Uncatalyzed thermal cycloaddition reaction

Transition metal-catalyzed [4+ 2]-cycloadditions ofdiene-allenes 247 can lead to different results. With a nickel catalyst Wender et al. isolated the anellated system of two six-membered rings 248 with a rhodium catalyst the anellation of a five- and a six-membered ring 249 was possible (Scheme 15.78) [149]. Both transformations proceed readily at low temperatures whereas the uncatalyzed thermal reaction requires 185 °C. Even an anellation of a six- and a seven-membered ring was achieved. 

Several of these cyclopropylacetylenes constitute convenient substrates for catalyzed or uncatalyzed cycloaddition reactions. For instance, the methyl 3-[l-chlorocyclo-propyl]propiolate 66 is a reasonably reactive dienophile which underwent thermal reaction with various 1,3-dienes to yield [2 + 4] cycloadducts, such as 67, Eq. (20) 20). 

Bauld and coworkers, especially, developed the analogous Diels-Alder (4 + 2) cycloaddition reactions. These reactions are conveniently catalyzed by tris(4-bromophenyl)aminium hexachloroantimonate (78) or by photosensitization with aromatic nitriles. The radical cation-catalyzed Diels-Alder reaction is far faster than the uncatalyzed one, and leads to some selectivity for attack at the least substituted double bond for the monoene component (Scheme 18, 79 —> 80), but only modest endo selectivity (e- and x-80) [105]. Cross reactions with two dienes proved to be notably less sensitive to inhibition by steric hindrance of alkyl groups substituted on the double bonds than the uncatalyzed reactions, as cyclohexadiene adds detectably even to the trisubstituted double bond of 2-methylhexadiene (82), producing both 83 and 84. Dienes such as 85 react with donor-substituted olefins (86) to principally give the vinylcyclobutene products 87, but they may be thermally rearranged to the cyclohexene product 88 in good yield [105]. Schmittel and coworkers have studied the cation radical catalyzed Diels-Alder addition of both... 

The problems are due to the electrophilicity of the metal-carbene intermediates in these transformations, and to competitive, fast dihydropyrazole formation resulting from uncatalyzed thermal [3 + 2] cycloaddition of the diazo compound to the alkene furthermore, o , -unsaturated nitriles often yield 2-vinyloxazoles under the reaction conditions. 

Direct Wittig reaction of Ph PCHCOn,Me with the four unsubstituted D-aldopentoses followed by acetylation provides convenient preparative access to acyclic seven-carbon trans-2.3-unsaturated sugar derivatives. These products served as dienophiles for a detailed comparative study in Diels—Alder cycloaddition with cyclopentadiene. Related syntheses afforded analogous cis-dienophiles. Cycloaddition under uncatalyzed thermal conditions gave mixtures of the four possible stereoisomeric norbornene adducts. The endo, exo ratios, and diastereofacial selectivities of the adducts were determined by NMR spectroscopy and by chemical transformations, supplemented by selected X-ray crystallographic analyses. Different distributions of isomers were encountered when a Lewis acid was used to catalyze the cycloaddition. The reaction can be controlled to provide preparative access to selected isomers and thus constitutes a versatile method for chirality transfer from the precursor sugar to four new asymmetric centers in a carbocyclic framework. 

Based on a detailed investigation, it was concluded that the exceptional ability of the molybdenum compounds to promote cyclopropanation of electron-poor alkenes is not caused by intermediate nucleophilic metal carbenes, as one might assume at first glance. Rather, they seem to interfere with the reaction sequence of the uncatalyzed formation of 2-pyrazolines (Scheme 18) by preventing the 1-pyrazoline - 2-pyrazoline tautomerization from occurring. Thereby, the 1-pyrazoline has the opportunity to decompose purely thermally to cyclopropanes and formal vinylic C—H insertion products. This assumption is supported by the following facts a) Neither Mo(CO)6 nor Mo2(OAc)4 influence the rate of [3 + 2] cycloaddition of the diazocarbonyl compound to the alkene. b) Decomposition of ethyl diazoacetate is only weakly accelerated by the molybdenum compounds, c) The latter do not affect the decomposition rate of and product distribution from independently synthesized, representative 1-pyrazolines, and 2-pyrazolines are not at all decomposed in their presence at the given reaction temperature. 

Interestingly, the uncatalyzed reaction takes place at 80°C and is a rare case of a thermal [2+2] cycloaddition. However, the catalytic process offers advantages in terms of higher cis/trans ratios. It should be noted that the turns isomer can be isomerized into the thermodynamically favored cis product by extended heating to 80°C in acetonitrile. The utility of the products was demonstrated by the synthesis of amino acid 20 (Scheme 2.6). 

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