Cycloaddition reactions heat formation

Another synthetically intriguing method of ring formation is based upon the intramolecular cycloaddition reaction formulated in Scheme 28 (82CC613). The initially formed adduct will undergo cleavage to the carbazole on heating. 

The intramolecular cycloaddition has proven to be the method of choice for the preparation of steroids. A diastereomeric mixture of 204, prepared from 191 and tosylate 203 has been cleanly converted to dl-estra-1,3,5(10)-trien-17-one (205) in 85% yield (equation 130). A second example of the intramolecular cycloaddition reaction is the formation of the cycloadduct (209), the key intermediate in a synthesis of the As-pidosperma alkaloid aspidospermine, upon heating 208 at 600 °C (equation 131)124. The sulfone 208 can be prepared by reaction of 3-ethyl-3,4,5,6-tetrahydropyridine (206) with the acid chloride 207. 

Thermal reactions and 1,3-dipolar cycloaddition reactions Thermally mesoionic oxatriazoles are relatively stable. Heating of (85) in tolane (97) at 200 °C for 20 d in the presence of LiCl induces C02 fragmentation and formation of cycloadduct (99) in 37% yield. There is no bimolecular reaction as found in the case of the sydnones and isosydnones (equation 56) (68CB536). 

In an analogous reaction of (2) with norbomadiene, the tetracyclic adduct (116) is formed which on heating undergoes a retro Diels-Alder reaction with formation of the thiophene derivative (117). Further cycloaddition reactions of mesoionic 1,3-dithiolones have been carried out with cyclopentadiene, 1,3-cyclohexadiene and 1,5-cyclooctadiene (78CB3037). 

The Kuehne synthesis has also been adapted to the preparation of 18-methylenevincadifformine (230).108" Unexpectedly, when (230) was hydrolysed by alkali, and the acid thus obtained was heated briefly in 3% aqueous hydrochloric acid, the only product that could be isolated was a diene-imine which has been assigned the structure (231). This is the first report of an intramolecular [4tt + 2n cycloaddition reaction involving an indolenine. When heated in benzene in the presence of toluene-p-sulphonic acid, 18-methylenevincadifformine (230) is smoothly hydrolysed and decar boxy lated, with exclusive formation of the indolenine (232) this can be quantitatively transformed into (231) by heating with 3% aqueous hydrochloric acid (Scheme 33). 

An important property of metal-bound phosphole ligands is their ability to undergo additional reactions not possible in the noncomplexed form. This is nicely illustrated by the thermally induced reactions of the palladium(ll) complex of 1-phenyl-3,4-dimethylphosphole 341 <1996IC1486>. Heating complex 341 at 145 °C in solution or at 140 °C in the solid state led to the formation of a mixed 7-phosphanorbornene-phosphole complex 343 (Scheme 114). These intramolecular [4-1-2] cycloaddition reactions are believed to proceed via the initial formation of a diallyl 1,4-biradical TS 342. Further examples of this type of reaction may be found in Section 3.15.12.1.1. 

A cycloaddition reaction involves the concerted formation of two ct-bonds between the termini of two tt-systems. The reverse reaction involves the concerted cleavage of two ct-bonds to produce two TT-systems. The simplest example being the hypothetical combination of two ethene molecules to give cyclobutane. This does not occur under normal heating, but the cycloaddition of 1,3-butadiene to ethene does, and this is an example of the Diels-Alder reaction. 

Some of the transformations listed above do not involve free carbenes. For example, heating an a-diazocarbonyl compound in the presence of an alkene may trigger a [3 + 2] cycloaddition reaction rather than formation of the acylcarbene. The resulting 4,5-dihydro-3//-pyrazole may undergo spontaneous ring contraction with concomitant loss of nitrogen. (For the transformation of 4,5-dihydro-3/f-pyrazoles to cyclopropanes, see Section 4.2.1.1.)... 

Cycloadditions are an important tool for the construction of cyclic systems of different ring-size. The reactions usually proceed smoothly and at most require moderate application of heat. Formation of 6-membered rings are realized via [4 + 2] cycloaddition [(het-ero) Diels-Alder], 5-membered rings via the [3 + 2] cycloaddition [1,3-dipolar] and 4-membered rings via the [2 + 2] cycloaddition. 

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