Ethylene cycloaddition reactions

Contrast the Diels-Alder reaction with a cycloaddition reaction that looks superfl cially similar the combination of two ethylene molecules to give cyclobutane... 

Refer to the molecular orbital diagrams of allyl cation (Figure 10 13) and those presented earlier in this chapter for ethylene and 1 3 butadiene (Figures 10 9 and 10 10) to decide which of the following cycloaddition reactions are allowed and which are forbidden according to the Woodward-Floffmann rules... 

A large number of pyridazines are synthetically available from [44-2] cycloaddition reactions. In one general method, azo or diazo compounds are used as dienophiles, and a second approach is based on the reaction between 1,2,4,5-tetrazines and various unsaturated compounds. The most useful azo dienophile is a dialkyl azodicarboxylate which reacts with appropriate dienes to give reduced pyridazines and cinnolines (Scheme 89). With highly substituted dienes the normal cycloaddition reaction is prevented, and, if the ethylenic group in styrenes is substituted with aryl groups, indoles are formed preferentially. The cycloadduct with 2,3-pentadienal acetal is a tetrahydropyridazine derivative which has been used for the preparation of 2,5-diamino-2,5-dideoxyribose (80LA1307). 

Cycloaddition involves the combination of two molecules in such a way that a new ring is formed. The principles of conservation of orbital symmetry also apply to concerted cycloaddition reactions and to the reverse, concerted fragmentation of one molecule into two or more smaller components (cycloreversion). The most important cycloaddition reaction from the point of view of synthesis is the Diels-Alder reaction. This reaction has been the object of extensive theoretical and mechanistic study, as well as synthetic application. The Diels-Alder reaction is the addition of an alkene to a diene to form a cyclohexene. It is called a [47t + 27c]-cycloaddition reaction because four tc electrons from the diene and the two n electrons from the alkene (which is called the dienophile) are directly involved in the bonding change. For most systems, the reactivity pattern, regioselectivity, and stereoselectivity are consistent with describing the reaction as a concerted process. In particular, the reaction is a stereospecific syn (suprafacial) addition with respect to both the alkene and the diene. This stereospecificity has been demonstrated with many substituted dienes and alkenes and also holds for the simplest possible example of the reaction, that of ethylene with butadiene ... 

How do orbital symmetry requirements relate to [4tc - - 2tc] and other cycloaddition reactions Let us constmct a correlation diagram for the addition of butadiene and ethylene to give cyclohexene. For concerted addition to occur, the diene must adopt an s-cis conformation. Because the electrons that are involved are the n electrons in both the diene and dienophile, it is expected that the reaction must occur via a face-to-face rather than edge-to-edge orientation. When this orientation of the reacting complex and transition state is adopted, it can be seen that a plane of symmetry perpendicular to the planes of the... 

When the orbitals have been classified with respect to symmetry, they can be arranged according to energy and the correlation lines can be drawn as in Fig. 11.10. From the orbital correlation diagram, it can be concluded that the thermal concerted cycloadditon reaction between butadiene and ethylene is allowed. All bonding levels of the reactants correlate with product ground-state orbitals. Extension of orbital correlation analysis to cycloaddition reactions involving other numbers of n electrons leads to the conclusion that the suprafacial-suprafacial addition is allowed for systems with 4n + 2 n electrons but forbidden for systems with 4n 7t electrons. 

Analogously, the 1,3-dipolar cycloaddition reaction of 2-diazopropane with propargyl alcohol 62b, performed at 0 °C in dichloromethane, was completed in less then 10 h and led to a monoadduct 63b with the same regioselective addition mode of 59 to the triple bond. The HMBC spectrum showed correlations between the ethylenic proton and the carbons C3 and C5 and between the methyl protons and the carbons C3 and C4. 

