Study On The C-H Activation Of Pyridine N-Oxides And Their Functionalizations

Pyridine heterocycles are very important structural motifs of bioactivenatural products, pharmaceuticals and advanced functional materials. Furthermore,some of them are indispensable substances in life activities. Pyridine ring is verydifficult to activate owing to the electron withdrawing inductive effect of nitrogen thatdecrease the electron density of pyridine ring. When pyridine is oxidized to pyridineN-oxide, the activity of pyridine ring is increased significantly. Subsequently, variousefforts have been devoted to the functionalization of N-oxides, including arylation,alkynylation, alkenylation, alkylation, amination, amidation, acyloxylation, acylation,sulfonylation under transition-metal-catalyzed or transition-metal-free conditions.Moreover, the resulting products are reduced easily to generate the correspondingdeoxygenation product pyridines under mild conditions. Pyridine N-oxide regardingas a useful intermediate has the wide range of applications in organic synthesis. Thispaper is focused on study of the synthetic methods for constructing pyridineheterocycles under transiton-metal-catalyzed and transition-metal-free conditions, andit involved in the following two aspects:(1) An efficient oxidative-cyclization to straightforward synthesis ofbenzofuro[3,2-b]pyridine1-oxides with high region-selectivity via intramoleculardual C H activation in presence of Pd(PPh3)2Cl2as the catalyst, Ag2O as the oxidantwas developed. The resulting products could be deoxygenated easily by Pd/C to thecorresponding benzofuro[3,2-b]pyridines in excellent yields.(2) A novel and efficient method based on the cross-coupling reactions of pyridineN-oxides with ethers between C(sp2)–H/C(sp3)–H bonds in the presence of TBHP wasdeveloped. The resulting products could be reduced by Zn and NH4Cl to generate thecorresponding deoxygenation product pyridines under mild conditions. The reactionhas advantages with simple operation and environment-friendly.