in good yields, synthesis of which is very difficult by other means. 

Only one example of an ene reaction is reported [40]. As already described, ben-zyne and thiophene dioxides undergo [4+2] cycloaddition. However, the reaction of 3,4-dineopentylthiophene 1,1-dioxide with benzyne affords compound 98, the product of an ene reaction. The other two products, 99 and 100, result from [4+2] cycloaddition (Scheme 59). 

As described in Sect. 3.1.2, some thiophene dioxides dimerize in a [2+4] cycloaddition manner and the resulting adducts undergo ring opening to give alkynes [105,107]. A supplementary example is given below (Scheme 82). 

Most of the synthetic approaches towards benzoannelated [2.2]paracyclo-phanes use the Diels-Alder reaction to build up the annelated rings [18,22,29]. [2.2]Paracyclophane-l-ene (32) and [2.2]paracyclophane-1,9-diene (42) can be considered as the simplest dienophiles for this purpose. Since the first syntheses of these compounds in 1958 by Cram et al. [32], various attempts have been made to get them to react with dienes in terms of Diels-Alder reactions. However, [2 + 4] cycloadditions were never observed [33], and could not be facilitated either by the application of high pressure, or the presence of Lewis acid catalysts Diels-Alder adducts were not even obtained with dienes such as tetrachloro-thiophene dioxide, known for its high reactivity in [2 + 4] cycloadditions with an inverse electron demand. All the more surprising was the observation that monoene 32 reacts smoothly with dimethyl l,2,4,5-tetrazine-3,6-dicarboxylate at room temperature leading to a dihydropyridazine-annelated paracyclophane 39 in high yield [34a]. As reported for other tetrazine Diels-Alder reactions... 

With hapten 134, a close analog of the transition state, Hilvert etal developed the Diels-Alderase antibody 1E9 in which elimination of the product is programmed to avoid product inhibition. In their study, the cycloaddition of reactive thiophene dioxide 130 and maleimide 131 affords the unstable adduct 132 that spontaneously eliminates SO2 followed by air oxidation to yield a stable phthalimide 133 (Scheme 23). The structure of the final product 13 3 is significantly different from that of the Diels-Alder adduct 132, and product... 

N-Phenyltriazolinedione [PTD] continues to be a popular probe for the study of reactions of alkenes and dienes. Synthetically, PTC can serve as either a N=N wnthon or a 1,3-diene protecting group. The reaction of thiophene dioxide (150) with PTD (2 eq.) generated bis adduct (ISl) with the loss of SO2. Intermediate (151) decomposed with KOH-MeOH to yield the pyrazine (152) in 84% [94TL(35)2709]. Urazole (153), several steps removed from a PTD cycloaddition, when treated with KOH-EtOH yielded the novel oxazolidinone (154) [94JCS(P1)2335]. The PTD cycloadduct was used as a... 

The cycloaddition reactions of thiophene oxides and dioxides (290 and 291280,281) have already been discussed (Section V.A). 

An interesting cycloheptatriene (182) synthesis has been described using thiophene 1, 1-dioxides (180) and cyclopropenes 181 (equation 121)ns. Concerted [4 + 2]cycloaddition and subsequent cheletropic extrusion of sulfur dioxide are suggested by the second-order kinetics (first in each reactant), and by the large negative activation entropy. 

The synthetic utility of o-quinodimethane generated by cheletropic elimination of S02 has been amply demonstrated by Oppolzer and Nicolaou, who have conducted an intramolecular cycloaddition coupled with the alkylation of 1,3-dihydrobenzo[c]thiophene 2,2-dioxide122. When 1,3-dihydro-l-(4-pentenyl)benzo[c]thiophene 2,2-dioxide (201) prepared from 1,3-dihydrobenzo[c]thiophene 2,2-dioxide and 4-pentenyl bromide is heated in di-n-butyl... 

Nakayama J, Sugihara Y (1999) Chemistry of Thiophene 1,1-Dioxides. 205 131-195 Namboothiri INN, Hassner A (2001) Stereoselective Intramolecular 1,3-Dipolar Cycloadditions. 216 1-49... 

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