Rhodium(III)-Catalyzed C-H/O2 Dual Activation and Macrocyclization: Synthesis and Evaluation of
Bichao Song1,2, Xueying Guo3, Li Yang1,2
1State key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
Abstract:
The development of environment-friendly, step economic couplings to generate structurally diverse macrocyclic compounds is highly desirable but poses a marked challenge. Inspired by the C-H oxidation mechanism of cytochromes P450, an unprecedented and practical RhIII -catalyzed acylmethylation macrocyclization via C-H/O2 dual activation has been developed by us. The process of macrocyclization is facilitated by a synergic coordination from pyridine and ester group. Interestingly, the reaction mode derives from a three-component coupling which differs from established olefination and alkylation paths. Density functional theory (DFT) calculations and control experiments revealed the mechanism of this unique C-H/O2 dual activation. The newly achieved acylmethylation macrocyclic products and their derivatives showed a potent anti-H1N1 bioactivity, which may provide an opportunity for the discovery of novel anti-H1N1 macrocyclic leading compounds.
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