The ability to mimic the activity of natural enzymes using supramolecular constructs (artificial enzymes) is a vibrant scientific research field. Herein, we demonstrate that cucurbit[7]uril (CB[7]) can catalyse Diels–Alder reactions for a number of substituted and unreactive N-allyl-2-furfurylamines under biomimetic conditions, without the need for protecting groups, yielding powerful synthons in previously unreported mild conditions. CB[7] rearranges the substrate in a highly reactive conformation and shields it from the aqueous environment, thereby mimicking the mode of action of a natural Diels–Alderase. These findings can be directly applied to the phenomenon of product inhibition observed in natural Diels–Alderase enzymes, and pave the way toward the development of novel, supramolecular-based green catalysts.O.A.S. and A.P. acknowledge an ERC starting investigator grant (ASPiRe 240629) and EPSRC Programme Grant (NOtCH, EP/L027151/1) for the support, G.W. thanks the Leverhulme Trust (Natural material innovation for sustainable living) for the support, S.J.B. thanks the European Commission for a Marie Curie Fellowship (NANOSPHERE, 658360), E.R. gratefully acknowledges financial support from EPSRC (EP/N020669/1), E.M. and X.L. acknowledge the American Chemical Society Petroleum Research Fund (PRF No. 51053-ND4), the Department of Chemistry and Biochemistry, the College of Arts and Sciences and the Vice President for Research at Ohio University
