Small and medium-sized bridgehead bicyclic lactams: A systematic ab initio molecular orbital study

Optimized ab initio molecular orbital calculations on nine bridgehead bicyclic lactams ranging from the 2.2.2 to the 4.3.3 series indicate variations in structural properties, resonance energies, proton affinities, and core orbital ionization energies that reflect the trans-cycloalkene analogy. The smaller lactams are calculated to be N-protonated, the larger O-protonated, and the ''crossover'' is predicted to occur around the 3.3.1 system. On the basis of resonance energies, larger bridgehead bicyclic lactams could be considered to be hyperstable as Schleyer and co-workers define the concept for larger bridgehead alkenes. This, hyperstability should be apparent in the kinetics of the nucleophilic substitution reactions of the lactams, such as hydrolysis, but not in the thermochemistry of these reactions.