A multi-substrate screening approach for the identification of a broadly applicable Diels–Alder catalyst

• Published in: Nature communications Vol. 10; no. 1; p. 770
• Main Authors: Kim, Hyejin, Gerosa, Gabriela, Aronow, Jonas, Kasaplar, Pinar, Ouyang, Jie, Lingnau, Julia B., Guerry, Paul, Farès, Christophe, List, Benjamin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15.02.2019; Nature Publishing Group; Nature Portfolio
• Subjects: 639/638/403/605; 639/638/77/883; 639/638/77/889; Acids; Aldehydes; Chemical reactions; Chemists; Chromatography; Cyclopentadiene; Humanities and Social Sciences; Methodology; multidisciplinary; Organic chemistry; Science; Science (multidisciplinary); Screening; Stereoselectivity; Substrates
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-08374-z

When developing a synthetic methodology, chemists generally optimize a single substrate and then explore the substrate scope of their method. This approach has led to innumerable and widely-used chemical reactions. However, it frequently provides methods that only work on model substrate-like compounds. Perhaps worse, reaction conditions that would enable the conversion of other substrates may be missed. We now show that a different approach, originally proposed by Kagan, in which a collection of structurally distinct substrates are evaluated in a single reaction vessel, can not only provide information on the substrate scope at a much earlier stage in methodology development, but even lead to a broadly applicable synthetic methodology. Using this multi-substrate screening approach, we have identified an efficient and stereoselective imidodiphosphorimidate organocatalyst for scalable Diels–Alder reactions of cyclopentadiene with different classes of α , β -unsaturated aldehydes. Investigation of a reaction scope usually starts with the optimization for a model substrate. Here, the authors apply a time-efficient multi-substrate screening approach to identify a general organocatalyst for the Diels–Alder reaction of cyclopentadiene with α , β -unsaturated aldehydes.