Building C(sp 3)-rich complexity by combining cycloaddition and C–C cross-coupling reactions

Tie–Gen –G 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, Phil S. Baran

Research output: Contribution to journalLetter

19 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)350-354
Number of pages5
JournalNature
Volume560
Issue number7718
DOIs
StatePublished - Aug 16 2018
Externally publishedYes

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Cross Reactions
Cycloaddition Reaction
Drug Discovery
Carbon
Biological Products
Education

ASJC Scopus subject areas

  • General

Cite this

Chen, TG. G., Barton, L. M., Lin, Y., Tsien, J., Kossler, D., Bastida, I., ... Baran, P. S. (2018). Building C(sp 3)-rich complexity by combining cycloaddition and C–C cross-coupling reactions. Nature, 560(7718), 350-354. https://doi.org/10.1038/s41586-018-0391-9

Building C(sp 3)-rich complexity by combining cycloaddition and C–C cross-coupling reactions. / Chen, Tie–Gen –G; Barton, Lisa M.; Lin, Yutong; Tsien, Jet; Kossler, David; Bastida, Iñaki; Asai, Shota; Bi, Cheng; Chen, Jason S.; Shan, Mingde; Fang, Hui; Fang, Francis G.; Choi, Hyeong wook; Hawkins, Lynn; Qin, Tian; Baran, Phil S.

In: Nature, Vol. 560, No. 7718, 16.08.2018, p. 350-354.

Research output: Contribution to journalLetter

Chen, TGG, Barton, LM, Lin, Y, Tsien, J, Kossler, D, Bastida, I, Asai, S, Bi, C, Chen, JS, Shan, M, Fang, H, Fang, FG, Choi, HW, Hawkins, L, Qin, T & Baran, PS 2018, 'Building C(sp 3)-rich complexity by combining cycloaddition and C–C cross-coupling reactions', Nature, vol. 560, no. 7718, pp. 350-354. https://doi.org/10.1038/s41586-018-0391-9
Chen TGG, Barton LM, Lin Y, Tsien J, Kossler D, Bastida I et al. Building C(sp 3)-rich complexity by combining cycloaddition and C–C cross-coupling reactions. Nature. 2018 Aug 16;560(7718):350-354. https://doi.org/10.1038/s41586-018-0391-9
Chen, Tie–Gen –G ; Barton, Lisa M. ; Lin, Yutong ; Tsien, Jet ; Kossler, David ; Bastida, Iñaki ; Asai, Shota ; Bi, Cheng ; Chen, Jason S. ; Shan, Mingde ; Fang, Hui ; Fang, Francis G. ; Choi, Hyeong wook ; Hawkins, Lynn ; Qin, Tian ; Baran, Phil S. / Building C(sp 3)-rich complexity by combining cycloaddition and C–C cross-coupling reactions. In: Nature. 2018 ; Vol. 560, No. 7718. pp. 350-354.
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