Cyclobutadienes, Diels-Alder reaction

Retro Diels-Alder reaction of nitrogen bridgehead compound 415 at 100 °C afforded 6,7,8,9-tetrahydro-4//-pyrido[l,2-u]pyrimidin-4-one and cyclobutadiene (97SC195). 

Cyclo butadiene is highly reactive and shows none of the properties associated with aromaticity. In fact, it was not even prepared until 1965, when Rowland Pettit of the University of Texas was able to make it at low temperature. Even at —78 °C, however, cyclobutadiene is so reactive that it dimerizes by a Diels-Alder reaction. One molecule behaves as a diene and the other as a dienophile. 

With application of reasonable values for trapping parameters and AS2, it was possible to bracket the enthalpy and entropy of activation for isomerization of cyclobutadiene. Hence, A/Zj was estimated to fall between 1.6 and lOkcal/mol, where the upper limit was consistent with theoretical predictions for square-planar cyclobutadiene. Most surprising, though, was the conclusion that AS for automeriza-tion must lie between -17 and -32cal/(molK), based on the AS values normally observed for Diels-Alder reactions as a model for AS2. ... 

Besides the above configurational and steric factors electronic effects of substituents have also been studied on Diels-Alder reaction. How the electronic and steric factors both operate is best afforded by cyclobutadiene which is a highly reactive species and undergoes Diels-Alder reaction even at very low temperature to give a mixture of the following two products. 

Gibson and co-workers have introduced a well-designed latent cyclobutadiene moiety. Compound 49 reacts with a phenylethyne-cobalt complex to give PKR product 50 as a single diastereomer that resulted from the reaction at the less sterically hindered site, and 50 was subjected to the retro-Diels-Alder reaction at 205 °G under a vacuum of 6 torr to give 51 (Equation (23)). ... 

Cyclobutadienes represent very reactive alkenes that undergo both [2 + 2] as well as [4 + 2] cycloadditions. Both the cyclodimerizations, mixed [2 + 2] cycloadditions and Diels-Alder reactions of these reactive species have been reviewed (see Houben-Weyl, Vols. 4/4, p 231 and E 17 f, Section 10B). In most instances the initially formed cyclodimer is tricyclo[4.2.0.02-5]octa-3,7-diene (36) and has the all cis-syn configuration. This is attributed to the concerted [4n -I- 2n] cycloaddition mechanism in which stereochemical control is affected by secondary orbital interactions. 

Show the products expected from the Diels-Alder reactions. Use orbital interaction theory to develop a bonding scheme for rectangular cyclobutadiene and explain why rectangular cyclobutadiene may be exceptionally reactive as a diene in Diels-Alder reactions. 

The dimerization of cyclobutadiene is a Diels-Alder reaction in which one molecule of cyclobutadiene acts as a diene and the other as a dienophile. 

Cyclobutadiene (26) is antiaromatic and its isolation is not possible. Flowever, it can be stabilized by -coordination of Fp+ to one of the double bonds to give 27, and the uncomplexed double bond in 27 undergoes Diels-Alder reaction with cyclopentadiene to give 28 [4]. As described in Section 9.2, cyclobutadiene (26) can be stabilized as a diene by the )/4-coordination of Fe(CO)3. 

Cyclobutadiene has never been isolated and purified. It undergoes an extremely fast Diels-Alder dimerization. To avoid the Diels-Alder reaction, cyclobutadiene has been prepared at low concentrations in the gas phase and as individual molecules trapped in frozen argon at low temperatures. This is not the behavior we expect from a molecule with exceptional stability ... 

Scheme 72 A cyclobutadiene surrogate for the PKR. Tandem [2 + 2 + 1]/retro Diels-Alder reaction...

Supporting evidence for the above mechanistic patterns in the majority of metal systems was first established in elegant isotopic labeling studies, which showed clearly that no intermediate with the symmetry of a cyclobutadiene was involved.In one system, the reaction of a cobaltacyclopentadiene with MeC>2CC CC02Me, benzene formation does not involve direct complexation of the third alkyne to the metal. It has therefore been suggested that the conventional insertion process has been here replaced by a direct Diels-Alder reaction with the metallacycle, perhaps as a result of electronic factors (Scheme 25). o ... 

The structural similarities between S-alkylthiophenium salts and thiophene sulfoxides have prompted the suggestion that both classes are antiaromatic (70JA7610, 70JCS(C)1764). Thiophene sulfoxides are exceptionally reactive, undergoing spontaneous Diels-Alder dimerization unless stabilized by bulky substituents at the 2- and 5-positions. This type of reactivity is reminiscent of cyclobutadiene. In stark contrast to the sulfoxides, S-alkylthiophenium salts show no tendency to take part in Diels-Alder reactions either in an intra- or intermolecular sense. Pentamethylthiophenium hexafluorophosphate (11, X = PFg ) was shown to be completely unreactive toward both electron-rich and electron-deficient dienophiles under conditions where thiophene sulfoxides undergo efficient cycloaddition reactions. 

In the gas phase, 2 is a thermally very stable compound up to 850 °C. Pyrolysis at 880°C/10 Torr generates styrene (55-62%) and o-xylene (6%) along with small amounts of phenylacetylene, benzene, toluene and unidentified hydrocarbons. Cycloaddition reactions with dienophiles were among the first reactivity studies on 2 they were of course driven by the expectation to generate a cyclobutadiene structure by a twofold (4 + 2) cycloaddition. However, while 2 reacts readily with electron-deficient alkenes such as TCNE, A -phenyhnalermide, 4-phenyl-l,2,4-triazolinedione and diethyl azodicarboxylate to form 1 1 adducts 115, a second Diels-Alder reaction... 

The Diels-Alder reaction of hexakis(trifluoromethyl)benzvalene with furan had been reported 63) but not its stereochemistry. We have examined this reaction and found that it proceeds smoothly with many 1.3-dienes if the steric requirement of the olefin is not large in the transition state where exo-attack occurs as confirmed by X-ray analysis (97)96). Therefore, 2,3-dimethylbutadiene reacts smoothly with hexakis(trifluoromethyl)benzvalene whereas 1,3-pentadiene reacts very slowly and 2,4-hexadiene does not at all. The cycloaddition to cyclobutadiene gives a mixture of endo- and exo-adducts (98)97) ... 

In so far as 4//-pyrazoles can be regarded as azadienes, the most obvious method of achieving 3,5-addition would seem to be through a Diels-Alder reaction. Unfortunately, these pyrazoles normally only react in this way with the most reactive dienophiles (4-phenyl-l,2,4-triazole-3,5-dione and cyclobutadiene ). It has recently been shown, however, that under acid catalysis a much wider range of dienophiles can be used, greatly extending the range of cyclopropyl derivatives that can be made. A typical example of an uncatalyzed reaction is that between 4,4-dimethyl-3,5-diphenyl-4i/-pyrazole and cyclobutadiene which yielded, after deazetization, 3,3-dimethyl-2,4-diphenyltricyclo[3.2.0.0 - ]hept-6-ene... 

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