Driving -butyl axial: the surprising cyclopropyl effect.

The presence of a small spirocyclic ring at an adjacent position alters the conformational preference for equatorial substitution in six-membered rings. DFT calculations and low-temperature H NMR experiments demonstrate that alkyl groups larger than methyl possess negative A-values when geminal to a spirocyclopropane, with larger groups such as isopropyl and -butyl being exclusively axial at -78 °C. Similar effects are found for heteroatoms, including halogens, and for a range of other electron-withdrawing substituents.