Palladium catalyzed chloroethoxylation of aromatic and heteroaromatic chlorides: an orthogonal functionalization of a chloroethoxy linker

• Published in: Organic & biomolecular chemistry Vol. 16; no. 26; pp. 4895 - 4899
• Main Authors: Petho, Balint, Vangel, Dora, Csenki, Janos T., Zwillinger, Marton, Novak, Zoltan
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 2018; Royal Society of Chemistry
• Subjects: Aromatic compounds; Chemistry; Chemistry, Organic; Chlorides; Coupling (molecular); Cross coupling; Ethers; Intermediates; Molecular chains; Organic chemistry; Palladium; Physical Sciences; Science & Technology; Sodium; IODIDES; CROSS-COUPLING REACTIONS; ETHERS; C-O BOND; ARYL HALIDES; ARYLATION; CHEMISTRY; REDUCTIVE ELIMINATION; PRIMARY ALCOHOLS; TRIFLUOROMETHYLATION
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c8ob01146j

A novel disconnection based on cross-coupling chemistry was designed to access pharmaceutically relevant aryl-aminoethyl ethers. The developed palladium-catalyzed functionalization of aryl-and heteroaryl chlorides with a sodium tetrakis-(2-chloroethoxy) borate salt is orthogonal to the simple nucleophilic replacement of the chloro function of the ethylene linker. The transformation enables efficient 2-chloroethoxylation in the absence of an additional external base. Subsequent amine substitution of the alkyl halide affords 2-aminoethoxy arenes. The applicability of this method was demonstrated through the synthesis of various aryl-and heteroaryl-alkyl ethers, including the intermediates of marketed drug molecules.