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 compoundswhose structures differ only by one substituentwere
found to display strikingly different reactivities in hydrochloric
acid by Risch and co-workers (J. Am. Chem. Soc.199111394119412). 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.