Studies Of Palladium-catalyzed Dual C-H Bond Activation And [4+2] Cycloaddition For Synthesis Of Quinoline Derivatives

Recently, transition-metal catalyzed coupling reactions for the construction ofC-C bonds via direct C-H bond activation have been intensively investigated. In viewof green and sustainable chemistry, cross-coupling reactions utilizing dual C-H bondactivations to give the corresponding biaryl products would seem ideal. However, theintramolecular C-C coupling reactions through the activation of two C-H bondsdirected by a group are relatively rare. The activation of two C-H bonds in onemolecular requires the directing group locating in a suitable position in order to formstable metallacycle intermediates, which is difficult to realized due to spacelimitations of special geometry. Here, we describe an effective catalytic system for theintramolecular dual C-H activations. In this system, Pd(OAc)2was used as the catalyst,Cu(OAc)2·H2O as a co-oxidant, oxygen as a terminal oxidant, diphenylacetic acid andtheir derivatives as substrates. The carboxyl, as a removable directing group, plays animportant role in the dual C-H activations of the substrate. The current methodprovides an efficient synthetic route for a variety of substituted fluorenones undermild reaction conditions.Quinoline and its derivatives are important skeletons in numerous organiccompounds, many of which have wide applications in all areas. In the past decades,one of the most popular methods for the synthesis of quinoline derivatives is that useaniline compounds as the starting material, occurred a series of reactions. However,this method involves harsh reaction conditions, strong acids and a high reactiontemperature, which limits the use of this method. We describe here a [4+2]-typecycloaddition reaction of o-nitrotoluenes bearing electron withdrawing groups andα,β-unsaturated compounds, such as ethyl acrylate or acrylonitrile in the presence of abase. In this reaction, the base was demonstrated to be an essential component. Thisreaction allows a modular atom economic synthesis of a variety of functionalizedquinolines directly from substituted o-nitrotoluenes under mild conditions.