Unlocking regioselective meta-alkylation with epoxides and oxetanes via dynamic kinetic catalyst control

• Published in: Nature communications Vol. 15; no. 1; pp. 31 - 9
• Main Authors: Bai, Peng-Bo, Durie, Alastair, Wang, Gang-Wei, Larrosa, Igor
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02.01.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 140/131; 140/58; 639/638/403/933; 639/638/403/934; 639/638/77/888; Acids; Alkylating agents; Alkylation; Aromatic compounds; Catalysis; Catalysts; Epoxides; Humanities and Social Sciences; Hydrogen bonds; Lead; multidisciplinary; Reagents; Regioselectivity; Ring opening; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-44219-6

Regioselective arene C−H bond alkylation is a powerful tool in synthetic chemistry, yet subject to many challenges. Herein, we report the meta -C−H bond alkylation of aromatics bearing N -directing groups using (hetero)aromatic epoxides as alkylating agents. This method results in complete regioselectivity on both the arene as well as the epoxide coupling partners, cleaving exclusively the benzylic C−O bond. Oxetanes, which are normally unreactive, also participate as alkylating reagents under the reaction conditions. Our mechanistic studies reveal an unexpected reversible epoxide ring opening process undergoing catalyst-controlled regioselection, as key for the observed high regioselectivities. Regioselective arene C−H bond alkylation is a powerful tool in synthetic chemistry, yet subject to many challenges. Here, the authors report the meta-C−H bond alkylation of aromatics bearing N-directing groups using (hetero)aromatic epoxides as alkylating agents.