Ni-electrocatalytic Csp3–Csp3 doubly decarboxylative coupling

Benxiang Zhang, Yang Gao, Yuta Hioki, Martins S. Oderinde, Jennifer X. Qiao, Kevin X. Rodriguez, Hai-Jun Zhang, Yu Kawamata and Phil S. Baran ()
Additional contact information
Benxiang Zhang: Scripps Research
Yang Gao: Scripps Research
Yuta Hioki: Scripps Research
Martins S. Oderinde: Bristol Myers Squibb, Research & Early Development
Jennifer X. Qiao: Bristol Myers Squibb Company
Kevin X. Rodriguez: Scripps Research
Hai-Jun Zhang: Scripps Research
Yu Kawamata: Scripps Research
Phil S. Baran: Scripps Research

Nature, 2022, vol. 606, issue 7913, 313-318

Abstract: Abstract Cross-coupling between two similar or identical functional groups to form a new C–C bond is a powerful tool to rapidly assemble complex molecules from readily available building units, as seen with olefin cross-metathesis or various types of cross-electrophile coupling1,2. The Kolbe electrolysis involves the oxidative electrochemical decarboxylation of alkyl carboxylic acids to their corresponding radical species followed by recombination to generate a new C–C bond3–12. As one of the oldest known Csp3–Csp3 bond-forming reactions, it holds incredible promise for organic synthesis, yet its use has been almost non-existent. From the perspective of synthesis design, this transformation could allow one to agnostically execute syntheses without regard to polarity or neighbouring functionality just by coupling ubiquitous carboxylates13. In practice, this promise is undermined by the strongly oxidative electrolytic protocol used traditionally since the nineteenth century5, thereby severely limiting its scope. Here, we show how a mildly reductive Ni-electrocatalytic system can couple two different carboxylates by means of in situ generated redox-active esters, termed doubly decarboxylative cross-coupling. This operationally simple method can be used to heterocouple primary, secondary and even certain tertiary redox-active esters, thereby opening up a powerful new approach for synthesis. The reaction, which cannot be mimicked using stoichiometric metal reductants or photochemical conditions, tolerates a range of functional groups, is scalable and is used for the synthesis of 32 known compounds, reducing overall step counts by 73%.

Date: 2022
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-022-04691-4 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:606:y:2022:i:7913:d:10.1038_s41586-022-04691-4

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-022-04691-4

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().