Leveraging Pyrazolium Ylide Reactivity to Access Indolizine and 1,2‐Dihydropyrimidine Derivatives

• Published in: Chemistry : a European journal Vol. 30; no. 28; pp. e202400421 - n/a
• Main Authors: Tran, Ricky, Brownsey, Duncan K., O'Sullivan, Leonie, Brandow, Connor M. J., Chang, Emily S., Zhou, Wen, Patel, Ketul V., Gorobets, Evgueni, Derksen, Darren J.
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 17.05.2024; Wiley Subscription Services, Inc
• Subjects: 1,2-dihydropyrimidines; Alkynes; Catalysis; Catalysts; Chemistry; Chemistry, Multidisciplinary; heterocycle synthesis; High temperature; indolizines; Isocyanates; N-deletion; Physical Sciences; pyrazolium ylides; Salts; Science & Technology; Transition metals; indolizines; ANTIBACTERIAL; heterocycle synthesis; 1,2-dihydropyrimidines; pyrazolium ylides; N-deletion
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.202400421

N‐Heterocyclic ylides are important synthetic precursors to rapidly build molecular complexity. Pyrazolium ylides have largely been unexplored, and we demonstrate their diverse utility in this report. We show that these readily accessible building blocks can be used to construct different heterocyclic skeletons by varying the coupling partner. Indolizines can be formed via an N‐deletion type mechanism when reacting pyrazolium salts with electron deficient alkynes. 1,2‐Dihydropyrimidines can be formed via a rearrangement mechanism when reacting pyrazolium ylides with isocyanates. These reactions enable access to valuable heteroarenes without the need for transition metal catalysis, high temperatures, or strong bases. A mild, transition metal‐free method to synthesize indolizines and 1,2‐dihydropyrimidines from pyrazolium ylides is presented. The reaction of pyrazolium ylides with alkynes follows an N‐deletion mechanism to afford indolizines, while reaction with isocyanates follows a rearrangement into a 1,2‐dihydropyrimidine.