The Synthesis Of C2-modified Pyridines And Quinolines Via The C(sp~3)-H Bonds Functionalization

C2-modified pyridine and quinoline derivatives are very important organic molecules which could befound in many physiologically active alkaloids and important structural unit having antiviral, antibacterialand anticancer activity of the drug. Therefore their synthesis play an important role in medicinal chemistry.The synthesis of C2-modified pyridine and quinoline derivatives via the direct C-H bond activation havethe following advantages, such as simple, efficient and high product yields.According to the literature search, the reactions of the C(sp3)-H bond functionalization of2-alkylpyridines and2-alkyl quinolines are divided into the following four categories:1), the reactions ofintroducing activating groups on2-alkyl pyridines.2), the reactions of unactivated2-alkyl pyridines and2-alkyl quinolines with aryl halides.3), the addition reactions of unactivated2-alkyl azaarenes withcompounds containing a double or triple bond.4), the asymmetric reactions catalyzed by metal chiralligand for unactivated2-alkyl azaarenes. The addition of2-alkylpyridines and quinolines to compoundscontaining C=O are few reported. In view of this, we design two reaction pathways for the addition of2-alkylpyridines or quinolines to C=O double bond compounds which provide new methods for theefficient synthesis of C2-modified pyridine and quinoline derivatives.In this paper, we have developed an efficient copper-catalysed addition of2-alkyl azaarenes to ethylglyoxylate through C(sp3)–H bond functionalisation. Using this approach, we synthesized21examples ofquinoline and pyridine derivatives that rapid lengthened of the2-position carbon chain. Moreover, we havedeveloped an efficient Br nsted acid catalyzed reaction of2-methyl azaarenes and aromatic aldehydes togive1,3-di(2-quinolyl)propane derivatives through tandem C(sp3)-H bond activation. This protocolprovides a simple and rapid approach to access a variety of1,3-di(2-quinolyl)propane derivatives, whichgetting28examples of new compounds.This paper opens up new avenues for the synthesis of C2-modified pyridines and quinolines, which issimple and easy operation. By observing experiments, analysis of experimental results and referring to therelevant literature, we also briefly discussed and elaborated on the mechanism.The target products were confirmed by1H NMR,13C NMR, and HRMS.discussed and elaborated onthe mechanism.