Asynchronous cycloaddition

The predominant formation of the endo-isomers 50-A and 50-B can be explained as follows. Based on the concept of "concerted but asynchronous" cycloaddition, Roush stated that a 1,7,9-decatriene system possessing an electron-withdrawing group at the terminal position of the dienophile part can generally adopt a six-membered chair-like transition state while a six-membered boat-like transition state may be occasionally favored depending on the kind of substituents [45, 46]. It seems reasonable to apply the six-member transition state model to our substrate 48. Therefore, four chair-like transition states TS-Chair-A to TS-Chair-D and four boat-like transition states TS-Boat-A to TS-Boat-D are possible (Fig. (5)). All boat-like transition... 

Such important differences in reactivity have been rationalized using MO/ionization potential considerations [92JCS(D)859 93JCS(D)1499], With both NC.CN and [C(CN)3], an important step in the reaction pathway would appear to be an electrostatic interaction between SNS+ and the heterocyclic nitrogen in the intermediate 1,3,2,4-dithiadiazolyl/lium (bound to carbon), leading to (i) modification of orbital energies and (ii) an asynchronous cycloaddition mechanism (see Section XII.B). 

Several mechanistic variations might be possible under either of the main options (1 or 2). For example, the four-center process might involve a direct conversion from the P=C and the C=0 reactants into the oxaphosphetane (asynchronous cycloaddition) (18,59,66,219,220). In this case, there would be no other intermediates and no energy minima between the reactants and... 

The concerted asynchronous cycloaddition mechanism involving a four-centered transition state was suggested to be operating in these systems. 

The detection of oxaphosphetanes as relatively stable Wittig intermediates led to revision of the reaction mechanism theory. An asynchronous cycloaddition between ylide and carbonyl component was proposed for the oxaphosphetane formation a transition state resembling the starting material in the case of reactive ylides and a transition state resembling oxaphosphetane in the case of moderate and stable ylides can explain the different (E/Z)-selectivities of the different ylide types [44]. 

The reaction shows characteristics of potentially being a cmiceited, albeit asynchronous, cycloaddition. Thus, comparing the E and Z enoates 6 and 7... 

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],... 

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 orbital interaction depicted in Scheme 1.15 shows that the two cr-bonds form at the same time but do not develop to the same extent. The Diels-Alder cycloaddition of unsymmetrical starting materials is therefore concerted but asynchronous. A highly unsymmetrical diene and/or dienophile give rise to a highly unsymmetrical transition state and a stepwise pathway can be followed. 

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. 

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 . 

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. 

In contrast, the [2+2] cycloaddition between alkenes and isocyanates is in general concerted (although highly asynchronous) and consists of [n2s + (n2s + k2s) mechanism rather than a [n2s + n2a] process. The polarity of the transition... 

---