Palladium-Catalyzed Selective Carbonylation Reactions of Ortho-Phenylene Dihalides with Bifunctional N, O-Nucleophiles

Molecules. 2024 Nov 27;29(23):5620. doi: 10.3390/molecules29235620.

Abstract

Palladium-catalyzed carbonylation reactions of ortho-phenylene dihalides were studied using aminoethanols as heterobifunctional N,O-nucleophiles. The activity of aryl-iodide and -bromide as well as the chemoselective transformation of amine and hydroxyl functionalities were studied systematically under carbonylation conditions. Aminocarbonylation can be selectively realized under optimized conditions, enabling the formation of amide alcohols, and the challenging alkoxycarbonylation can also be proved feasible, enabling amide-ester production. Intramolecular double carbonylation reaction can be achieved using 1,2-diiodobenzene and amino alcohols featuring secondary amine groups, giving oxazocine derivatives. Useful reaction scope with various amino alcohols was performed with good isolated yields of the targeted compounds. Intramolecular C-O coupling of amide alcohols possessing bromo substituent in adjacent ortho position is also demonstrated as a potential next step in benzoxazepine heterocycle formation.

Keywords: amide alcohol; amide-ester; amino alcohol; aryl halide; bifunctional nucleophile; carbon monoxide; carbonylation; homogeneous catalysis; intramolecular carbonylation; palladium.

Grants and funding

The research was funded by NKFIH within the framework of the project TKP2021-EGA-17 and by the University of Pécs of project 014_2023_PTE_RK/10. This project was supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences. Supported by the ÚNKP-23-3-I-PTE-2127 New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund.