Asynchronous mechanism

Langa et al. [26, 59, 60], while conducting the cycloaddition of N-methylazo-methine ylide with C70 fullerene, proposed a rather similar approach. Theoretical calculations predict an asynchronous mechanism, suggesting that this phenomenon can be explained by considering that, under kinetic control, microwave irradiation will favor the more polar path corresponding to the hardest transition state . 

Theoretical calculations predict an asynchronous mechanism and suggest that the modification of the regiochemical outcome is related to the energies and hardness of the TS involved. Perhaps, in other words, the more polar TS are favored under the action of MW. 

Theoretical calculations have also permitted one to understand the simultaneous increase of reactivity and selectivity in Lewis acid catalyzed Diels-Alder reactions101-130. This has been traditionally interpreted by frontier orbital considerations through the destabilization of the dienophile s LUMO and the increase in the asymmetry of molecular orbital coefficients produced by the catalyst. Birney and Houk101 have correctly reproduced, at the RHF/3-21G level, the lowering of the energy barrier and the increase in the endo selectivity for the reaction between acrolein and butadiene catalyzed by BH3. They have shown that the catalytic effect leads to a more asynchronous mechanism, in which the transition state structure presents a large zwitterionic character. Similar results have been recently obtained, at several ab initio levels, for the reaction between sulfur dioxide and isoprene1. ... 

These experimental secondary deuterium KIEs observed in Diels-Alder reactions have been compared with the respective theoretical KIEs for the stepwise mechanism involving a diradical intermediate (equation 88a) and for concerted synchronous and asynchronous mechanisms (equation 88b) for the Diels-Alder reaction of butadiene with ethylene207. 

As an example of this technique we consider 12C/13C isotope effects in the Diels-Alder condensation of isoprene and maleic anhydride (Equation 7.32). The terminal carbons of isoprene carbons are numbered 1 and 4, the methyl substituted carbon is number 2. The reaction proceeds via a concerted and slightly asynchronous mechanism. 

As predicted by Otis, the method is believed capable of detecting asynchronous mechanical behavior (unequal regional ventilatory time constants), which otherwise can be documented only by the considerably more difficult measurement of dynamic lung compliance. 

Abstract The main computational studies on the formation of (3-lactams through [2+2] cycloadditions published during 1992-2008 are reported with special emphasis on the mechanistic and selectivity aspects of these reactions. Disconnection of the N1-C2 and C3-C4 bonds of the azetidin-2-one ring leads to the reaction between ketenes and imines. Computational and experimental results point to a stepwise mechanism for this reaction. The first step consists of a nucleophilic attack of the iminic nitrogen on the sp-hybridized carbon atom of the ketene. The zwitterionic intermediate thus formed yields the corresponding (3-1 actant by means of a four-electron conrotatoty electrocyclization. The steroecontrol and the periselectivity of the reaction support this two-step mechanism. The [2+2] cycloaddition between isocyanates and alkenes takes place via a concerted (but asynchronous) mechanism that can be interpreted in terms of a [n2s + (n2s + n2s)] interaction between both reactants. Both the regio and the stereochemistry observed are compatible with this computational model. However, the combination of solvent and substituent effects can result in a stepwise mechanism. 

Remarkably, the presence of water showed beneficial effects on both reaction rates and selectivities, while facilitating the iminium ion hydrolysis step in the catalytic cycle. Computational studies suggest an asynchronous mechanism for the reaction [23-25], where the attack of the diene to the / -carbon atom of the iminium ion is the rate-limiting step [23], and the 7r,7r-interaction between the phenyl ring of the catalyst s benzyl group and the olefinic 7r-system of the iminium ion accounts for the selectivity of the reaction [6, 24]. 

Captodative dienes, such as the 2-cyano-l-aza-1,3-butadienes 128 and 129, also undergo hetero Diels-Alder reactions, both inter- and intramolecularly (Scheme 23). Reactivity and regio- and stereo-selectivity in these processes have been accounted for in terms of a concerted asynchronous mechanism involving a diradicaloid transition state [69]. The intramolecular cases illustrated here have been shown to be successful for the preparation of indolizidine 130 and quinolizidine 131 ring systems. 

From these calculations, it is obvious to condude that the first reaction is synchronous with similar bond lengths formed whereas the second one is asynchronous with quite different bond lengths formed. Furthermore, the dipole moments remained the same for GS and TS in the first reaction whereas they are noticeably increased in the TS for the second. All these conclusions strongly support the evidence and interpretation of important spedfic not purely thermal MW effects when asynchronous mechanisms are involved. 

MW effects can therefore act as a useful tool enabling appreciation of the asynchronicity of TS. This is especially true of 1,3-dipolar cycloadditions (cf. Chapter 11) [76]. Because these reactions are well-known to proceed via asynchronous mechanisms, MW-specific effects are expected, and were often apparent when MW and A were seriously checked under similar sets of conditions [77, 78]. A specific case is illustrated here (Fig. 4.10) [79]. 

Conventional ab initio methods have been used in the study of reactions of unsymmetrical dienes and/or dienophi-les. These calculations predict concerted asynchronous mechanisms. The values of the potential energy barriers are very sensitive to the level of calculation, and reasonable values are only obtained when electron correlation is included up to the MP3 level. DFT calculations also predict concerted mechanisms, the transition states being more asynchronous than those obtained at the HF or MP2 levels. The potential energy barriers obtained with GGA and hybrid functionals are in excellent agreement with those obtained with high level ab initio methods. ... 

Computational studies of this rearrangement suggest that the reaction may proceed via a concerted but highly asynchronous mechanism or even via a stepwise mechanism [141]. It has been proposed that both protonation of the nitroso acetal and the use of a polar solvent should accelerate this transformation. This proposal is consistent with the observed acceleration of the rearrangement on silica gel. 

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