Quantum chemical study of the equatorial/axial exchange of different substituents in nitrogen and phosphorous-containing 6-membered rings: Role of charge transfer interactions

摘要

Understanding the nature of equatorial/axial conversion in six-membered rings is important because of involvement of these motifs in some biological systems. In this work we have studied the equatorial/axial exchange of nitrogen and phosphorous bearing six-membered rings with different representative substituents by using quantum chemistry methods. Three possible routes, i.e. heteroatom inversion and two ring flipping modes were considered. The feasibility of equatorial/axial conversion (based on ΔE~#) for the substituted piperidine rings with substituents was in the following order; H>CH_3 >Cl~OH~F， whereas for the phosphorous bearing six-membered rings it was H~F>OH>Cl~CH_3. In the piperidine system hydrogen and methyl substituents preferred the atom inversion route while the other substituents (Cl, F, OH) favored C4 site ring flipping in equatorial/axial conversion. For the phosphorous bearing rings, however, phosphorous retards the atom inversion mechanism and heteroatom site ring flipping is the preferred route for all substituents. We demonstrate that charge transfer effect is one of the key factors that determines the favored route in the presence of various substituents. We show how wave function analysis by natural bond orbital (NBO) method can be used as a straightforward technique to explain the most favored route in the equatorial/axial conversion of substituted 6-membered rings.