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

GEROSA, GABRIELA; OUYANG, JIE; FARÈS, CHRISTOPHE; KIM, HYEJIN; KASAPLAR, PINAR; GUERRY, PAUL; ARONOW, JONAS; LINGNAU, JULIA B.; LIST, BENJAMIN

NATURE COMMUNICATIONS

Springer Nature

Lugar: New York; Año: 2019 vol. 10

2041-1723

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.