Synthesis of 1-Aminoisoquinolines via Rh(III)-Catalyzed Oxidative Coupling

Abstract

ABSTRACT[RhCp*Cl 2 ] 2 can catalyze the oxidative coupling of N-aryl and N-alkyl benzamidines with alkynes to give N-substituted 1-aminoisoquinolines in high selectivity.Transition-metal catalyzed organic reactions via activation of CÀH bonds have attracted increasing attention. 1 This process is attractive in that CÀH bonds are ubiquitous and prefunctionalization of CÀH bonds is no longer necessary. Therefore, selective and efficient functionalization of CÀH bonds under mild conditions has been long sought, and this should allow the construction of complex molecules in an energy-efficient and step-economic fashion. Significant progresses have been made, and this topic has been extensively reviewed. 2 Among the various promising activation strategies is the utilization of a proximal directing group, which facilitates the activation of substrate ortho CÀH bonds. By utilizing this strategy with oxygen and nitrogen directing groups, rhodium complexes have stood out as efficient catalysts in the functionalization of CÀH bonds using unsaturated coupling partners. 3 Recently, Rh(III)-catalyzed oxidative CÀH functionalization of arenes with alkynes has been increasingly explored, which allowed for the synthesis of a broad spectrum of heterocycles. 4 A number of research groups, including ours, 5 have successfully applied this method to the synthesis of isoquinolines, 6 isoquinolones, 5c,7 indoles, 8 isocoumarins, 9 indenols, 4b,d pyrroles, 10 and pyridones. 5d,11 † The Chinese Academy of Sciences. ‡ Northwest Normal University.

Palladium-catalyzed selective oxidative olefination and arylation of 2-pyridones

“…Steric-assisted switch of reaction selectivity in rhodium-catalyzed C-H activation has been recently reported by us. 24 However, at this stage we cannot rule out the inductive effect of a 4-methyl group, which may also function toward the same direction by favoring migratory insertion of the 3-aryl group into an olefin. In contrast, no such cyclometalated intermediate will be generated when metalation occurs at the C(5) position.…”

Rh‐Catalyzed Synthesis of Nitrogen‐Containing Heterocycles

“…In 2011, Li et al described a Rh(III)-catalyzed coupling of N-aryl and N-alkyl benzamidines with internal alkynes that afforded less accessible 1-aminoisoquinolines 55 [30]. In the presence of ortho-substituted benzamidines, the reaction occurred by dual oxidative cyclization and furnished indole-isoquinoline 56.…”

Metal‐Free Facile Synthesis of Multisubstituted 1‐Aminoisoquinoline Derivatives with Dual‐State Emissions

“…This method used 1‐haloisoquinolines as the materials, which often suffered from the drawbacks of difficult to obtain raw materials, harsh reaction conditions, and tedious procedures. The other way was the recently popular metal‐catalyzed cross‐coupling methodology, which generally had high yields and extensive substrate adaptations . However, these kinds of reactions had the disadvantage of requiring the use of expensive and/or toxic metals catalysts.…”