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Copper-catalyzed intermolecular C(sp3)-H bond functionalization towards the synthesis of tertiary carbamates
Prasanna Kumara Chikkade1, Yoichiro Kuninobu1,2, Motomu Kanai1,2
1Graduate School of Pharmaceutical Sciences , The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku , Tokyo 113-0033 , Japan . Email: kuninobu@mol.f.u-tokyo.ac.jp ;
Abstract:
We describe the development of an intermolecular unactivated C(sp3)-H bond functionalization towards the direct synthesis of tertiary carbamates. The transformation proceeded using a readily available, abundant first-row transition metal catalyst (copper), and isocyanates as the source of the amide moiety. This is a novel strategy for direct transformation of a variety of unactivated hydrocarbon feedstocks to N-alkyl-N-aryl and N,N-dialkyl carbamates without pre-functionalization or installation of a directing group. The reaction had a broad substrate scope with 3° > 2° > 1° site selectivity. The reaction proceeded even on a gram scale, and a corresponding free amine was directly obtained when the reaction was performed at high temperature. Kinetic studies suggested that radical-mediated C(sp3)-H bond cleavage was the rate-determining step.
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