The Role of Through-Bond Stereoelectronic Effects in the Reactivity of 3-Azabicyclo[3.3.1]nonanes
Hyperconjugation/conjugation through-bond stereoelectronic effects were studied with density functional theory (DFT) in the context of 3-azabicyclo[3.3.1]nonanes to unravel puzzling differences in reactivity between a vinylogous chloride (4) and a vinylogous ester (5). These compounds—whose structures differ only by one substituent—were found to display strikingly different reactivities in hydrochloric acid by Risch and co-workers (J. Am. Chem. Soc. 1991, 113, 9411–9412). Computational analyses of substituent effects, noncovalent interactions, natural bond orbitals, isodesmic reactions, and hydration propensities lead to a model for which the role of remote, through-bond stereoelectronic effects is key to explaining 4 and 5’s diverging reactivity.
