solvent, causing the equatorial position to be preferred. When X=NH2, again, no anomeric effect was observed and the equatorial position was always preferred. Overcoming the anomeric effect While the anomeric effect can cause stabilization of molecules, it does have a magnitude to its stabilization, and this value can be overcome by other, more destabilizing effects in some cases. In the example of spiroketals, the orientation on the upper left shows stabilization by the hyperconjugative anomeric effect twice, thus greatly stabilizing the orientation of the molecule. The orientation on the upper right only shows this hyperconjugative anomeric stabilization once, causing it to be the lesser preferred structure. However, when substituent are added onto the spiroketal backbone, the more preferred structure can be changed. When a large substituent is added to the spiroketal backbone, as seen in the lower left, the strain from having this large substituent, R, in the axial position is greatly destabilizing to the molecule. In the molecule on the lower right, R is now in the equatorial position, which no longer causes destabilization on the molecule. Therefore, without substituents, the upper equilibrium reaction is favored on the left hand side, while the lower equilibrium is favored on the right hand side, simply from the addition of a large, destabilizing substituent. Exo anomeric effect An extension of the anomeric effect, the exo anomeric effect is the preference of substituents coming off a ring to adopt the gauche conformation, while sterics would suggest an antiperiplanar conformation would be preferred. An example of this is 2-methoxytetrahydropyran. As the anomeric effect predicts, the methoxy substituent shows an increased preference for the axial conformation. However, there is actually more than one possible axial conformation due to rotation about the C-O bond between the methoxy substituent and the ring. When one applies the principles of the reverse anomeric effect, it can be predicted that the gauche conformer is preferred, suggesting the top left conformation is best in the figure above. This prediction is supported by experimental evidence. Furthermore, this preference for the gauche position is still seen in the equatorial conformation. Reverse anomeric effect This term refers to the apparent preference of positively charged nitrogen substituents for the equatorial conformation beyond what normal steric interactions would predict in rings containing an electronegative atom, such as oxygen. Substituents containing carbons with partial positive charges are not seen to exhibit the same effect. Theoretical explanations for