Abstract
In contrast to the rapidity with which scientific information is published, the application of new knowledge often remains slow, and we believe this to be particularly true of newly developed synthetic organic chemistry methodology. Consequently, methods to assess and identify robust chemical reactions are desirable, and would directly facilitate the application of newly reported synthetic methodology to complex synthetic problems. Here, we describe a simple process for assessing the likely scope and limitations of a chemical reaction beyond the idealized reaction conditions initially reported. Using simple methods and common analytical techniques we demonstrate a rapid assessment of an established chemical reaction, and also propose a simplified analysis that may be reported alongside new synthetic methodology.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Seebach, D. Organic synthesis—where now? Angew. Chem. Int. Ed. Engl. 29, 1320–1367 (1990).
Newhouse, T., Baran, P. S. & Hoffmann, R. W. The economies of synthesis. Chem. Soc. Rev. 38, 3010–3021 (2009).
Trost, B. M. The atom economy—a search for synthetic efficiency. Science 254, 1471–1477 (1991).
Trost, B. M. Selectivity: a key to synthetic efficiency. Science 219, 245–248 (1983).
Trost, B. M. Atom economy. A challenge for organic synthesis. Angew. Chem. Int. Ed. Engl. 34, 259–281 (1995).
Wender, P. A. & Miller, B. L. Synthesis at the molecular frontier. Nature 460, 197–201 (2009).
Horvàth, I. & Anastas, P. T. Innovations and green chemistry. Chem. Rev. 107, 2169–2173 (2007).
Nadin, A., Hattotuwagama, C. & Churcher, I. Lead-oriented synthesis: a new opportunity for synthetic chemistry. Angew. Chem. Int. Ed. 51, 1114–1122 (2012).
Nicolaou, K. C., Vourloumis, D., Winssinger, N. & Baran, P. S. The art and science of total synthesis at the dawn of the twenty-first century. Angew. Chem Int. Ed. 39, 44–122 (2000).
Müller, T. J. J. & Bunz, U. H. F. Functional Organic Materials: Syntheses, Strategies and Applications (Wiley, 2007).
Li, J. J. & Johnson, D. S. Modern Drug Synthesis (Wiley, 2010).
Lamberth, C. & Dinges, J. Bioactive Heterocyclic Compound Classes: Pharmaceuticals and Agrochemicals (Wiley-VCH, 2012).
Miyaura, N. & Suzuki, A. Palladium-catalyzed cross-coupling reactions of organoboron compounds. Chem. Rev. 95, 2457–2483 (1995).
Baidya, M., Griffin, K. A. & Yamamoto, H. Catalytic enantioselective O-nitrosocarbonyl aldol reaction of β-dicarbonyl compounds. J. Am. Chem. Soc. 134, 18566–18569 (2012).
Wencel-Delord, J., Nimphius, C., Wang, H. & Glorius, F. Rhodium(III) and hexabromobenzene—a catalyst system for the cross-dehydrogenative coupling of simple arenes and heterocycles with arenes bearing directing groups. Angew. Chem. Int. Ed. 51, 13001–13005 (2012).
Wang, H., Grohmann, C., Nimphius, C. & Glorius, F. Mild rhodium(III)-catalyzed C–H activation and annulation with alkyne MIDA boronates: short and efficient synthesis of heterocyclic boronic acid derivatives. J. Am. Chem. Soc. 134, 19592–19595 (2012).
Burns, A. R., González, J. S. & Lam, H. W. Enantioselective copper(I)-catalyzed borylative aldol cyclizations of enone diones. Angew. Chem. Int. Ed. 51, 10827–10831 (2012).
Guram, A. S., Rennels, R. A. & Buchwald, S. L. A simple catalytic method for the conversion of aryl bromides to arylamines. Angew. Chem. Int. Ed. Engl. 34, 1348–1350 (1995).
Louie, J. & Hartwig, J. F. Palladium-catalyzed synthesis of arylamines from aryl halides mechanistic studies lead to coupling in the absence of tin reagents. Tetrahedron Lett. 36, 3609–3612 (1995).
Robbins, D. W. & Hartwig, J. F. A simple, multidimensional approach to high-throughput discovery of catalytic reactions. Science 333, 1423–1427 (2011).
McNally, A., Prier, C. K. & MacMillan, D. W. C. Discovery of an α-amino C–H arylation reaction using the strategy of accelerated serendipity. Science 334, 1114–1117 (2011).
Acknowledgements
Dedicated to Prof. R. W. Hoffmann on the occasion of his 80th birthday. The authors acknowledge financial support from the European Research Council under the European Community's Seventh Framework Program (FP7 2007–2013)/ERC Grant agreement (no. 25936) and the Deutsche Forschungsgemeinschaft (DFG, Leibniz award to F.G.). The authors thank C. Richter and D. Tang for helpful discussions.
Author information
Authors and Affiliations
Contributions
F.G. and K.D.C. conceived the concept and experiments. K.D.C. performed all experiments. Both authors discussed the results and co-wrote the paper.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Supplementary information
Supplementary information
Supplementary information (PDF 1725 kb)
Rights and permissions
About this article
Cite this article
Collins, K., Glorius, F. A robustness screen for the rapid assessment of chemical reactions. Nature Chem 5, 597–601 (2013). https://doi.org/10.1038/nchem.1669
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/nchem.1669
