Metal-Free Oxidative Biaryl Coupling by Hypervalent Iodine Reagents

In green chemistry, the most ideal synthetic route to biaryl compounds, which are important in manufacturing fine chemicals, from non-functionalized starting aromatic materials appears to be the oxidative couplings that directly use two molecules of C-H groups for a new bond-forming event to reduce the synthetic steps and by-product generation. However, these methods for reacting non-activated aromatic substrates are known to have difficulty in achieving selective cross-biaryl-couplings because of the over-oxidation of the products and competitive homodimer formations by undesired coupling between the same aryl substrates. In order to realize an efficient cross-coupling, therefore, unique chemoselective nature of the oxidant for the aromatic rings that discriminate aromatic substrates is required together with the sufficient oxidation ability. Using hypervalent iodine reagent, we have recently pioneered a number of new metal-free oxidative aromatic coupling methods for providing several types of mixed biaryls in high yields with perfect cross-coupling selectivities. They are classified into three types of the aromatic ring activation modes based on the pattern of the reaction mechanisms, which involve i) the aromatic cation radicals, ii) diaryliodonium salts, and iii) C-reactive phenoxenium ions and their N-analogues. As a result, the strategies now cover a wide range of the aromatic substrates. Hypervalent iodine reagents having low toxicities, mild reactivities, ready availability, high stabilities, easy handling, and ease of recovery and recyclability are useful alternatives to metal-based oxidants and catalysts for performing metal-free synthesis. We fully summarize the outcomes and clarify the synthetic values of our hypervalent iodine methods among the oxidative cross-coupling area.