Negative A-Values in Cyclohexanes: Reversal of the Preference for the Equatorial Conformation

This graphical review provides an overview of known exceptions to the general equatorial preference in 6-membered rings. As conformational analysis is critical to catalyst, reaction and drug design in conformationally flexible systems, understanding exceptions is paramount. Key exceptions to the equatorial preference discussed herein include various forms of the anomeric effect, electrostatic effects like classical and non-classical hydrogen bonding, hyperconjugation mediated effects, and strong equatorial gauche interactions including the effect of small spirocycles.