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Synfacts 2023; 19(10): 0989
DOI: 10.1055/s-0042-1752185
Metals in Synthesis

Copper-Catalyzed Difluoroalkylation of Silyl-Enol Ethers

Contributor(s):
Mark Lautens
,
Alexa Torelli
Zeng X, Li Y, Min Q.-Q, Xue X.-S, *, Zhang X. * Shanghai Institute of Organic Chemistry, P. R. of China
Copper-Catalyzed Difluorocarbene Transfer Enables Modular Synthesis.

Nat. Chem. 2023;
15: 1064-1073
DOI: 10.1038/s41557-023-01236-8
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Key words

copper catalysis - fluorination - carbenes

Significance

A copper-catalyzed difluorocarbene transfer reaction is reported. This strategy couples a difluorocarbene, generated from a bromodi­fluoroacetate precursor, with two inexpensive feedstocks. A silyl enol ether and allyl/propargyl bromides engage to access difluoroalkylated compounds in up to 95% yield. A broad substrate scope features a range of cyclic and acyclic silyl enol ethers and differently substituted allyl ­bromides. The methodology is also efficient when applied in a gram-scale reaction.


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Comment

Mechanistic and computational studies were used to elucidate the mechanism. The reaction of the copper(I) salt and the in situ generated difluorocarbene generates the isolable electrophilic carbene A. Subsequent nucleophilic addition (B), and desilylation generates difluoro­alkylcopper species C. Oxidative addition of C with the allyl halide and then reductive elimination delivers the product.


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Publication History

Article published online:
14 September 2023

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