Iridium-Catalyzed Direct Ortho-C-H Amidation Of Benzoic Acids With Sulfonylazides

C-N bond construction has been one of the most important research topics in organic synthesis, accompanied by the development of Ullmann reaction and Buchwald-Hartwig amination. However, their high cost and environmental toxicity, such as stoichiomeric amounts of halogen salt as by-product, prevent the large-scale syntheses in industrial applications. Recently, the direct C-H bond functionalization has been more facility, straightforward and environment friendly protocols to construct carbon-carbon and carbon-heteroatom bonds. However, most of transition-metal-catalyzed C-H amination reactions require stoichiometric external oxidants and the harsh reaction conditions. Organic azides, which is an environmental amino source and also as an internal oxidant via N-N₂ bond cleavage, would be key to develop an efficient C-H amination and the sole byproduct is molecular nitrogen（N₂）. Recently, a series of azide as a nitrogen source amine reaction has been reported by Chang’s group. Directing group（such as: pyridine, amide, ketone, oxime） oriented C-H bond activation reaction has been reported by Chemists.Along with our continuing efforts to explore novel C-N bond formations, we herein independently reported an iridium-catalyzed carboxylic acid-directed C-H aminations with sulfonyl azides as amino sources, which afforded sulfonamide and anthranilic acid derivatives. This reaction system is simple and efficient, low reaction temperature, without an external oxidant, atom economy, environment-friendly, molecular nitrogen as the only byproduct. The protocol exhibited a broad substrate scope and proceeded under mild conditions with excellent functional group tolerance. Notably, the products obtained from this protocol as an important structural units, which widely exist in pharmaceutical molecules and natural products, such as the potent inhibitor of methionine aminopeptidase-2（MetAP-2）, and sulfonamide derivatives with efficiently anti-inflammatory and aldose reductase inhibitory activities.