Chemo- and regioselective benzylic C(sp3)-H oxidation bridging the gap between hetero- and homogeneous copper catalysis

iScience. 2022 May 2;25(5):104341. doi: 10.1016/j.isci.2022.104341. eCollection 2022 May 20.


Selective C‒H functionalization in a pool of proximal C‒H bonds, predictably altering their innate reactivity is a daunting challenge. We disclose here, an expedient synthesis of privileged seven-membered lactones, dibenzo[c,e]oxepin-5(7H)-one through a highly chemoselective benzylic C(sp3)‒H activation. Remarkably, the formation of widely explored six-membered lactone via C(sp2)‒H activation is suppressed under the present conditions. The reaction proceeds smoothly on use of inexpensive metallic copper catalyst and di-tert-butyl peroxide (DTBP). Owing to the hazards of stoichiometric DTBP, further, we have developed a sustainable metallic copper/rose bengal dual catalytic system coupled with molecular oxygen replacing DTBP. A 1,5-aryl migration through Smiles rearrangement was realized from the corresponding diaryl ether substrates instead of expected eight-membered lactones. The present methodology is scalable, applied to the total synthesis of cytotoxic and neuroprotective natural product alterlactone. The catalyst is recyclable and the reaction can be performed in a copper bottle without any added catalyst.

PMID:35602936 | PMC:PMC9118691 | DOI:10.1016/j.isci.2022.104341


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