Cycloaddition reactions, solvent effects

Most Diels-Alder reactions, particularly the thermal ones and those involving apolar dienes and dienophiles, are described by a concerted mechanism [17]. The reaction between 1,3-butadiene and ethene is a prototype of concerted synchronous reactions that have been investigated both experimentally and theoretically [18]. A concerted unsymmetrical transition state has been invoked to justify the stereochemistry of AICI3-catalyzed cycloadditions of alkylcyclohexenones with methyl-butadienes [12]. The high syn stereospecificity of the reaction, the low solvent effect on the reaction rate, and the large negative values of both activation entropy and activation volume comprise the chemical evidence usually given in favor of a pericyclic Diels-Alder reaction. 

A strong acceptor TCNE undergoes [2+2] rather than [4+2] cycloaddition reactions even with dienes. 1,1-Diphenylbutadiene [20] and 2,5-dimethyl-2,4-hexadiene (Scheme 5) [21] afford mainly and exclusively vinyl cyclobutane derivatives, respectively. In the reactions of 2,5-dimethyl-2,4-hexadiene (1) the observed rate constant, is greater for chloroform solvent than for a more polar solvent, acetonitrile (2) the trapping of a zwitterion intermediate by either methanol or p-toluenethiol was unsuccessful (3) radical initiators such as benzyl peroxide, or radical inhibitors like hydroquinone, have no effect on the rate (4) the entropies of activation are of... 

The energy and geometry data listed in Table 2.5 show that the effect of solvent bulk (computed for cyclohexane, toluene, diethylether chloroform, THF, and methanol by PCM model), decreases the activation energy, increasing asynchronicity for the [4 + 2] cycloaddition reactions. 

The hetero-Diels-Alder reaction can also employ dienes containing heteroatoms. Cycloaddition of substituted styrenes with di-(2-pyridyl)-1,2,4,5-tetrazine was investigated by Engberts (Eq. 12.56).127 Again, the rate of the reaction increased dramatically in water-rich media. Through kinetic studies, they showed that the solvent effects on the... 

The critical role of the ion-radical pair in the cycloaddition reactions in equation (75) is demonstrated by a careful measurement of the quantum yields as a function of the dienophile concentration and by a study of the effect of solvent and salt on the dynamics of the ion pair ANT+ , MA-. 212 However, in the reported cases, back electron transfer effectively competes with the coupling within the ion-radical pair and thus limits the quantum yields for the formation of the Diels-Alder adduct.212... 

An unusual solvent effect was observed in cycloadditions of aromatic nitrile N-oxides with alkyl-substituted p-benzoquinones in ethanol-water (60 40) the reaction rates were 14-fold greater than those in chloroform (148). The use of ion pairs to control nitrile oxide cycloadditions was demonstrated. A chiral auxiliary bearing an ionic group and an associated counterion provides enhanced selectivity in the cycloaddition the intramolecular salt effect controls the orientation of the... 

A third mechanistically distinct [3 -1- 2] cycloaddition between vinyl ethers and vinyl-carbenoids was discovered and reported in 2001 [26]. This reaction is remarkable because when Rh2(S-DOSP)4 is used as the catalyst, the cis-cyclopentenes 142 are formed in up to 99% enantiomeric excess. The reaction occurs between vinylcarbenoids unsubstituted or alkyl-substituted at the vinyl terminus and vinyl ethers substituted with an aryl or vinyl group. Some illustrative examples are shown in Tab. 14.12. The reaction is considered to be a concerted process, which would be consistent with the highly stereoselective nature of the reaction [26]. Contrary to the [3-1-2] cycloaddition derived by means of vinylogous carbenoid reactivity, this latest [3 -1- 2] cycloaddition is not influenced by solvent effects. Due to steric demands on the carbenoid, the [3-1-2] cycloaddi-tion only occurs with cis-vinyl ethers. 

Another focus of this chapter is the alkynol cycloisomerization mediated by Group 6 metal complexes. Experimental and theoretical studies showed that both exo- and endo- cycloisomerization are feasible. The cycloisomerization involves not only alkyne-to-vinylidene tautomerization but alo proton transfer steps. Therefore, the theoretical studies demonstrated that the solvent effect played a crucial role in determining the regioselectivity of cycloisomerization products. [2 + 2] cycloaddition of the metal vinylidene C=C bond in a ruthenium complex with the C=C bond of a vinyl group, together with the implication in metathesis reactions, was discussed. In addition, [2 + 2] cycloaddition of titanocene vinylidene with different unsaturated molecules was also briefly discussed. 

As an alternative, Firestone proposed a stepwise reaction course for the cycloaddition involving biradical intermediates (Scheme 6.13). This reaction course was based on a number of experimental facts such as small solvent effects as well as the formation of byproducts such as oximes (15,109,110). 

N/L recorded was 16,000 for the reactions using the magnesium aUcoxide of 3-methyl-2-buten-l-ol as a multisubstituted internal allylic alcohol substrate, which is why regiocontrol is still effective in the reactions in a highly coordinating solvent such as THE. Rate enhancement is much lower in the nitrile oxide cycloaddition reactions using homoallylic alcohol substrates. 

---