Synthesis Of Pyridine Compounds Based On Tandem Reactions

Pyridine derivatives are an important class of azaheterocycle found in many natural products and biologically active molecules.Meanwhile,the pyridine compounds play a central role in diverse range of natural product chemistry and synthetic pharmaceutical chemistry.Owing to the significances of pyridines in organic synthesis,the pyridine compounds entice a wide range of interest to organic chemists.In this thesis,the starting point of the work is developing the novel,simple,effecient and green routes to synthesize pyridine compounds.A practical protocol is developed by using carbon dioxide as a promoter for the C=N bond cleavage of amidines.Secondly,the direct synthesis of pyridine compounds from?,?-unsaturated oximes by copper catalysts was realized.The details are as followings:1.Direct constructing of multi-substituted pyridines with amidines and 1,3-diynes via CO₂-promoted C=N bond cleavageDespite of numerous recent advances in this area,the utility of amidines as the nitrogen source were not realized in the construction of pyridines.We introduced diynes as a reaction partner with DBU and several other amidines to achieve a cross-cyclization using CO₂ as the promoter for the construction of muti-substituted pyridines.A novel and atom-economic protocol is developed using carbon dioxide as a promoter for the C=N bond cleavage of amidines.CO₂ played a decisive role in the cleavage of C=N bond owing to the activation of C=N bond of DBU by atomspheric CO₂.The mechanistic isotope labeling experiments suggested that the oxygen atom of resulting carbonyl group was originated from water.This C=N bond cleavage promoted by CO₂ could potentially open up new perspectives in the utilization of C=N type nitrogen source in synthetic chemistry.2.Direct synthesis of multi-substituted pyridines from?,?-unsaturated oximes by Cu/NaHSO₃We developed a facile method to synthesize muti-substituted pyridine compounds by using simple copper catalysts catalyzed oximes.In this chapter,?,?-unsaturated oximes not only generated a nucleophilic copper?II?enamide with the aid of copper catalyst but also played a key role to afford the acceptor of Michael addition.We reasoned that the combination of a nucleophilic copper?II?enamide and?,?-unsaturated oximes under the mild condition could furnish the cross cyclization in a regio-and chemo-selective fashion.Through the oxidation of copper?II?,the desired pyridine was released by thearomatization.The accessible starting materials,combined with the mild reaction conditions and a selective yielding manner,conspire to make this appealing method for the rapid synthesis of substituted pyridine structures.