Research On Regio-Selective C(sp~3)-H Bond Functionalization Directed By Nitrogen Radical

Nitrogen radical is an important reaction intermediate with high reaction activity,fast reaction speed,high regioselectivity,and relatively mild reaction conditions.The functionalization of nitrogen radical oriented long-range hydrocarbon bonds provides an effective way for the introduction of functional groups in organic molecules.In recent years,there have been endless reactions to realize the functionalization of carbon-carbon bonds and carbon-hydrogen bonds through the remote migration of functional groups involving nitrogen radicals,making the remote migration strategy of functional groups based on free radicals a research hotspot.This thesis focuses on the high reactivity of amide nitrogen radicals,and realizes regioselective hydrocarbon bond functionalization reaction through 1,5-hydrogen transfer(HAT),which can efficiently reconstruct the molecular structure.First of all,we have developed a copper catalyzed intramolecular distal C(sp~3)-H iminolactonization of carboxamides involving amidyl radical generation 1,5-HAT and cyclization.This transformation smoothly proceeds under mild conditions,with primary,secondary,and tertiary C(sp~3)-H bonds and provides a powerful protocol for synthesis of iminolactones.In addition,some control experiments were performed to gain insights into the iminolactonizaiton cyclization.Further investigations to broaden the synthetic application to other heterocycles are in progress.Secondly,we have carried out a preliminary study on the intermolecular cross dehydrogenation coupling reaction between the remote C(sp~3)-H bond and heterocyclic aromatic hydrocarbons in the amide catalyzed by copper.With Cu CN and 1,10-Phenanthroline as the catalyst system and potassium tert-butanol as the base,we can simultaneously realize the double activation of the remote C(sp~3)-H bond of N-fluoroamide and the C(sp~3)H bond of heterocyclic aromatic hydrocarbon,and complete the intermolecular dehydrogenation cross coupling reaction.At present,the further optimization of the reaction conditions,the investigation of substrate practicability and the mechanism verification experiment are under way.