Synthesis Of Pyrrole Derivatives Based On The Strategy Of C-H Bond Activation Relay

The C-H bond activation is known as the "Holy Grail" of organic chemistry,and has been one of the hottest research topics in organic synthesis.In the past decades,the remote C-H bond activation was focused by more and more chemists,and the remote C-H activation induced by free radicals has been widely studied.The radical induced remote C-H bond activation is mainly mediated by the intramolecular hydrogen atom transfer(HAT),whose driving force is the BDE difference between the starting materials and products.Generally,HAT process is initiated by a nitrogen centered or oxygen centered radical.The generation of these heteroatom centered radicals usually requires harsh reaction conditions or prepreparation of functionalized substrates.The example of remote C-H activation induced by a carbon centered radical remains rare,due to the small BDE difference between the starting materials and products.Therefore,a strategy of C-H bond activation relay(CHAR)was proposed:The carbon centered radical is generated under mild conditions,followed by coupling with oxygen to produce a peroxide radical intermediate.Then,the peroxide radical induces the intramolecular HAT and abstracts a hydrogen atom at the appropriate site,providing a target radical.After the subsequent reactions,the functionalized product is afforded,thus achieving the remote C-H bond activation.In this thesis,a series of pyrrole derivatives are efficiently synthesized based on the strategy of C-H bond activation relay,providing a new way to the remote C-H bond activation mediated by free radical intermediates and realizing the efficient synthesis and functionalization of pyrroles.1.Using the counter ion of TBPA as the chlorine atom donor,a remote C-H bond activation of proline esters was successfully achieved,in which a C-H activation relay(CHAR)process is the key step to fulfill the direct functionalization of sp3 C-H bond.Based on this reaction,a series of chlorinated pyrrole derivatives were synthesized in high yields.It provides a new way to promote the participation of counter-ions in organic reactions.This reaction is superior in mild reaction conditions,broad substrate scope and good functional group tolerance Furthermore,this reaction can be scaled up to the gram scale,which might be extended to large-scale synthesis of pyrroles.2.Based on the above results(the strategy of CHAR),a dehydrogenation aromatization of proline esters and remote C-H bond bromination was smoothly achieved,using copper bromide both as an oxidant and bromine atom donor,giving a series of 4-bromopyrrole derivatives in good yields with high regioselectivity.This reaction opens up a new approach to facilitate the radical remote C-H bond activation.3.Using TBPA/O2 as the initiator,the C-H bond chlorination of pyrroles,indoles and electron-rich aromatics was efficiently realized in the presence of Cu(OAc)2.This reaction reveals that TBPA can be employed as a new chlorination reagent to participate in various CH bond chlorination of heteroarenes.