Organic azides RN3 are widely used in the field of C-H amination due to their ability to form reactive nitrene intermediates [M]=NR in the presence of a metal catalyst [M]. Our laboratory has largely focused on the use of aryl- and alkylazides RN3 in conjunction with β-diketiminato copper catalysts [Cu] that give rise to dicopper nitrenes [Cu]2(μ-NR) that perform C-H amination via terminal [Cu]=NR intermediates. Since C-H amination of substrates R’-H proceeds via H-atom transfer (HAT) to form [Cu]-NHR and radicals R’ dot, we are eager to enhance the driving force of this HAT reaction for synthetic advantage. Noting that carbonyl azides RC(O)N3 and sulfonyl azides RSO2N3 are derived from organic amides RC(O)NH2 and RSO2NH2 that possess higher N-H bond strengths than their aryl- and alkylamine counterparts RNH2, we have begun to methodically survey the use of RC(O)N3 and RSO2N3 reagents with β-diketiminato copper(I) catalysts. In contrast to simple organoazides RN3, use of RC(O)N3 and RSO2N3 nitrene sources does not lead to easily isolable copper nitrenes [Cu]2(μ-NR). Rather, highly reactive intermediates result capable of sp3 C-H amidation under mild conditions. We will outline factors that lead to efficient sp3 C-H amidation with limiting use of the C-H substrates, allowing the use of these protocols for the late stage elaboration of more complex C-H substrates.

Copper catalyzed C-H amidation

254th National Meeting (2017)

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