Chan-Lam animation studies : solving the chemotype reactivity issue

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The work presented in this thesis describes the study of the Chan-Lam reaction between aryl boronic acid pinacol esters (BPin) and alkyl and aryl amines. Firstly, we developed an effective stoichiometric set of reaction conditions for the Chan-Lam amination of aryl BPin with alkyl and aryl amines. A mixed MeCN/EtOH solvent system was found to enable effective C−N bond formation using aryl amines while EtOH is not required for the coupling of alkyl amines. Secondly, we investigated the Chan–Lam amination reaction using a combination of spectroscopy, computational modeling, and crystallography techniques. We provided a full mechanistic description including the source of the boronic acid pinacol ester reactivity issue, determining the origin of amine chemotype reactivity and side reaction issues, identifying key reactive intermediates, and demonstrating the pivotal role of boron-based by-products. Finally, manipulating Cu(I) → Cu(II) reoxidation and exploiting three synergistic roles of boric acid has allowed the development of a general catalytic Chan–Lam amination, overcoming long-standing and unsolved amine and organoboron limitations of this valuable transformation. [See thesis abstract for illustrative figures]

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