Driving t-Butyl Axial: The Effect of Small Spirocyclic Rings on A-Values

The presence of a small spirocyclic ring at an adjacent position alters the conformational preference for equatorial substitution in cyclohexane and piperidine rings. DFT and low-temperature 1H NMR experiments demonstrate that alkyl groups larger than methyl possess negative A-values when geminal to a spirocyclohexane. Similar observations are made for halogen and other electron withdrawing substituents. For small groups such as methyl and hydroxy, the A-value is near zero, while for groups such as amino, acetamido and aryl, the A-values are positive, but significantly smaller than for simple cyclohexanes. Similar effects are observed for other strained rings (epoxide, cyclobutane, ox-etane) and the concepts extend to acyclic models. The origin of the effect is traced to an increase in torsional strain in combination with hyperconjugative effects in the case of electron poor groups.