Mechanistic studies of the cleavage and transformation of unactivated C_(sp3)-H bonds are a significant field of chemistry.Overcoming the inherent low acidity of C-H bonds to activate the inert substrates is challenge...Mechanistic studies of the cleavage and transformation of unactivated C_(sp3)-H bonds are a significant field of chemistry.Overcoming the inherent low acidity of C-H bonds to activate the inert substrates is challenge under mild conditions.And their complex multi-step transformations may also hinder mechanistic understanding.Herein,we perform theoretical calculations and experimental studies to explore the C_(sp3)-H bonds activation and acylation mechanisms of toluene/thioether using the relatively weak base LDA.A synergistic"main and auxiliary"model was revealed involving dual lithium metal by LDA dimers,and the aryl dilithium species as an intermediate base can facilitate C_(sp3)-H activation.This model not only aids in understanding the acidity of unactivated C_(sp3)-H bonds and the nucleophilicity of their conjugate bases for their kinetic control through cooperative interactions,but also predicts unusual kinetic isotope effects(KIE)for newly designed 2-(methylthio)naphthalene that are experimentally validated.This research is expected to provide a crucial scenario for the cleavage and transformation of unactivated C_(sp3)-H bonds and the development of new functionalities for alkali metal reagents.展开更多
基金the National Key Research and Development Program of China(No.2021YFA1500100)the National Natural Science Foundation of China(Nos.92156017 and 21890722)+1 种基金“Frontiers Science Center for New Organic Matter”,Nankai University(No.63181206)Haihe Laboratory of Sustainable Chemical Transformation of Tianjin(No.24HHWCSS00019)for generous financial support。
文摘Mechanistic studies of the cleavage and transformation of unactivated C_(sp3)-H bonds are a significant field of chemistry.Overcoming the inherent low acidity of C-H bonds to activate the inert substrates is challenge under mild conditions.And their complex multi-step transformations may also hinder mechanistic understanding.Herein,we perform theoretical calculations and experimental studies to explore the C_(sp3)-H bonds activation and acylation mechanisms of toluene/thioether using the relatively weak base LDA.A synergistic"main and auxiliary"model was revealed involving dual lithium metal by LDA dimers,and the aryl dilithium species as an intermediate base can facilitate C_(sp3)-H activation.This model not only aids in understanding the acidity of unactivated C_(sp3)-H bonds and the nucleophilicity of their conjugate bases for their kinetic control through cooperative interactions,but also predicts unusual kinetic isotope effects(KIE)for newly designed 2-(methylthio)naphthalene that are experimentally validated.This research is expected to provide a crucial scenario for the cleavage and transformation of unactivated C_(sp3)-H bonds and the development of new functionalities for alkali metal reagents.
