Cycloaddition reactions asynchronous

In an investigation by Yamabe et al. [9] of the fine tuning of the [4-1-2] and [2-1-4] cycloaddition reaction of acrolein with butadiene catalyzed by BF3 and AICI3 using a larger basis set and more sophisticated calculations, the different reaction paths were also studied. The activation energy for the uncatalyzed reaction were calculated to be 17.52 and 16.80 kcal mol for the exo and endo transition states, respectively, and is close to the experimental values for s-trans-acrolein. For the BF3-catalyzed reaction the transition-state energies were calculated to be 10.87 and 6.09 kcal mol , for the exo- and endo-reaction paths, respectively [9]. The calculated transition-state structures for this reaction are very asynchronous and similar to those obtained by Houk et al. The endo-reaction path for the BF3-catalyzed reaction indicates that an inverse electron-demand C3-0 bond formation (2.635 A... 

The theoretical investigations of Lewis acid-catalyzed 1,3-dipolar cycloaddition reactions are also very limited and only papers dealing with cycloaddition reactions of nitrones with alkenes have been investigated. The Influence of the Lewis acid catalyst on these reactions are very similar to what has been calculated for the carbo- and hetero-Diels-Alder reactions. The FMOs are perturbed by the coordination of the substrate to the Lewis acid giving a more favorable reaction with a lower transition-state energy. Furthermore, a more asynchronous transition-structure for the cycloaddition step, compared to the uncatalyzed reaction, has also been found for this class of reactions. 

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. 

Cycloaddition reactions are a very important class of pericyclic reactions in which two unsaturated molecules join by converting two tt-bonds into two new a-bonds between their termini. Although cycloaddition reactions are concerted (no intermediate species are formed), the two new bonds in a few cases may be formed in an asynchronous fashion. Depending on partial charge distribution in both reactants, the formation of one bond may lead to the development of the other. 

An additional important result follows from rule (a). It seems that in polar cycloaddition reactions the most electrophilic reagent control the asynchronicity of the process by a larger bond formation process at the most electrophilic site of the electron acceptor. This result may be traced to the more prevalent role of the electron acceptor in the electrophile/nucleophile interaction, which follows from the extra work associated with the redistribution of the electronic charge that it takes from the nucleophilic partner. The local electrophilicity counterpart, on the other hand, consistently predicts the regiose-lectivity expected in DA and 1,3-dipolar cycloadditions. 

Captodative alkenes are also good dipolarophiles [65] and dienophiles [66]. The corresponding [3+2] and [4+2] cycloaddition reactions seem to be concerted, as usual, so that diradicals are not directly involved as such. However, the mechanism may be rather asynchronous, with the transition state having pronounced di-radicaloid character, and thereby being stabilized by the captodative effect [67]. This can explain the higher dienophilic character of a-methylthioacrylonitrile 127 compared to acrylonitrile, despite the unfavorable steric effect (Scheme 22) [68]. 

The bond order uniformity for the transition state with those heterocycles is not an adequate approach for evaluation of their reactivity because their transition state structures are highly asynchronous. Therefore, we have evaluated their reactivity by estimating the activation barriers for the cycloaddition reactions with acetylene, ethylene, and cyclopropene as dienophiles (Table 39). All computed activation barriers were very high and are not expected to be experimentally feasible. That is fully supported by the fact that, at this moment, there is no experimental evidence that five-membered heterocycles with... 

These equations were used subsequently to account for the thermal and photochemical dimerization of butadiene, the Diels-Alder addition between two acrolein molecules, where the asynchronous nature of the cycloaddition was demonstrated, and the endo mechanism. These equations provided a demonstration of the symmetry rules for the cycloaddition reactions, and could account for the photodimerization of trop-one. 

Fig.l Schematic representation of 3 energy diagrams which will be used to discuss synchronous vs asynchronous bond formation in cycloaddition reactions. 

The conclusion as to the nonconcerted character of the [4 -h 2]-cycloaddition reactions and sharp asynchronization of the process of formation of the -bonds in the course of the reaction has been borne out by a careful kinetical analysis, performed by Dewar, of reactions of typical dienophile maleic anhydride with a number of furane derivatives as well as by critical examination of other experimental data on the Diels-Alder reactions [29,35]. A similar conclusion has also been drawn for the [4 + l]-cycloaddition reaction [31], for some other... 

