Studies On Copper,Nickel And Palladium Catalyzed C-N Bond Coupling Reactions

Transition-metal catalyzed cross-coupling reaction to form C-N bonds has emerged as an extremely general technology for the preparation of nitrogen-containing compounds in numerous areas of basic and applied research.Owing to the widespread presence of nitrogenous compounds in pharmaceuticals,natural products,organic materials,and catalysts,the application of this process has been exceptionally broad.Accordingly,we turned our attention to develop a convenient and effective method to constuct a diversity of nitrogenous compounds.First,a method for the one-pot synthesis of substituted amides from aldehydes and amides is presented.Namely,condensation of aldehydes with N-tosylhydrazide generated the N-tosylhydrazones which were then reductively cross-coupled in situ with primary or secondary amides in the presence of a copper catalyst to afford secondary or tertiary amides.Amides obtained in 33%-99%yield.TBAI was added to increase the solubility of intermediate in organic solvent.By now,the method provides a straightforward route for the synthesis of substituted amides from readily available aldehydes via a transition metal catalyzed C(sp3)-N amide bond forming reaction has not been reported.Second,a Cul-catalyzed reductive coupling of ketone-derived N-tosylhydrazones with amides is presented.Under the optimized conditions,an array of N-tosylhydrazones derived from aryl-alkyl and diaryl ketones could couple effectively with a wide variety of(hetero)aryl as well as aliphatic amides to afford the N-alkylated secondary or tertiary amides in 14%-98%yield.The method suggests different functional groups on the aromatic ring were tolerant,such as halogen.The results demonstrate that the reaction was well selective.Third,investigating the Ni(?)-mediated ortho-amination of C(sp2)-H bond directed by(quinolin-8-yl)amine(AQ-amine).The reaction used NiCl2 as catalyst,(quinolin-8-yl)amine as directing group,azides as amino sources to construct the C-N bond by C(sp2)-H activation and obtained in 41%-80%yield.Then,we investgated the mechanism through control experiments,which proved the C-H bond cleavage is the rate-determining step.The structure of 2-(4-methylphenylsulfonamido)-N-(quinolin-8-yl)benzamide was proved by single crystal X-ray diffraction experiment.At last,studying the Pd-catalyzed ortho C-H amidation of diarylphosphinamides with morpholine derivatives and optimized the conditions of catalysts,oxidants,addtives and ligands in the presence of acid or basic circumstances.The reaction achieved in the pesence of Ag2CO3,Ac2O and duroquinone in 45%yield.The product was examined by nuclear magnetic resonance and single crystal X-ray diffraction.Additionally,byproducts were also separated and characterized.This work was rough and needed further investigations,but the method represented the first example of C-H amidation of diarylphosphinamides.