Novel bridgehead bicyclic lactams: (a) Molecules predicted to have O-protonated and N-protonated tautomers of comparable stability; (b) hyperstable lactams and their O-protonated tautomers

The N- and O-protonated tautomers of 1-azabicyclo[3.3.1] nonan-2-one are predicted computationally to be comparable in stability. This was experimentally verified. The same theoretical models are employed to explore a wider range of bridgehead bicyclic lactams. Some additional examples are identified: some slightly preferring N-protonation and some O-protonation. Winkler-Dunitz parameters are employed to see if a pattern in geometry would emerge to help in the prediction of protonation preference. A number of larger bicyclic lactams are identified as possibly being hyperstable in O-protonation. (C) 2014 Elsevier Ltd. All rights reserved.