Author
Listed:
- Benxiang Zhang
(Scripps Research)
- Jiayan He
(Scripps Research)
- Yang Gao
(Scripps Research)
- Laura Levy
(Scripps Research)
- Martins S. Oderinde
(Bristol Myers Squibb Research & Early Development)
- Maximilian D. Palkowitz
(Bristol Myers Squibb Research & Early Development)
- T. G. Murali Dhar
(Bristol Myers Squibb Research & Early Development)
- Michael D. Mandler
(Bristol Myers Squibb Research & Early Development)
- Michael R. Collins
(Pfizer Pharmaceuticals)
- Daniel C. Schmitt
(Pfizer Worldwide Research and Development
Eli Lilly and Company)
- Philippe N. Bolduc
(Biogen Inc.)
- TeYu Chen
(Biogen Inc.)
- Sebastian Clementson
(LEO Pharma A/S)
- Nadia Nasser Petersen
(LEO Pharma A/S)
- Gabriele Laudadio
(Scripps Research)
- Cheng Bi
(Scripps Research)
- Yu Kawamata
(Scripps Research)
- Phil S. Baran
(Scripps Research)
Abstract
Modern retrosynthetic analysis in organic chemistry is based on the principle of polar relationships between functional groups to guide the design of synthetic routes1. This method, termed polar retrosynthetic analysis, assigns partial positive (electrophilic) or negative (nucleophilic) charges to constituent functional groups in complex molecules followed by disconnecting bonds between opposing charges2–4. Although this approach forms the basis of undergraduate curriculum in organic chemistry5 and strategic applications of most synthetic methods6, the implementation often requires a long list of ancillary considerations to mitigate chemoselectivity and oxidation state issues involving protecting groups and precise reaction choreography3,4,7. Here we report a radical-based Ni/Ag-electrocatalytic cross-coupling of substituted carboxylic acids, thereby enabling an intuitive and modular approach to accessing complex molecular architectures. This new method relies on a key silver additive that forms an active Ag nanoparticle-coated electrode surface8,9 in situ along with carefully chosen ligands that modulate the reactivity of Ni. Through judicious choice of conditions and ligands, the cross-couplings can be rendered highly diastereoselective. To demonstrate the simplifying power of these reactions, concise syntheses of 14 natural products and two medicinally relevant molecules were completed.
Suggested Citation
Benxiang Zhang & Jiayan He & Yang Gao & Laura Levy & Martins S. Oderinde & Maximilian D. Palkowitz & T. G. Murali Dhar & Michael D. Mandler & Michael R. Collins & Daniel C. Schmitt & Philippe N. Boldu, 2023.
"Complex molecule synthesis by electrocatalytic decarboxylative cross-coupling,"
Nature, Nature, vol. 623(7988), pages 745-751, November.
Handle:
RePEc:nat:nature:v:623:y:2023:i:7988:d:10.1038_s41586-023-06677-2
DOI: 10.1038/s41586-023-06677-2
Download full text from publisher
As the access to this document is restricted, you may want to search for a different version of it.
Corrections
All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:623:y:2023:i:7988:d:10.1038_s41586-023-06677-2. See general information about how to correct material in RePEc.
If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.
We have no bibliographic references for this item. You can help adding them by using this form .
If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.
For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .
Please note that corrections may take a couple of weeks to filter through
the various RePEc services.