A DFT study on the formation of heterocycles via iodine(iii)-promoted ring expansion reactions

Author(s)

Lussari, Natalia ; Khan, Ajmir ; Pilli, Ronaldo A. ; Dos Santos, Alcindo A. ; Silva, Luiz F., Jr. ; Braga, Ataualpa A. C.

• Document type: Journal article
• Source: NEW JOURNAL OF CHEMISTRY; v. 46, n. 43, p. 11-pg., 2022-10-12.

Abstract

The ring expansion of bicyclic heterocycles bearing an exocyclic double bond promoted by Koser's reagent [hydroxy(tosyloxy)iodobenzene, HTIB] is a mild, practical, and metal-free methodology to access seven-membered rings containing fused furan, indole, pyrrole, and thiophene heterocycles providing an entry to structurally challenging bioactive natural products as well as pharmaceuticals. Here we describe our DFT results for the reaction conducted in aqueous methanol (95 : 5 v/v). These computational studies involving the microsolvation approach validated the regiochemistry of such kinetically favored rearrangements and helped to explain the faster reaction rate observed in aqueous methanol when compared to aqueous acetonitrile showcasing a fundamental role of protic solvents during the nucleophilic addition step which may support further experimental studies. (AU)

• FAPESP's process: 19/13104-5 - Planning and synthesis of inhibitors based on biological targets: the case of neglected kinases
• Grantee: Ronaldo Aloise Pilli
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/25770-6 - New frontiers in cross-coupling reactions promoted by palladium: combining enantioselective catalysis, C-H activations, new materials and in flux reactions aiming at high efficiency and sustainability in synthetic processes
• Grantee: Carlos Roque Duarte Correia
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 15/01491-3 - Theoretical study of cross-coupling reactions: homogeneous and heterogeneous catalysis
• Grantee: Ataualpa Albert Carmo Braga
• Support Opportunities: Regular Research Grants