Transition structures 1,3-dipolar

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. 

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. 

Enhanced reactivity as well as high endo-selectivity based on the rigid transition structure of N-metalated azomethine ylides is attractive for asymmetric 1,3-dipolar cycloaddition reactions. There are several reports known for the design of effective chiral nucleophiles in asymmetric cycloadditions. 

A secondary orbital interaction has been used to explain other puzzling features of selectivity, but, like frontier orbital theory itself, it has not stood the test of higher levels of theoretical investigation. Although still much cited, it does not appear to be the whole story, yet it remains the only simple explanation. It works for several other cycloadditions too, with the cyclopentadiene+tropone reaction favouring the extended transition structure 2.106 because the frontier orbitals have a repulsive interaction (wavy lines) between C-3, C-4, C-5 and C-6 on the tropone and C-2 and C-3 on the diene in the compressed transition structure 3.55. Similarly, the allyl anion+alkene interaction 3.56 is a model for a 1,3-dipolar cycloaddition, which has no secondary orbital interaction between the HOMO of the anion, with a node on C-2, and the LUMO of the dipolarophile, and only has a favourable interaction between the LUMO of the anion and the HOMO of the dipolarophile 3.57, which might explain the low level or absence of endo selectivity that dipolar cycloadditions show. 

AMI calculations have been used to explain the regioselectivities of the intermolecular asymmetric 1,3-dipolar cycloadditions of 2,2-dimethyl-3,4-dihydro-2//-pyrrolc N-oxides with chiral a, /J-unsatu rated esters.96 MO calculations have shown that only in-plane aromaticity is operating in transition structures+associated with the... 

Fig. 6. Transition structures for the 1,3-dipolar cycloadditions of fulminic acid with acetylene (left) and ethene (middle) and of nitrone with ethylene (right)...

Table 5. Transition structure geometries, activation energies, and reaction energies for transition structures of 1,3-dipolar cycloadditions... 

A reaction in the alternative sense 5.133 is the cycloaddition of a nitrile oxide to a terminal alkene, which gives mainly the diastereoisomer 5.141 by way of the transition structure 5.139. Nitrile oxide cycloadditions are among those dipolar cycloadditions which are electrophilic in nature. The substituent A is a hydrogen atom, and the medium-sized group is only a methyl group, so it fits the criteria that make this pathway plausible. 

A highly versatile auxiliary is the Evans oxazolidinone imide (Figure 5.4c, see also Scheme 3.16), available by condensation of amino alcohols [86,87] with diethyl carbonate [86]. Deprotonation by either LDA or dibutylboron triflate and a tertiary amine affords only the Z(0)-enolate. Scheme 5.12 illustrates open and closed transition structures that have been postulated for these Zf0)-enoIates under various conditions, and Table 5.4 lists typical selectivities for the various protocols. The first to be reported (and by far the most selective) was the dibutylboron enolate (Table 5.4, entry 1), which cannot activate the aldehyde and simultaneously chelate the oxazolidinone oxygen [75]. Dipolar alignment of the auxiliary and approach of the aldehyde from the Re face of the enolate affords syn adduct with outstanding diastereoselection, presumably via the closed transition structure illustrated in Scheme 5.12a [75]. The other syn isomer can be formed under two different types of conditions. In one, a titanium enolate is postulated to chelate the oxazolidinone... 

Fig. 10.17. Transition structures for 1,3-dipolar addition of methoxyethene and diazomethane. Structures A1 and B1 correspond to the syn conformation of methoxyethene, whereas A2 and B2 correspond to the anti conformation. The TS with the lowest energy corresponds to the observed product. From J. Chem. Soc., Faraday Trans., 90, 1077 (1994).

The putative polar transition structure finds supporting evidence in the easily ascertainable acceleration of the reaction (see Figs. 16 and 17, and Table 7 in [72e]) with increasing solvent polarity [68], as well as by the structure of monocyclic five-membered ring compounds of type 71 that appear via dipolar intermediates of type W as side-products Scheme 31). 

Cossio et /. studied the aromaticity and regiochemislry of 1,3-dipolar cycloadditions computationally. They investigated the aromaticity of both transition structures and reaction products of the reactions scrutinized via NICS values evaluated at RCPs, which they consider as characterizing rings unambiguously. While the NICS values computed in solution are lower than those obtained in the gas phase, the differences are very smaU. Therefore, aromaticity docs not appear to be very sensitive to solvent effects in the compounds under study. 

Table 1. Gradient and Curvature of the potential energy surfaces at the "concerted transition structure" for cycloaddition reaction of two ethylene molecules, the Diels Alder reaction of Butadiene and ethylene and the 1,3 Dipolar cycloaddition of Fulminic acid and Acetylene.

Ihble 7 Transition-structure Geometries, Activation Energies, and Reaction Energies of Representative 1,3-Dipolar Cycloadditions... 

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