A transannular 4 + 2-cycloaddition initiates the tandem 4 + 2/3+2-cycloaddion cascade of 1,3,4-oxadiazoles (1) to yield cycloadduct intermediates (2) used for the synthesis of analogues of vinblastine (Scheme 1)." The multi-component 4+ 2/3+2-domino cycloaddition reactions of 3-nitroindole derivatives with vinyl ethers and acrylates were studied computationally and experimentally. The 4+2-reaction follows a classical concerted asynchronous process while the 3 + 2-addition involves an electron donation by an electron-deficient reaction partner. ... 

The catalytic asymmetric /-selective Diels-Alder annulation of a, -unsaturated /-butyrolactams with enones provided a synthesis of, y-functionalized bridged bi-or tri-cyclic dihydropyranopyrrolidin-2-ones in one step (up to 98% yield, >20 1 dr, and 99% ee) The inverse-electron-demand aza-Diels-Alder cycloaddition 0 of A-aryl-a,/0-unsaturated ketimines with enecarbamates in the presence of chiral bifunctional phosphoric acids produced 4,5,6-trisubstituted 1,4,5,6-tetrahydropyridines having three contiguous stereogenic centres in up to 84% yield, 95 5 dr, and 95% 5-Alkenylthiazoles react as in-out dienes with e-poor dienophiles in polar 44-2- 0 cycloaddition reactions. The cycloadditions are site selective. The mechanism is thought to lie between a concerted but highly asynchronous process and a stepwise process. 

In a recent theoretical study of the reaction of 1 -aza-2-azoniaallene salts, with isocyanates it was concluded that these reactions proceed in asynchronous but concerted pathways. The presence of chloro groups in the l-aza-2-azoniaallene salts, as well as methyl groups in the isocyanates, favor the cycloaddition reactions . 

The [3+2] cycloaddition reactions of isocyanates with 1 -aza-2-azoniaallene salts proceed by an asynchronous concerted mechanism . 

Honk et al. concluded that this FMO model imply increased asynchronicity in the bond-making processes, and if first-order effects (electrostatic interactions) were also considered, a two-step mechanisms, with cationic intermediates become possible in some cases. It was stated that the model proposed here shows that the phenomena generally observed on catalysis can be explained by the concerted mechanism, and allows predictions of the effect of Lewis acid on the rates, regioselectivity, and stereoselectivity of all concerted cycloadditions, including those of ketenes, 1,3-dipoles, and Diels-Alder reactions with inverse electron-demand [2],... 

The kinetic data for cycloadditions of 2,4,6-trimethylbenzonitrile oxide to benzonitriles are consistent with a concerted although asynchronous reaction with a transition state, in which the formation of the O—C bond is more advanced than the making of the C—N bond <90JCS(P2)245>. 

Several computational studies have addressed whether the dipolar cycloaddition of nitronates is a concerted or stepwise process (93,100). Natural population analysis reveals that their is very little zwitterionic character in the transition state. The formation of the C C bond marginally precedes the C—O bond on the basis of calculated bond lengths and orders in the transition structure. These calculations also show that the reaction is a concerted process that is shghtly asynchronous. In addition, the cycloaddition likely proceeds through an early transition state and is overall an exothermic process. 

The stereochemistry of ketene to alkcne cycloadditions is such that retention of the alkene configuration is observed. Furthermore, in cycloadditions with unsymmetrically substituted ketenes the larger of the two ketene substituents ends up as with respect to the adjacent alkene substituent (or eiulo in cycloalkene cycloadditions). This stereochemical outcome was originally attributed to the concerted [ff2a + n2a] nature of kctcnc to alkene cycloadditions,21 although more recent experimental and theoretical evidence indicate that these reactions are asynchronous and in some cases in which polarized double bonds are involved actual zwittcrions may be intermediates.9 1195 Also in certain cases the endo product in ketene to alkene cycloadditions may be the thermodynamic product from equilibration studies.22,23 Nevertheless, stereochemical control can be achieved in most such reactions as shown by the examples of 12,24 13,29 14,25 15,26 16,27 and 17.28... 

The cycloaddition of formaldehyde and ketene has been studied by ab initio methods.22 A two-step zwitterionic mechanism is suggested for dichloromethane solvent, while the gas-phase reaction is concerted but asynchronous. 

Ab initio calculations indicate that in the gas phase the reaction of ketene inline and formaldehyde is concerted but asynchronous whereas in dichloromethane it is a two-step zwitterionic reaction.38 The 2 + 2-cycloadditions of keteniminium triflates with imines yields 2-azetidiniminium salts with cis stereoselectivity.39 The intramolecular 2 + 2-cycloaddition of ketenimines with imines (24) provides a novel synthesis of azeto[2,l-Z>]quinazolines (25) (Scheme 9).40... 

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. 

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