Transition state from semiempirical calculations

The acyclic precursor is an oc, 3-unsaturated amido aldehyde that was condensed with iV-methylhydroxylamine to generate the nitrone ( )-48, which then underwent a spontaneous cycloaddition with the alkene to afford the 5,5-ring system of the isoxazolidinyl lactam 47. The observed product arises via the ( )-nitrone transition state A [or the (Z)-nitrone equivalent] in which the position of the benzyl group ot to the nitrone effectively controls the two adjacent stereocenters while a third stereocenter is predicted from the alkene geometry. Both transition states maintain the benzyl auxiliary in an equatorial position and thus avoid the unfavorable 1,3-diaxial interaction with the nitrone methyl or oxygen found in transition state B. Semiempirical PM3 calculations confirm the extra stability, predicting exclusive formation of the observed product 47. Related cycloadducts from the intramolecular reaction of nitrones containing ester- rather than amide-tethered alkene functionality are also known (83-85). 

A number of studies have compared the use of the multiple regression technique using semiempirical parameters such as tt and o-, and parameters calculated for the particular molecules from molecular orbital theory. Hermann, Culp, McMahon, and Marsh (23) studied the relationship between the maximum velocity of acetophenone substrates for a rabbit kidney reductase. These workers were interested in the reaction mechanism, and two types of quantum chemical calculations were made (1) extended Huckel treatment, and (2) complete neglect of differential overlap (CNDO/2). Hydride interaction energy and approaching transition-state energies were calculated from the CNDO/2 treatment. All these parameters plus ir and a values were then subjected to regression analysis. The best results are presented in Table II. 

Recently Spellmeyer and Houk [27] conducted a systematic study of the influence exerted by the size of basis sets and by correlation effects upon the activation energy of the reaction cyclobutene-butadiene. Parallel with the nonempirical calculations, this reaction was studied by means of the most frequent semiempirical methods MINDO/3, MINDO, and AMI (see below Sect. 2.3.2). The authors think, quite correctly, that the experimental value of the activation energy 32.9 0.5 kcal/mol should be compared with the results of only those empirical methods whose parameterization includes corrections for thermal vibrations and the energy of zero vibrations. At the same time, nonempirical calculations have to be compared with the value 34.5 kcal/mol, which is the result of the subtraction of the difference between the energies of zero vibrations and the energies of thermal vibrations of the ground and the transition states from the experimental value. Figure 2.4 shows some results from the work [27]. 

Molecular orbital calculations, whether by ab initio or semiempirical methods, can be used to obtain structures (bond distances and angles), energies (such as heats of formation), dipole moments, ionization energies, and other properties of molecules, ions, and radicals—not only of stable ones, but also of those so unstable that these properties cannot be obtained from experimental measurements." Many of these calculations have been performed on transition states (p. 279) this is the only way to get this information, since transition states are not, in general, directly observable. Of course, it is not possible to check data obtained for unstable molecules and transition states against any experimental values, so that the reliability of the various MO methods for these cases is always a question. However, our confidence in them does increase when (1) different MO methods give similar results, and (2) a particular MO method works well for cases that can be checked against experimental methods. ... 

Reaction of norbomadiene 74 (in excess) with 7V-benzyl aziridine 67 formed exclusively the all-sy l l-adduct 77. This stereochemistry, confirmed by NOE between Ha and Hb, resulted from attack at the underface of the dipole by the exo-face of the dipolarophile. Similarly, reaction of A -benzyl aziridine 67 with the diacetoxybenzonorbomadiene 30 gave a single adduct 78 (Scheme 11), the symmetrical structure of which was clearly apparent in the ll NMR spectrum. These stereochemical outcomes demonstrated that the transition state (TSa), in which the methano-bridge was adjacent to the (V-substituent, was favoured in the A -benzyl series (X and R small), and in accord with the semiempirical calculations. 

The calculations were performed at the semiempirical level using AMI parametrization. The results for the methyl chloride reaction (Table 8) supported Williams earlier findings for the methylammonium ion-ammonia reaction (p. 147) and the results by Wolfe and Kim in that the inverse secondary a-deuterium KIE arose from an increase in the C —H stretching force constants which accompanied the change from sp3 hybridization at the a-carbon in the reactant to the spMike hybridization in the transition state. More important, however, were the observations that (i) the total KIE is dominated by the vibrational (ZPE) component of the KIE with which it correlates linearly, and (ii) that the inverse contribution from the C —H(D) stretching vibrations is almost constant for all the reactions. Ibis suggests that the contribution from the other vibrations, i.e. the rest in Table 8, determines the magnitude of the KIE. In fact, Barnes and Williams stated that the... 

The mechanism of the dissociation of 1,2,3-trioxolanes to carbonyl oxides and carbonyl compounds has been studied by theoretical methods. Earlier ab initio calculations concluded that a biradical pathway and a concerted pathway were equally probable <81JA3619, 8UA3627), though it has been suggested that the transition state was not sufficiently characterized in these calculations to enable firm conclusions to be drawn from this work <91JA735>. More recent semiempirical AMI... 

Semiempirical AMI calculations on the transition state for the retroene-type elimination of propene from allylamines reveal that the most favoured geometry resembles a half-chair or a flattened boat.66 In keeping with experimental observations, it is predicted that electron-donor substituents on nitrogen should promote the reaction since the negative charge on this atom decreases in the polar transition state. 

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