Transition Metal-catalyzed Alpha-ketoimino Csp~3-H Bond Functionalization

N-Heteroarenes represent a general scaffold which could be found in many natural products, drugs and other functional materials. Therefore, it is important to develop efficient methods for constructing these compounds. Among the various strategies to prepare N-heteroarenes, transition-metal-catalyzed C-H bond activation procedure is emerging as an ideal strategy due to its atom- and step-economy. In view of the smart reactivity of imines, the construction of C-N bond derived from imines has been widely investigated via n + 2 cyclization reactions, Diels-Alder reactions, nucleophilic reactions and radical reactions. However, transition-metal-catalyzed alpha-imino Csp3–H bond functionalizations have been rarely reported, which could possibly provide a powerful tool to construct various N-Heteroarenes. Herein, we reported a novel transition-metal catalyzed chelation-assisted functionalization of ?-imino Csp3-H bond to synthesize N-heterocycles, and the main works are shown as follows.Initially, given that 2-pyridyl-substituted enamine intermediates derived from imine/enamine isomerization under the transition-metal catalyst could form metallacyclic intermediates via C-H activation process, and the corresponding metallacyclic intermediates could be possibly trapped by alkynes to form new C – X bond(X= C and N). Therefore, we have developed a Pd(II)-catalyzed oxidative [3+2] cycloaddition reaction between N-(2-pyridyl)-substituted ketoimines and internal alkynes to assemble multisubstituted pyrroles through the chelation-assisted Csp3-H functionalization of pyridyl group. This transformation tolerates a variety of useful functionalities including halogen, hydroxyl, alkyloxycarbonyl, etc., which could be further converted to other synthetically useful pyrrole derivatives. The corresponding control experiments were performed and indicated that the pyridyl group acted a significant directing role for this reaction. Finally, the intermolecular isotope effect(KIE = 1.59) implied alpha-imino Csp3–H bond cleavage was possibly involved in the rate-limiting step.Considering that carbon monoxide also belongs to an important unsaturated C1 source and in connection with our previous work, we envisioned that the fore-mentioned six-membered cyclopalladium intermediate will be possibly trapped by unsaturated carbon atom-containing CO via the carbonyl insertion process, and result in the occurrence of a carbonylation reaction. After initial reaction condition screening, we found that N-(2-pyridyl) ketoimines could react with CO(1 atm) under a Pd(II)/Cu(II)/KI system to form pyrido[1,2-a]pyrimidin-4-ones in moderate to excellent yields. The further examination of the scope and limitations of the pyridine-directed carbonylation reaction indicated that electron-rich ketoimines offered a higher yield of products except N-(3-methoxylpyridine)-substituted ketoimine with a stronger steric hindrance. Furthermore, we proposed a possible mechanism based on the results of several controlled experiments and kinetic isotope effect experiments.Finally, Designing and synthesizing novel organic conjugated monomer with excellent electrochemical and photochemical properties become one of the most attractive research areas in materials chemistry. Considering that C-H bond activation can site-selectively introduce particular functional group into target molecules, we employed this synthetic strategy to investigate Rh(III)-catalyzed double C-H functionalization between N-phenyl-ketoimines and diazoesters for rapid assembly of highly extended π-conjugated 1-azaphenalene derivatives through C-C and C-N bond formations via one reaction step. Moreover, the cross-coupling of ketoimines with different diazoesters could be allowed for constructing multisubstituted 1-azaphenalene derivatives. Meanwhile, we also found the cyclic voltammogram(CV) curves from 1-azaphenalene-based π-conjugated molecules possessed low-lying HOMO energy level(-5.76 eV ~-5.57 eV). This property implies that 1-azaphenalene-based acceptor monomer could be further assembly high-performance organic optoelectronic materials.