Benzenes 4 + 3 cycloaddition reactions

Pyridazine carboxylates and dicarboxylates undergo cycloaddition reactions with unsaturated compounds with inverse electron demand to afford substituted pyridines and benzenes respectively (Scheme 45). 

Since the first demonstration of a cycloaddition reaction of a, /f-unsaturated sulfones in 1938 by Alder and coworkers85, a variety of a, /3-unsaturated sulfones have been prepared and used as dienophiles. For example, when a mixture of p-tolyl vinyl sulfone and 2,3-dimethylbutadiene in benzene is heated at 145-150 °C for 10 h in a sealed tube, crystals of the cycloadduct (134) are obtained (equation 102). Other examples of this intermolecular cycloaddition reaction are given in Table 12. 

Cossu S., Fabris F., De Lucchi O. Synthetic Equivalents of Cyclohexatriene in [4 + 2 Cycloaddition Reactions. Methods for Preparing Cycloaddncts to Benzene. Synlett W1 1327-1334... 

Cycloaddition reactions catalysed by transition metal complexes are an important tool in the construction of a wide range of carbo- and hetero-cyclic systems, such as benzene, pyridines, triazoles, etc. [7]. In general, these reactions are extremely atom-efficient and involve the formation of several C-C bonds in a single step. Among the innumerable possible catalytic systems for the cycloaddition reaction the NHC-metal complexes have received special attention [7c]. 

In 1989 Jutzi et al. reported the reaction of decamethylsilicocene 50 with tri-n-butylphosphine selenide in benzene at room temperature, leading to almost quantitative formation of a 1,3,2,4-diselenadisiletane derivative 52, a head-to-tail [2+2] cycloaddition reaction product of the initially formed silaneselone 51.35 The intermediacy of silaneselone 51 was experimentally supported by the reaction in the presence of 2,3-dimethyl-1,3-butadiene resulting in the formation of the corresponding [2+4] cycloaddition reaction product 53 (Scheme 14). 

Diarylmethylenecyclopropa[6]naphthalenes 14, unlike their benzene parent counterparts which give cycloaddition reactions at the cyclopropene bridge bond [10a], react on the exo double bond in Diels-Alder cycloadditions (see Sect. 2.1.1) [10b]. The reactions of 14 with the highly electron-deficient acetylenic(phenyl)iodonium triflate 584 give products 586a and 587, which are believed to derive from unstable primary [2 + 2] cycloadducts 585 (Scheme 82) [10b],... 

Mejla-Oneto and Padwa have explored intramolecular [3+2] cycloaddition reactions of push-pull dipoles across heteroaromatic jr-systems induced by microwave irradiation [465]. The push-pull dipoles were generated from the rhodium(II)-cata-lyzed reaction of a diazo imide precursor containing a tethered heteroaromatic ring. In the example shown in Scheme 6.276, microwave heating of a solution of the diazo imide precursor in dry benzene in the presence of a catalytic amount of rhodium I) pivalate and 4 A molecular sieves for 2 h at 70 °C produced a transient cyclic carbonyl ylide dipole, which spontaneously underwent cydoaddition across the tethered benzofuran Jt-system to form a pentacyclic structure related to alkaloids of the vindoline type. 

Even more than [6 + 4] and [8 + 2] cycloaddition reactions, the [2 + 2 + 2] cycloaddition reactions require a very well preorganized orientation of the three multiple bonds with respect to each other. In most cases, this kind of cycloaddition reaction is catalyzed by transition metal complexes which preorientate and activate the reacting multiple bonds111,324. The rarity of thermal [2 + 2 + 2] cycloadditions, which are symmetry allowed and usually strongly exothermic, is due to unfavorable entropic factors. High temperatures are required to induce a reaction, as was demonstrated by Berthelot, who described the synthesis of benzene from acetylene in 1866325, and Ullman, who described the reaction between nor-bomadiene and maleic anhydride in 1958326. As a consequence of the limiting scope of this chapter, this section only describes those reactions in which two of the participating multiple bonds are within the same molecule. 

TVA -Disulfonylsulfodiimides 244 react exothermically with butadiene to give 1-sulfo-nylimino-2-sulfonyl-3,6-dihydro-l,2-thiazines 245 (equation 130)121,122. IV-Aryl-AT-sul-fonylsulfodiimides 246 are much less reactive as dienophiles. The addition to butadiene to yield 247 takes place in boiling benzene (equation 131)123. No cycloaddition reactions of dialkyl- or diarylsulfodiimides are known. 

Process Improvements. Phase 1 Benzene was replaced with a safer solvent, toluene, which was also used for the [2 + 2] cycloaddition reaction, thus facilitating the telescoping of the two reactions. However, dichloromethane was added during the work-up to prevent product precipitation. The product was ciystallized from 2-propanol in 80% yield. The phase I of development eliminated the use of benzene and allowed for telescoping of the two chemical steps. However, a solvent exchange from toluene-dichloromethane to 2-propanol was still needed to crystallize the product. The color of the product after this modification was dark-brown. 

Although pyrroles do not generally participate in Diels-Alder reactions with olefinic dienophiles, the very reactive hexafluoro-Dewar benzene with pyrrole gives the 1 1 and 1 2 adducts, 27 and 28, both of which probably have all-ea o stereochemistry. Some other 7-azabicyclo-heptene derivatives have been obtained via cycloaddition reactions of 7-azaquadricyclanes (see Section II, F). 

Thiophene is present in the benzene fraction from the distillation of coal tar. As with pyrrole and furan, the same type of resonance forms contribute to its overall molecular constitution, and the compound is aromatic in character. There is a difference between thiophene and furan, however, because sulfur is less electronegative than oxygen. Thus, the chemistry of thiophene tends to be closer to that of pyrrole than to that of furan. For example, thiophene does not enter easily into [4 + 2] cycloaddition reactions and quite severe conditions, high pressure (15 bar) and a temperature of 100 C, are necessary in order to force a cycloaddition between it and maleic anhydride. 

While both hydrogenation and epoxidation reactions of (7) (and substituted forms) occur on the oxepin valence tautomer, cycloaddition reactions proceed more readily on the arene oxide form (where the diene is closer to planarity). Thus the dienophiles DM AD and maleic anhydride (MA) readily yielded [4 + 2] cycloadducts with (7) as shown in Scheme 22 (67AG(E)385). A similar type of singlet oxygen cycloaddition reaction gave an unstable endoperoxide (106) which upon heating yielded trans-benzene trioxide quantitatively (equation 14). (75JOC3743). 

Substituted l,2,4-triazoline-3,5-diones are excellent dienophiles which react rapidly at room temperature with oxepins, but particularly with the arene oxide valence tautomer. A similar [4+2] cycloaddition reaction between the episulfide tautomer of thiepin (44) and 4-phenyl-l,2,4-triazoline-3,5-dione has been reported (74AG(E)736>. Benzene episulfide (the valence tautomer of thiepin 44) was generated in situ by thermal decomposition of the diepisulfide (151) at 20 °C and trapped as a cycloadduct at the same temperature (equation 34). A 1,3-dipolar cycloaddition reaction between thiepin (152) and diazomethane has been reported (56CB2608). Two possible cycloadduct products are shown since the final structure has not been unequivocally established (equation 35). 

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