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Synfacts 2025; 21(01): 39
DOI: 10.1055/a-2467-4559
Metals in Synthesis

Dual-Metal-Catalyzed Synthesis of Fused Quinolin-2(1H)-one Scaffolds

Contributor(s):
Mark Lautens 
,
Alexa Torelli
Li S, Wang L, Wang S, Ying J *. Zhejiang Sci-Tech University, Hangzhou, P. R. China
Tandem Synthesis of 3,5-Dihydrocyclopenta[de]quinolin-2(H)-One Scaffolds from α-Bromocarbonyls and α-Diazoesters Under Copper and Palladium Catalysis.

Adv. Synth. Catal. 2024;
DOI: 10.1002/adsc.202401024
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Keywords

copper catalysis - palladium catalysis - heterocycle synthesis

Significance

Fused quinolin-2(1H)-ones are a common structural motif in many natural products and bioactive compounds. Ying and colleagues report a tandem copper/palladium-catalyzed cyclization and C–H activation/carbene insertion of α-bromocarbonyls with α-diazoesters, providing access to 3,5-dihydrocyclopenta[de]quinolin-2(1H)-one derivatives. The authors report synthetically useful yields across a range of aryl diazoesters with different electronic and steric properties. Various functionalized aryl alkynes are well tolerated under the reaction conditions; however, they note that alkyl alkynes are unreactive.


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Comment

Based on mechanistic studies, a plausible reaction pathway is proposed. First, a Cu(I)-mediated single-electron transfer (SET) of the α-bromocarbonyl initiates an intramolecular radical addition to the alkyne. Radical quenching by the Cu(II)Br species regenerates the copper catalyst and forms alkenyl bromide intermediate A. Intermediate A enters the Pd(0)/(II) catalytic cycle, starting with oxidative addition. In the presence of a base, C–H activation occurs to form palladacycle C. This species reacts with the diazoester, generating D. Following migratory insertion (E) and reductive elimination, the final product is obtained.


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Publication History

Article published online:
20 December 2024

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