Insights into the Friedel–Crafts Benzoylation of N-Methylpyrrole inside the Confined Space of the Self-Assembled Resorcinarene Capsule

• DOI: 10.1021/acs.orglett.3c01935
• Publication Date: 2023-08-29T07:51:24Z
• Authors: Veronica Iuliano; Carmen Talotta; Margherita De Rosa; Annunziata Soriente; Placido Neri; Antonio Rescifina; Giuseppe Floresta; Carmine Gaeta

Friedel-Crafts benzoylation of N-methylpyrrole 2 can run inside the confined space of the hexameric resorcinarene capsule C. The bridged water molecules at the corner of C act as H-bonding donor groups to polarize the C-Cl bond of benzoyl chlorides 3a-f. Confinement effects on the regiochemistry of the FC benzoylation of N-methylpyrrole are observed. The nature of the para-substituents of 3a-f and their ability to establish H-bonds with the water molecules of C work synergistically with the steric constrictions imposed by the capsule to drive the regiochemistry of products 4a-f. QM investigations indicate that inside the cavity of C, the FC benzoylation of 2 has a bimolecular concerted SN2 mechanism, appropriately, above-plane nucleophilic vinylic substitution (SNVπ)─supported by H-bonding interactions between water molecules and both the leaving Cl atom and the carbonyl group.