Rh-Catalyzed C-H Activation, [5 + 2] Cycloaddition/Oxidative for the Synthesis of Highly Functionalized
Bi Na Shao1, Jia-Qi Shao1, Qing-Sheng Zhao1
1Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, School of Chemical Science and Technology, Yunnan University, Kunming, 650091, P. R. China.
Abstract:
We developed a protocol for the synthesis of highly functionalized benzo[f]pyrazolo[1,5-a][1,3]diazepin-6-ones 3 (BPDOs) from 1-aryl-1H-pyrazol-5-amine derivatives using sulfoxonium ylides. This strategy involved Rh-catalyzed C-H activation and a rare [5 + 2] cycloaddition, with water participating in the capture of the intermediate to form an alcohol that is further oxidized into a seven-membered cyclic ketone structure, requiring the heating of a mixture of substrates 1 with 2 and isopropanol, catalyzed by [Cp*RhCl2]2, with Cu(OAc)2 and AgSbF6 acting as oxidants and anion exchange agents, and NaOAc serving as a buffering system. As a result, a series of BPDOs 3 were produced by forming three bonds (1 C-C, 1 C═N, and 1 C═O bond) in a single step. This protocol achieved an example of C-H bond activation forming a seven-membered cyclic structure with Rh(III). This strategy enables the synthesis of various rare complex structures, including polycyclic natural products with a benzo[1,3]diazepin-6-one scaffold, which offers a library of biologically active compounds accessible through combinatorial and parallel one-pot reactions.
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