Most of the metal-catalyzed C–H activation/annulation reactions were carried out in organic solvents using expensive oxidants such as Cu(II) and Ag(I) salts. Here, we reported a new approach for a highly regioselective synthesis of isoquinolones from N-alkyl benzamides and alkynes using an Rh(III) catalyst and inexpensive oxygen as the sole oxidant in an aqueous medium. In the reaction, water gave the highest product yield among the solvents used. In addition, at the end of the reaction, the isoquinolone product directly precipitated out from the aqueous solution. The methodology can be applied to a gram scale synthesis. This Rh(III)-catalyzed reaction shows interesting meta selectivity with the meta substituted benzamide and shows various regioselectivities with different substituted alkynes. Moreover, the methodology can be applied to the preparation of biologically active compounds having the isoquinolone core.

Various substituted indolizidinium, quinolizinium and pyrido[1,2-a]azepinium salts synthesized from benzaldehydes (or α,β-unsaturated aldehydes) and alkyne–amines catalyzed by rhodium complexes via C–H activation are demonstrated. The reaction was carried out under mild reaction conditions using Cu(BF₄)₂·6H₂O as oxidant and anion source and inexpensive oxygen as a co-oxidant. A reaction mechanism involving imine formation followed by an ortho C–H activation, alkyne insertion and reductive elimination via a 7-membered rhodacycle is proposed. The present method has been successfully applied to the synthesis of a natural product, ficuseptine.