When analyzing why reactions happen the way they do stereochemically, chemists are often quick to jump to common conformational (structural) motifs: six-membered chairs, staggered chains, etc. Invoking ubiquitous destabilizing effects is also common: allylic strain, eclipsing, bumping, etc. One thing to keep in mind, however, is that molecules in higher-energy states tend to be more reactive than those in their most stable states! If a molecule can access a local energy well that’s higher in energy than its global minimum and still proceed along some reaction path with comparable transition state energy, this translates into an overall lowering of the activation energy for the process involving the more reactive conformation, and renders it more favorable than the same transformation from the lowest-energy conformation of the molecule. In other words, molecules often exploit the fact that they can access higher-energy conformers in order to ease the burden of activation energy.
The endgame of all this physical organic mumbo-jumbo is that stereochemical analysis of organic reactions should take into account higher-energy reactive conformations, NOT ground-state conformers! Considering ground-state conformers doesn’t reflect reality for the molecule at the moment it actually wants to react.
That doesn’t mean considering ground states always leads to the wrong result, however. Cram’s rule, which explains diastereoselectivity in additions of nucleophiles to alpha-stereogenic carbonyls, stood for sixteen years as an empirical (but physically flawed) stereochemical principle. The conformation of the carbonyl compound he invoked was based on ground-state rather than “reactive” principles. Felkin and Anh improved on the Cram model by considering a different dihedral angle between the carbonyl group and the large group on the alpha stereocenter (ninety rather than zero degrees)–a conformation that is probably not the ground state, but one that leads to the lowest-energy transition state and the lowest overall activation energy for the addition process.
Stereoelectronic effects can also play an intriguing part in this phenomenon, especially when one considers how they can change with the conformation of a molecule. It’s always a good idea to keep in mind that the orbital manifolds of molecules are conformation dependent! Hyperconjugative effects vary with the dihedral angles between bonds and orbitals. Allylic alcohols provide an interesting case–although a dihedral between the alkene and the C-O bond of zero degrees may lead to substantial allylic strain, this conformation fixes the alkene HOMO at its highest energy and most reactive point! Any other angle between the C-O bond and the alkene leads to some delocalization of the alkene pi orbital into the C-O antibonding orbital.Here’s a case where considering the ground-state conformer could get you into trouble. The right-hand structure is somewhat ambiguous as to which face of the alkene would get attacked by an electrophile…I might go with the bottom face, considering the directly up-pointed OH group. But the left-hand, reactive conformer makes it clear that electrophilic attack would occur from the top face, away from the methyl group. I don’t have a reference, but I’m pretty sure this is the diastereoselectivity observed.