Transition-metal-free access to primary anilines from boronic acids and a common (+)NH2 equivalent

Abstract

Diversely substituted anilines are prepared by treatment of functionalized arylboronic acids with a common, inexpensive source of electrophilic nitrogen (H2N-OSO3H, HSA) under basic aqueous conditions. Electron-rich substrates are found to be the most reactive by this method. However, even moderately electron-poor substrates are well tolerated under the room temperature conditions. Sterically hindered substrates appear to be equally effective compared to unhindered ones. Highly electron-deficient substrates afford product in very low yields at room temperature, but moderate to good yields are obtained at refluxing temperatures. Our method is also amenable to electrophilic amination of several common boronic acid derivatives (e.g., pinacol esters). We demonstrate that it can be combined with metal-halogen exchange reactions or a variety of directed ortho metalation protocols in a "one-pot" sequence for the synthesis of aromatic amines with unique substitution patterns. DFT studies, in combination with experimental results, suggest that the reaction occurs via base-mediated activation of HSA, followed by 1,2 aryl B-N migration. This mode of activation appears to be critical for the success of the reaction and allows, for the first time, a general, electrophilic amination of boronic acids at ambient temperature.