Study On The Radical Involved Direct C(sp~3)-H Bonds Functionalization

This thesis covers the direct constructions of C(sp~3)-N, C(sp~3)-O, C(sp~3)-C(sp2) bonds via radical involved C(sp~3)-H bonds functionalization of simple carbon hydrides, including alkyl ethers, benzylic and allylic compounds, and also domanstated the application of this concepts to the novel approach of the hemiaminal ether skeletons, the synthesis of alkly oxime amines and the late-staged functionalization of coumarins.1. Traditional approaches toward the construction of the hemiaminal frameworks include the cascade reactions, hydroamination, substitution, the transition-metal carbene insertion and so on. Here, we developed a radical involved amination of the alkyl ethers, in which the combination of n-Bu4NI/t-BuOOH was used as a powerful oxidant by the genereation of the hypervalent reagent in situ. A variety of amines and alkyl ethers could undergo the radical invovled C(sp~3)-H bond amination to afford a series of hemiaminal ether skeletons.2. Based on this work, we developed a metal-free approach towards the radical cross-coupling reaction. It is challenging to achieve the selective bond formation between two active radicals due to the high reactivities of them. Thus the cross-coupling reaction between two active radicals often needs the participation of the transition-metal as the catalyst or even as the oxidant to stalize the active intermediates. On the other hand, PINO is widely used as a catalyst in the radical invovled reactions in both the laboratory and the industry. Here, we use the combination of n-Bu4NI/t-BuOOH to achieve the metal-free approach of the synthesis of alkyl oxime amines via the cross-coupling reactions between benzylic/allylic compounds and PINO generated in situ from NHPI, which might gain a new light in the radical invovled cross-coupling reactions.3. We also demonstrated the possibility of the late-staged functionalization of coumarins via the direct C(sp~3)-H bonds activation. This transformation was successfully accomplished under basic conditions catalyzed by Cobalt. A series of the analogs were synthized through this method.