Backside versus Frontside S2 Reactions of Alkyl Triflates and Alcohols.

Nucleophilic substitution reactions are elementary reactions in organic chemistry that are used in many synthetic routes. By quantum chemical methods, we have investigated the intrinsic competition between the backside S2 (S2-b) and frontside S2 (S2-f) pathways using a set of simple alkyl triflates as the electrophile in combination with a systematic series of phenols and partially fluorinated ethanol nucleophiles. It is revealed how and why the well-established mechanistic preference for the S2-b pathway slowly erodes and can even be overruled by the unusual S2-f substitution mechanism going from strong to weak alcohol nucleophiles.