Steric Effects Dynamic Stereochemistry

Nonbonding interactions play a major role in determining the three-dimensional structure of a molecule. Such interactions are composed of repulsive and attractive contributions, such as van der Waals repulsion, London dispersion forces, coulombic interactions, and delocalizations of electrons due to the through-space interactions between atomic orbitals. 

When conjugation is possible between the heterocyclic ring and the substituent, preference for maintaining a planar arrangement for maximum conjugation is balanced against the nonbonded interactions. 

intramolecular steric effects are of primary importance in determining the conformation of alkyl and aryl substituents attached to heterocyclic frameworks. The dynamic processes associated with these conformational states are also strongly dependent on the steric modifications between ground state and transition state. It can thus be inferred that a quantitative approach of steric effects can be obtained through these data. 

The structure of a molecule may be studied in the gas phase, in solution or liquid state, or in the solid or crystalline state, and different techniques are applied. Furthermore, the various methods give different and sometimes complementary information on structure, conformation, and dynamics. 

Microwave spectra (74PMH(6)5) provide a rich source of detailed molecular structures in the gas phase. For molecules with more than four atoms the isotopic replacement technique must be used in order to obtain a complete structure. Not only the ground-state conformation but also rotational barriers 

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Understanding, rationalizing, and predicting both reactivity and the energetics of dynamic stereochemistry are of major importance in heterocyclic chemistry and one or both of these topics are a concern of the majority of the contributions in Advances in Heterocyclic Chemistry. No previous systematic study has been reported which treats quantitatively steric effects in heteroaromatics this is the purpose of this article. 

Our article will be mostly concerned with the importance of steric effects in rationalizing the reactivity and dynamic stereochemistry of heteroaromatics and with recent attempts to bridge the gap between them these topics correspond to three major sections of the chapter. 

There has been a decisive evolution in the treatment of steric effects in heteroaromatic chemistry. The quantitative estimation of the role of steric strain in reactivity was first made mostly with the help of linear free energy relationships. This method remains easy and helpful, but the basic observation is that the description of a substituent by only one parameter, whatever its empirical or geometrical origin, will describe the total bulk of the substituent and not its conformationally dependent shape. A better knowledge of static and dynamic stereochemistry has helped greatly in understanding not only intramolecular but also intermolecular steric effects associated with rates and equilibria. Quantum and molecular mechanics calculations will certainly be used in the future to a greater extent. 

Stability and reactivity of crown-ether complexes, 17, 279 Stereochemistry, static and dynamic, of alkyl and analogous groups, 25, 1 Stereoelectronic control, the principle of least nuclear motion and the theory of, 24, 113 Stereoselection in elementary steps of organic reactions, 6, 185 Steric isotope effects, experiments on the nature of, 10, 1... 

Vogtle, F., and Hohner, G. Stereochemistry of Multibridged, Multilayered, and Multistepped Aromatic Compounds. Transanular Steric and Electronic Effects. 74, 1-29 (1978). Vogtle, F., and Neumann, P. 12.2) Paracyclophanes, Structure and Dynamics. 48, 67-129 (1974). 

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