Concerted nucleophilic aromatic substitutions.

ABSTRACT: Nucleophilic aromatic substitution (S_NAr) is one of the most widely applied reaction classes in pharmaceutical and chemical research, providing a broadly useful platform for the modification of aromatic ring scaffolds. The generally accepted mechanism for S_NAr reactions involves a two-step addition-elimination sequence via a discrete, non-aromatic Meisenheimer complex. Here we use ¹²C/¹³C kinetic isotope effect (KIE) studies and computational analyses to provide evidence that prototypical S_NAr reactions in fact proceed through concerted mechanisms. The KIE measurements were made possible by a new technique that leverages the high sensitivity of ¹⁹F as an NMR nucleus to quantitate the degree of isotopic fractionation. This se

SUBMITTER: Kwan EE 

PROVIDER: S-EPMC6105541 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature