para‐Selective Aerobic Oxidative CH Olefination of Aminobenzenes Catalyzed by Palladium/Molybdovanadophosphoric acid/2,4,6‐Trimethylbenzoic Acid System

Nitrogen-containing aromatic compounds bearing conjugated skeletons are useful intermediates in medicine, dye-sensitized solar cells, and photophysics. The introduction of alkenyl moieties in aminobenzenes is, therefore, an important chemical process. The Mizoroki–Heck reaction is a typical synthetic tool for the olefination of aromatic compounds. As a prerequisite of the conventional reaction is the use of aryl halides as substrates, this method suffers from the formation of undesired stoichiometric amounts of waste salts generated from aryl halides and bases. Pd-, Ru-, and Rh-catalyzed direct oxidative olefinations of arenes, which are referred to as direct Heck coupling, are currently a topic of intensive investigation. For selective direct olefination to be successful, a neighboring directing group to assist coordination to the metal catalyst is typically needed. In addition, the reaction is commonly performed under harsh conditions, using hazardous and toxic oxidants in acidic solvents such as acetic acid. Recent developments have resulted in the innovation of aerobic direct C H bond olefination using atmospheric molecular oxygen as a terminal oxidant. k, 4g, 5] In one of our most successful examples of aerobic direct Heck coupling, we found that a combination of molybdovanadophosphoric acid (HPMoV) and O2 serves as an efficient reoxidation system for Pd to Pd + ; this system is an efficient catalyst for the reaction of benzenes with olefins. These aerobic oxidative coupling protocols, which avoid the use of harsh oxidants, are beneficial from an environmental and atom-economical point of view. An unsolved problem still remains, however, with regard to these processes: the reactions are performed using acidic solvents, which hampers the use of a broad range of substrates, particularly basic aromatic compounds such as aminobenzenes. Until now, less basic acetanilides have been used as nitrogen-containing aromatic compounds in the direct C H olefination. c, e, g] The amide group on the phenyl ring serves as a directing group, and this reaction represents a general method for ortho-olefination of anilide derivatives. Recent research has shown that for direct C H olefinations of amides bearing N O bonds, the N O function acts as both a directing group and oxidant. Nevertheless, the direct C H olefination of basic substrates such as aminobenzenes remains underdeveloped because of the current need to use acidic solvents. The use of basic substrates tends to result in loss of catalytic activity. Indeed, van Leeuwen, de Vries and coworkers showed that acetanilides are very effective substrates for oxidative olefination using Pd(OAc)2 combined with benzoquinone and p-toluenesulfonic acid (p-TsOH) in acetic acid. They also reported, however, that no coupling products were obtained with aminobenzenes such as N,N-dialkylanilines under these conditions. The reaction of aminobenzene with ethyl acrylate was totally inactive under conditions using the Pd(OAc)2/HPMoV/O2 catalytic system in acetic acid developed in our laboratory for aerobic direct C H olefination of arenes (Scheme 1 a).