Nitrogen electron pair orientation

The preferred TS is a chair with the enolate oriented syn to the bulky pyrrolidine substituent. It was suggested that the syn acylation occurs through an envelope conformation of the pyrrolidine ring with the nitrogen electron pair oriented axially. 

This last study is quite interesting because it permits an evaluation of the anomeric effect for the nitrogen atom. Conformer 91 with the axial N-methyl group should be less stable than conformer 92 by approximately 1.3 kcal/mol on the basis of steric effects (one gauche form of n-butane, =0.9 kcal/mol and one gauche form of CHj — N - CHj-0, =0.4 kcal/mol). The second anomeric effect caused by the equatorial orientation of the nitrogen electron pair in 91 must compensate for the steric effect. An approximate value of 1.3 kcal/mol must therefore be taken for that electronic effect, a value close to that estimated for the oxygen atom of the acetal function. 

Vasella has suggested that the observed stereoselectivity is due to a stereoelectronic effect which strongly influences the stereochemistry of the transition state of the cycloaddition reaction. This stereoelectronic effect is caused by the nitrogen electron pair which is oriented antiperiplanar to the C-O bond of the... 

These interactions are most commonly observed for divalent chalcogen atoms and the nitrogen atom (the electron donor D) lies within the X-E-Y (E = S, Se, Te) plane, preferably along the extension of one of the covalent bonds as in 15.3. This anisotropy is a clear indication that these short E N contacts have some bonding character, i.e., they are subject to the geometric restrictions of orbital overlap. Eor example, in the diselenide 15.4 the nitrogen lone pairs are clearly oriented towards the Se-Se linkage. ... 

The steric number identifies how many groups of electrons must be widely separated in three-dimensional space. In ammonia, for example, the nitrogen atom bonds to three hydrogen atoms, and it has one lone pair of electrons. How are the three hydrogen atoms and the lone pair oriented in space Just as in methane, the four groups of electrons are positioned as far apart as possible, thus minimizing electron-electron repulsion. 

In comparison with the decomposition of taws-azoalkanes 20 a much larger group size effect has been found for the thermolysis rates of a few c/s-azoalkanes 24. Due to the repulsion of the free electron pairs on the two nitrogen atoms and due to steric interaction between the cis oriented alkyl groups cis azoalkanes 24 decom-... 

In piperidine the electron lone-pair can occupy either an axial or an equatorial position in 1-methylpiperidine the axial orientation (lb) is favoured by 99 1 over the equatorial (la). PE spectra and ab initio calculations on methylpiperidines indicate that axial 2-methyl substituents lower the amine lone-pair ionization potential by about 0.26 eV, while equatorial 2-methyl substituents as well as methyl groups on carbon atoms 3 and 4 lower the lone-pair IP by less than 0.1 eV63. This establishes the mechanism of stabilization of the amine radical cation as hyperconjugative electron release, which is larger for CC bonds than for CH bonds. The anti-periplanar orientation of the nitrogen lone-pair and the vicinal C—Me bond (lc) is much more favourable for this type of interaction than the synclinal orientation (Id). 

It was pointed out in Section III-D that free electron pairs at heteroatoms may be involved in the transmission mechanism of y.-SCSs. This participation can be probed effectively using conformationally rigid molecules with built-in heteroatoms in which the stereochemical orientation of the lone pair can be varied. Nitrogen is very suitable for this purpose, so most of the pertinent work has been done with piperidines and related bicyclic analogs. 

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