Conformational Landscape of -Halopropiophenones Determined by ⁿJ_C-H NMR Reveals Unexpected Patterns and Geometric Constraints

The conformational features of alpha-halopropiophenones were investigated to understand the influence of alpha-halogens on conformation through hyperconjugative interactions, electrostatics, and steric factors. Using NMR, C-H scalar coupling constants were measured in different solvents, revealing a pattern in the conformational equilibria, which we validated by computational means. This behavior arises largely from hyperconjugative effects with the exception of the fluoro-derivatives, which are also influenced by steric and electrostatic interactions. In all cases, the contribution to hyperconjugation of the alpha-halo ketones is driven by the oxygen lone pair (rather than the C-X bond), which donates electron density to the adjacent C-C bonds. Additionally, C-C alpha bond rotation generates distortions in the side chain, responsible for destabilization, thus affecting system conjugation. These structural features identified for the alpha-halo ketones are also reflected in their reactivity, which is distinct from that expected for nucleophilic addition.