The Synthesis And Application Of Pyridiyne Precursors

Polyfunctionalized pyridine ring structure exists widely in natural products and drug molecules.To find ways to efficiently build multi-substituted pyridine framework is one of the research goals in synthetic chemistry.Pyridynes are a kind of active intermediates due to its unique structure,which can conveniently form two new contiguous chemical bonds.Hence,it's of great advantage to use pyridine to build multi-substituted pyridine structure.In recent years,there are more and more reports about using 2,3-pyridyne or 3,4-pyridyne as intermediates to get polyfunctionalized pyridine.However,with these methods,they can only achieve disubstitution in the vicinal positions of a pyridine ring.Only if with further transformation,we can get multiple substituted product,which limits the application of pyridyne in organic synthesis.This project is inspired by the previous work accomplished in our lab,especially the novel domino aryne precursor TPBT,which can achieve the trifunctionalization of benzene through tandem nucleophilic processes.Thus,we proposed a new proposal of pyridiyne.It shares the analogous structure like TPBT,and could be expected to generate pyridyne twice in a tandem process.Consequently,we can achieve tri-substituted pyridine within one step.Based on this,we synthesized 2,3-pyridiyne precursor and 3,4-pyridiyne precursor,the later of which can generate pyridiyne in the presence of fluoride ion successfully,reacting with furan,sulfonamide,thiobenzamide.Though the yield is not good enough,it provides a new method to form pyridine multi-functionalization.Besides,during the research about 3,4-pyridine,we find out that it's lack of regioselectivity during nucleophilic reactions.Therefore,we tried to use Lewis acid to react with the pyridyne intermediate to change the electron distribution of the pyridine ring.After some attempts,we failed to reach the goal,but the relevant research is still on.