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 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 the key to explaining 4 and 5 's diverging reactivity.