New Paradigms for C-N Bond Formation Featuring Imidazole-Selective Hydroamination and Metal-Catalyzed C-N Cross-Coupling Reactions

Abstract

Nitrogen containing organic compounds are substantially significant due to their existence in many biologically active natural products, pharmaceuticals and agrochemicals. Intensive research in the introduction of amino group has receiving huge attention over the past few decades. Despite the extensive progress has been made, numerous research groups are still eager to construct C-N bond through innovative and sustainable synthetic pathway. Hydroamination is one that emphasized as sustainable and atom-economical C-N bond forming process prerequisite to additives such as metal catalyst, organic or inorganic base. Recently, we have discovered an unprecedented imidazole-selective alkyne intermolecular hydroamination reaction under additive-free mild conditions. The reaction proceeds at ambient temperature with outstanding regio- and stereo- selectivity. Based on our extensive study on scope of the reaction and kinetic experiments, we have addressed a conceivable reaction mechanism. Furthermore, we have designed a suitable sensor for detection and quantitation of imidazole containing molecules. We have also investigated ring-size dependent copper assisted post-Ullmann C-N cross-coupling reaction with various cyclic enol triflates. This work is the extension of our former work of palladium catalysis that limited to smaller ring size enol triflate. The copper mediated coupling reaction revealed the reversed outcome compare to former study, and our novel method were optimized in stoichiometric and catalytic processes. Due to the surprising reversed outcomes, we have done comparative study on the Pd and Cu assisted coupling reaction via DFT (Density Functional Theory) calculation.