Accelerating Effect of Triazolyl and Related Heteroaryl Substituents on S_NAr Reactions: Evidence of Hydrogen-Bond Stabilized Transition States

摘要

The remarkable accelerating effect of 1,2,3-triazolyl substituents on S_NAi reactions has been investigated through systematic experiments and density functional theory calculations. The lone pair electrons of an ortho-triazolo substituent play a key role in lowering the activation energy for nudeophilic addition via formation of a preferential hydrogen bond with the amine nudeophile at the transition state for addition. In an extension of this finding, a series of related heteroaryl groups with similar electron pair donor properties have also been found to facilitate S_NAr reactions. The experimentally determined solvent effect provides further support for this rationale, which was utilized to achieve an ortho-selective substitution on a difluoroarene substrate.