Building C(sp3)-rich complexity by combining cycloaddition and C–C cross-coupling reactions

Tie–Gen Chen, Lisa M. Barton, Yutong Lin, Jet Tsien, David Kossler, Iñaki Bastida, Shota Asai, Cheng Bi, Jason S. Chen, Mingde Shan, Hui Fang, Francis G. Fang, Hyeong-wook Choi, Lynn Hawkins, Tian Qin and Phil S. Baran ()
Additional contact information
Tie–Gen Chen: The Scripps Research Institute (TSRI)
Lisa M. Barton: The Scripps Research Institute (TSRI)
Yutong Lin: The Scripps Research Institute (TSRI)
Jet Tsien: The Scripps Research Institute (TSRI)
David Kossler: The Scripps Research Institute (TSRI)
Iñaki Bastida: The Scripps Research Institute (TSRI)
Shota Asai: The Scripps Research Institute (TSRI)
Cheng Bi: The Scripps Research Institute (TSRI)
Jason S. Chen: The Scripps Research Institute (TSRI)
Mingde Shan: Eisai AiM Institute
Hui Fang: Eisai AiM Institute
Francis G. Fang: Eisai AiM Institute
Hyeong-wook Choi: Eisai AiM Institute
Lynn Hawkins: Eisai AiM Institute
Tian Qin: The Scripps Research Institute (TSRI)
Phil S. Baran: The Scripps Research Institute (TSRI)

Nature, 2018, vol. 560, issue 7718, 350-354

Abstract: Abstract Prized for their ability to rapidly generate chemical complexity by building new ring systems and stereocentres1, cycloaddition reactions have featured in numerous total syntheses2 and are a key component in the education of chemistry students3. Similarly, carbon–carbon (C–C) cross-coupling methods are integral to synthesis because of their programmability, modularity and reliability4. Within the area of drug discovery, an overreliance on cross-coupling has led to a disproportionate representation of flat architectures that are rich in carbon atoms with orbitals hybridized in an sp2 manner5. Despite the ability of cycloadditions to introduce multiple carbon sp3 centres in a single step, they are less used6. This is probably because of their lack of modularity, stemming from the idiosyncratic steric and electronic rules for each specific type of cycloaddition. Here we demonstrate a strategy for combining the optimal features of these two chemical transformations into one simple sequence, to enable the modular, enantioselective, scalable and programmable preparation of useful building blocks, natural products and lead scaffolds for drug discovery.

Date: 2018
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41586-018-0391-9 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:560:y:2018:i:7718:d:10.1038_s41586-018-0391-9

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

DOI: 10.1038/s41586-018-0391-9

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 ().