SN2 versus SN2′ Competition

We have quantum chemically explored the competition between the S(N)2 and S(N)2' pathways for X- + H2C=CHCH2Y (X, Y = F, Cl, Br, I) using a combined relativistic density functional theory and coupled-cluster theory approach. Bimolecular nucleophilic substitution reactions at allylic systems, i.e., C-gamma=C-beta-C-alpha-Y, bearing a leaving-group at the alpha-position, proceed either via a direct attack at the alpha-carbon (S(N)2) or via an attack at the gamma-carbon, involving a concerted allylic rearrangement (S(N)2'), in both cases leading to the expulsion of the leaving-group. Herein, we provide a physically sound model to rationalize under which circumstances a nucleophile will follow either the aliphatic S(N)2 or allylic S(N)2' pathway. Our activation strain analyses expose the underlying physical factors that steer the S(N)2/S(N)2' competition and, again, demonstrate that the concepts of a reaction's "characteristic distortivity" and "transition state acidity" provide explanations and design tools for understanding and predicting reactivity trends in organic synthesis.