Copper-catalyzed Oxidative Coupling Of Quinazoline 3-oxides With C-H Bond

Oxidative coupling of two C–H bonds for the construction of C–X(X= C,O,N,S,P etc)bond has emerged as an attractive and ideal tool for organic chemists because prior functionalization is not necessary,thus making the oxidative coupling strategy environmentally friendly,atom-and step-economic,and sustainable.Quinazoline represents one of the privileged scaffolds of pharmaceutical agents and natural products with interesting biological activities.As a consequence,considerable efforts have been made for the synthesis and direct functionalization of quinazoline derivatives.However,it is still far from being developed due to the low efficiency and poor regioselectivity of the current available methods.We have developed copper-catalyzed oxidative coupling of quinazoline 3-oxides with C(sp~2)–H and C(sp~3)–H.Owing to the mild reaction conditions,easy handling and versatility of the substrate,this method should find broad application in the context of building quinazoline libraries for drug discovery and material science.This thesis focuses on the following two parts:(1)We developed the first copper-catalyzed oxidative coupling of heteroarenes with unactivated aldehydes,which act as acyl donors in this reaction.This method not only offered a straightforward approach to quinazoline based diaryl ketones but also provided an unexpected synthetic strategy for the cyclic hydroxamic esters derived from quinazolines.Owing to the mild reaction conditions,easy handling and versatility of the substrate,this method should find broad application in the context of building quinazoline libraries for drug discovery and material science.(2)We further studied the copper-catalyzed oxidative coupling reactions of quinazoline N-oxides and methylarenes.This is the first method using quinazoline Noxides to build quinazolinone skeleton with C(sp~3)–H under mild reaction conditions.This method not only realized C(sp~3)–H functionalization and C-O formation,but also realized benzylation of the 3 position of quinazoline.We have also completed an attempt from C(sp~2)–H to C(sp~3)–H,which was further proved that quinazoline 3-oxides can be used as the precursor of Quinazoline-4-one-3-oxygen radical.It can be used to provide new ideas and strategies for the synthesis of quinazoline.