Methyl acrylate 1,3-dipoles

There are probably several factors which contribute to determining the endo exo ratio in any specific case. These include steric effects, dipole-dipole interactions, and London dispersion forces. MO interpretations emphasize secondary orbital interactions between the It orbitals on the dienophile substituent(s) and the developing 7t bond between C-2 and C-3 of the diene. There are quite a few exceptions to the Alder rule, and in most cases the preference for the endo isomer is relatively modest. For example, whereas cyclopentadiene reacts with methyl acrylate in decalin solution to give mainly the endo adduct (75%), the ratio is solvent-sensitive and ranges up to 90% endo in methanol. When a methyl substituent is added to the dienophile (methyl methacrylate), the exo product predominates. ... 

For acyclic nitronates, the reaction rate can depend on the configuration of the dipole. On the basis of 15N NMR spectroscopic data, it was demonstrated (338a) that thermodynamically more favorable lruns isomers of nitronates (1) are much less reactive in [3+ 2]-addition to methyl acrylate (Scheme 3.128). 

However, treatment of the precursor 74, where there is no substitution at C(4) (i.e., R = Me) led to a single [3+2] cycloadduct 75 with methyl acrylate. The unstable oxazolines 75, are considered to open spontaneously to their valence bond, 1,3-dipole tautomers 76, which are trapped in situ by the dipolarophile. Use of DMAD led to the formation of the expected 2,5-dihydropyrrole (77), but difficulties in isolation required DDQ aromatization to pyrrole 78 (Scheme 3.19). 

Cyclopropyl aldehydes.2 The reagent is a more reactive 1,3-dipole than alkyl dia/oacctatcs. It reacts with various olelins such as styrene, methyl acrylate, and 2 to form pyrazolincs a, which on photolysis arc converted into the cyclopropyl acelals b. The free aldehydes (3) are obtained by acid hydrolysis in overall yields greater than 80%. 

Imidate-derived dipoles have played a prominent role in the synthesis of the pyrrolizidine alkaloid retronecine (121).119 The imidate salt derived from lactam (118) was found to undergo a smooth desilylation reaction to produce azomethine ylide (119). Trapping of this dipole with methyl acrylate affords... 

Hydrazones have also been used as azomethine imine precursors to achieve cycloadditions.157 Proto-nated hydrazones act under suitable conditions as quasi-azomethine imines in polar [3+ + 2] cycloadditions. Thus, r.cetaldehyde phenylhydrazone (201) was found to react with styrene in the presence of sulfuric acid in a regiospecific manner to give pyrazolidine (203 Scheme 47) as a diastereomeric mixture.157 The most commonly used azomethine imine has a phenyl group attached to one end of the dipole and hence has a raised HOMO relative to the unsubstituted system. Because the coefficients at the terminal atoms of the dipole are smaller in the LUMO than they are in the HOMO, the phenyl group does not lower the energy of the LUMO as much as it raises the energy of the HOMO. With electron-deficient di-polarophiles like methyl acrylate, the reaction is dipole HOMO-controlled, and mixtures can be expected. In fact, a 1 1 mixture of regioisomers was obtained in the reaction of (201) with acrylonitrile (equation 9).157... 

Similarly, nitrile oxides react with methyl acrylate 2.42 to give the adduct 2.43 with the substituent on C-5 and terminal alkenes also react in this way to place the alkyl group on C-5. Many dipoles react well with electron-rich dipolarophiles, but not with electron-poor dipolarophiles. Other dipoles are the other way round. To make matters even more complex, the presence of substituents on the dipole can change these patterns and impart their own regioselectivity. Thus the carbonyl ylid reaction 2.45 has a well defined regiochemistry determined only by the substituents, since the core dipole is symmetrical. This reaction also illustrates the point that dipolarophiles do not have to be alkenes or alkynes—they can also have heteroatoms. 

In order to form the activated complex required for the formation of product D, rotational changes of the less dipolar anti-form A to the more dipolar s jn-conformer B are necessary, to give an activated complex C with more parallel bond dipoles, which is thus more dipolar and better solvated than the reactant molecule. In agreement with this explanation is the observation that the reverse refro-Diels-Alder reaction exhibits no large solvent effect, since the activated complex C is quite similar to the reactant D [807], A very subtle solvent effect has been observed in the Diels-Alder addition of methyl acrylate to cyclopentadiene [124], The polarity of the solvent determines the ratio of endo to exo product in this kinetically controlled cycloaddition reaction, as shown in Eq. (5-43). The more polar solvents favour endo addition. 

Lastly, it should be mentioned that using 3 the synthesis of the only known purely organic nitrilimine 13 (90 % yield) was possible [13]. To illustrate the importance of this type of 1,3-dipole in heterocyclic synthesis, note that nitrilimine 13 undergoes regio-, stereo-, and even diastereo-selective [2+3]-cycloadditions [13, 15] with methyl acrylate, methylpropionate, dimethyl fiimarate. 

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