This regioselectivity is practically not influenced by the nature of subsituent R. 3,5-Disubstituted isoxazolines are the sole or main products in [3 + 2] cycloaddition reactions of nitrile oxides with various monosubstituted ethylenes such as allylbenzene (99), methyl acrylate (105), acrylonitrile (105, 168), vinyl acetate (168) and diethyl vinylphosphonate (169). This is also the case for phenyl vinyl selenide (170), though subsequent oxidation—elimination leads to 3-substituted isoxazoles in a one-pot, two-step transformation. 1,1-Disubstituted ethylenes such as 2-methylene-1 -phenyl-1,3-butanedione, 2-methylene-1,3-diphenyl- 1,3-propa-nedione, 2-methylene-3-oxo-3-phenylpropanoates (171), 2-methylene-1,3-dichlo-ropropane, 2-methylenepropane-l,3-diol (172) and l,l-bis(diethoxyphosphoryl) ethylene (173) give the corresponding 3-R-5,5-disubstituted 4,5-dihydrooxazoles. 

Fields et alf and Schmidt made closely parallel observations concerning polar cycloaddition of ethylenes substituted at the a-position by an electron-withdrawing group and having no substituent at the jS-position. In both cases the product observed was that to be expected if the electrophile had added to the j3-carbon atom. Since it is clear that the normal ground-state polarization of acrylonitrile (127) and methyl methacrylate (128) should tend to destabilize the cation produced by j8-addition, it was concluded that the orientation of polar cycloadditions could not be predicted by the rules of electrophilic addition and that this apparent anomaly pointed toward a more concerted type of cycloaddition reaction. 

Maprotiline Maprotiline, iV-methyl-9,10-ethanoanthracen-9(10H)-propylamine (7.1.22), is synthesized by a 4-1-2 cycloaddition reaction of 9-(3-methylaminopropyl)anthracene with ethylene [39 1]. 

The cycloaddition reactions of isoquinolinium species produce fused isoquinoline products. The Af-ylide of 53, formed with base addition, couples with alkenes <99S51> or imines <99T7279> to afford tricyclic products, such as 54. Pyrrole-fused isoquinolines result from the reaction between mUnchnone imine intermediates and a,yff-ethylenic esters <99EJOC297>. N-Arylimides undergo 1,3-dipolar cycloaddition with strained frani-cyclooctenes, as opposed to common cycloalkenes, to tdford the pyrazolidine-fused ring system <99H(50)353>. 

Benzil undergoes a cycloaddition reaction with stilbene and 1,1-diphenyl-ethylene to form adducts containing the 2,3-dihydro-[l,4]-dioxin ring system and with visnagin to form an oxetane. These reactions and the cycloaddition reactions of the analogous o-quinones are reviewed by Schonberg.87... 

S. Precursor mediated cycloaddition reaction of ethylene to the Si(100)c(4 x 2) surface. Journal of the American Chemical Society 126, 9922 (2004). 

The concept of the conservation of orbital symmetry can be extended to intermolecular cycloaddition reactions which occur in a concerted manner. The simplest case is the dimerization of ethylene molecules to give cyclobutane, the 2n + 2je cycloaddition. The proper geometry for the concerted action would be for the two ethylene molecules to orient one over the other. Two planes of symmetry are thereby set up -perpendicular to the molecular plane bisecting the bond axes oy-parallel to the molecular plane lying in between the two molecules (Figure 8.10). 

Recently, substantial progress in stereochemistry of the cycloaddition reaction has been reported [34], Cycloaddition between optically active oxadiene 13 and l-acetoxy-2-ethoxy-ethylene, promoted by dimethylaluminum chloride, leads to dihydropyran 14, with a very high endo-exo stereoselectivity (54 1) and in an almost quantitative yield (see Scheme 6). When trimethylsilyl triflate was used as the promoter in this reaction, the reverse endo-exo selectivity (1 5) has been noted. The dihydropyrans obtained served as substrates for the synthesis of (3-d- and 3-L-mannopyranosides [34]. 

Cycloaddition reactions have been used for the transformation of [3.3.3]cyclazine derivatives. DMAD in boiling benzene converted (265c) into the red Diels-Alder adduct (281a). This readily formed a dihydro derivative (281b), which lost ethylene above 220 °C to give... 

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