Research On Palladium-catalyzed Oxidative Transformations Involving Alkenes And Amines Under Molecular Oxygen

Transition-metal-catalyzed transformations have been found extensive applications inSynthetic Organic Chemistry. Especially, palladium-catalyzed reactions generally featureddiversity in chemical bond formation, excellent chemo-, regio-, stereoselectivities, as well asgreat tolerance of functional groups. Therefore, it constitutes an efficient strategy tosynthesize multifunctional compounds. The catalytic activity and selectivity of palladiumcatalysts could be modulated by changing the reaction conditions, such as the ligand, solvent,temperature, and additive.Oxidative reactions have been an important part of organic chemistry, and high selectivityand mild conditions of these processes become the current goals in modern synthetic organicchemistry. A number of oxidants have been employed in palladium catalytic systems, such asCu2+, BQ, DDQ, PhI(OAc)2, K2S2O8, which are not only expensive but also usually produceenvironmentally harmful byproducts. There is no doubt that molecular oxygen is an abundant,inexpensive, and environmentally friendly ideal oxidant with high atom economy, andharmless H2O was released after the reaction.In recent years, palladium-catalyzed reactions under molecular oxygen have attracted muchattention of chemistry researchers worldwide. These transformations generally could reducecosts, simplify products’ separation processes, enhance the atom economy, and improve theselectivities in most cases. The Pd(II)/O2catalytic systems have been employed in a widerange of laboratory and industrial research field. In our research, palladium-catalyzedreactions under molecular oxygen involving the oxidation of simple alkene substrates havebeen systematically studied based on the principle of “green chemistry”, and a variety ofnitrogen-containing organic molecules have been efficiently constructed. These novelstrategies would have broad application prospects in fields of the total synthesis of naturalproducts, pharmaceuticals, pesticides, as well as functional materials. The details aresummarized as follows:(1) Palladium-catalyzed selective oxidative cyclization based on the sequential formationof Csp2─Csp2bonds under molecular oxygen for the construction of a series of2-substitutedand2,3-disubstituted quinolines. This methodology provides an efficient strategy for the synthesis of diversely substituted quinolines, apart from Povarov reactions. Moreover, thisreaction has a broad substrate scope, and features inexpensive starting materials, mildconditions, as well as high atom efficiency.(2) Palladium-catalyzed selective oxidative cyclization of arylamines, aldehydes, andterminal olefins under molecular oxygen for the construction of a series of1,4-dihydropyridines. Preliminary exploration to synthesize unsymmetric1,4-dihydropyridineproduct was also made. Controlled experiments revealed that the (Z)-enamine was a keyintermediate of the reaction.(3) Palladium-catalyzed dehydrogenative aminohalogenation of alkenes with molecularoxygen as the sole oxidant. This protocol directly employs simple aromatic amines as thenitrogen sources, and provides highly convenient access to brominated enamine scaffoldunder mild conditions which was difficult to prepare by traditional methodologies, withunprecedented regio-and stereoselectivity as well as exceptional functional group tolerance.(4) Palladium-catalyzed oxidative coupling of aromatic primary amines and alkenesunder molecular oxygen. It provides an efficient access to (Z)-enamine compounds withexcellent regio-and stereoselectivity, and the resultant enamines could be convenientlytransformed into a series of N-containing heterocycles, such as indoles, pyrazoles, pyrroles,and1,4-dihydropyridines. The addition of LiBr was crucial to the success of thetransformation, due to its important role in avoiding the deactivation of palladium catalystarising from the strong coordination of aromatic primary amines to it.(5) Solvent-switched selectivity on palladium-catalyzed oxidative reactions involvingaromatic amines and alkenes. In the presence of30%H2O2as a co-oxidant, highly selectivedehydrogenative aminohalogenation of alkenes could be achieved with DMF as the solventunder molecular oxygen (1atm). On the other hand, highly selective bromination of aromaticamines and subsequent oxidative coupling with alkenes could be achieved with THF as thesolvent under similar conditions.