Dipolarophiles with ethene

Diazomethane is an electron-rich 1,3-dipole, and it therefore engages in Sustmann type I 1,3-dipolar cycloadditions. In other words, diazomethane reacts with acceptor-substituted alkenes or alkynes (e.g., acrylic add esters and their derivatives) much faster than with ethene or acetylene (Figure 12.33). Diazomethane often reacts with asymmetric electron-deficient dipolarophiles with orientation selectivity, as exempli-... 

Heterocycles Both non-aromatic unsaturated heterocycles and heteroaromatic compounds are able to play the role of ethene dipolarophiles in reactions with nitrile oxides. 1,3-Dipolar cycloadditions of various unsaturated oxygen heterocycles are well documented. Thus, 2-furonitrile oxide and its 5-substituted derivatives give isoxazoline adducts, for example, 90, with 2,3- and 2,5-dihydro-furan, 2,3-dihydropyran, l,3-dioxep-5-ene, its 2-methyl- and 2-phenyl-substituted derivatives, 5,6-bis(methoxycarbonyl)-7-oxabicyclo[2.2.1]hept-2-ene, and 1,4-epoxy-l,4-dihydronaphthalene. Regio- and endo-exo stereoselectivities have also been determined (259). 

R = Me) under standard generation conditions, in the presence of activated alkene dipolarophiles led to the expected adducts (Scheme 3.49). In the case of trans-l-nitro-2-(3,4-methylenedioxyphenyl) ethene, a 3 2 mixture of diastereoisomers was isolated. Replacement of the methyl group with a methyl ether (R = CH20Me),... 

Ess and Houk applied this model to 1,3-dipolar cycloadditions to ethene and ethyne. B3LYP/6-31G(d) and CBS-QB3 computations were carried out for the reactions of nine 1,3-dipoles shown in Scheme 4.3. The activation energies of these 18 reactions do not correlate with the reaction energies thus, there is no correlation to the effect that the more exothermic is the reaction, the lower will be its activation barrier. Rather, the activation energies correlate extremely well with the distortion energy (r = 0.97). Ess and Houk argue that the TS is achieved when the t-orbitals of the dipole align well with the jc-orbitals of the dipolarophile. This... 

From a synthetic viewpoint, iV-arylvinylamines are not appropriate as azomethine ylide precursors because the hydrogen shift from the intermediary ylides must be extremely accelerated by the rearomatization of the fused dihydro benzo moiety. Zaima and Mitsuhashi were the first to succeed with synthetic applications of the above photochemical generation method of cyclic azomethine ylides (83JHC1). The substrate employed in their work is bis(l-methoxycarbonylvinyl)amine. Irradiation of this divinylamine in carbon tetrachloride at 18°C in the presence of acetylenedicarboxylates produces excellent yields of 7-azabicyclo[2.2.1]hept-2-ene-l,2,3,4-tetracarboxylates 172, which correspond to the cycloadducts of the expected azomethine ylide intermediate 171. Heating the bicyclic cycloadducts 172 at 90-120°C induces a smooth cycloreversion eliminating a molecule of ethene to give pyrrole-2,3,4,5-tetracarboxylates in quantitative yields. The azomethine ylide 171 can be trapped also with olehnic dipolarophiles, such as maleates and fuma-rates, to furnish stereospecifically 7-azabicyclo [2.2.1] heptane-1,2,3,4-tetra-carboxylates 173 and 174, respectively (84JHC445). 

In another study, the role of dipolarophile substituents on reactivity was assessed using disubstituted ethenes with the nitrile ylide 1,3-dipole. A DFT (B3LYP/6-31G ) study examined and the degree of synchronicity as a function of substituent electronic character. The reaction had successively smaller and less synchronicity as the substituent became more electron attracting in the order CH3 < Cl < OH < C=N < N=0.i 4... 

This investigation opened the way to further two-step cycloadditions of the thiocarbonyl ylide 6.23 with other electrophilic alkenes, e.g., with l,2-dicyano-l,2-bis(trifluoromethyl)ethene (Huisgen et al., 1989). Both the latter dipolarophile and tetracyanoethene demonstrated that, besides the 1,3-dipolar addition product 6.28, the cyclic ketene imine 6.29 is formed in a reversible 1,7-ring closure (6-18, Huisgen et al., 1986b, 1989). 

If the dipolarophile is assymmetric (d e in d=e. Sect. 6.2, Scheme 6-5), there are two alternatives for the diazoalkane and all other unsymmetrical 1,3-dipoles in their cycloadditions with that dipolarophile. For example, diazomethane and an ethene derivative with an alkyl substituent R may yield the 3- or the 4-alkyl-l-pyrazolines (6-19), or a mixture of both. These primary products rearrange at higher temperature or in the presence of base to give the corresponding alkyl-2-pyrazolines. 

Those reactions with unsubstituted ethene and with its derivatives containing a conjugated (e.g., CH2 = CH- in butadiene) or an electron-withdrawing substituent are controlled by the HOMO(dipole) - LUMO(dipolarophile) overlap, those with electron-rich dipolarophiles (e. g., ethoxyethene) are predicted to follow clearly the reverse overlap, and in alkyl-substituted ethenes both modes are approximately equally important. 

Buchner accomplished the first synthesis of pyrazole by a cycloaddition in 1889, but not by the direct reaction of diazomethane and ethyne, but with methyl diazoacetate and an electron-deficient dipolarophile, ethynedicarboxylate (see Sect. 6.2). Unsubstituted ethene and ethyne were considered for a very long time to be not sufficiently reactive for synthetic purposes, although von Pechmann (1898 b) had reported a 50 0 yield of pyrazole from diazomethane and ethyne shortly after the discovery of diazomethane. The knowledge of diazomethane being explosive is probably the reason that the obvious advantage of a reaction under pressure in order... 

The solvent could have a great impact on the reaction mechanism, as one study demonstrates, using substituted ethenes (E-l,2-di(alkylsulfonyl)-l,2-dichloroethene) as dipolarophiles (Figure 7). In aprotic solvents, the reaction takes place as a 1,3-dipolar cycloaddition, with... 

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