title: Pd-catalysed ligand-enabled carboxylate-directed highly regioselective arylation of aliphatic acids.
abstract: α-amino acids bearing aromatic side chains are important synthetic units in the synthesis of peptides and natural products. Although various β-C-H arylation methodologies for amino acid derivatives involving the assistance of directing groups have been extensively developed, syntheses that directly employ N-protected amino acids as starting materials remain rare. Herein, we report an N-acetylglycine-enabled Pd-catalysed carboxylate-directed β-C(sp3)-H arylation of aliphatic acids. In this way, various non-natural amino acids can be directly prepared from phthaloylalanine in one step in good to excellent yields. Furthermore, a series of aliphatic acids have been shown to be amenable to this transformation, affording β-arylated propionic acid derivatives in moderate to good yields. More importantly, this ligand-enabled direct β-C(sp3)-H arylation could be easily scaled-up to 10 g under reflux conditions, highlighting the potential utility of this synthetic method.
authors.affiliation: Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, China.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Chen
authors.affiliation: Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, China.
authors.forename: Chunchen
authors.initials: C
authors.lastname: Yuan
authors.affiliation: Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, China.
authors.forename: Guobao
authors.initials: G
authors.lastname: Li
authors.affiliation: Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, China.
authors.forename: Jingyu
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, China.
authors.forename: Yingsheng
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives / Q000378:metabolism*; D000596:Amino Acids / Q000378:metabolism*; D002244:Carbon / Q000378:metabolism; D002264:Carboxylic Acids / Q000378:metabolism*; D002384:Catalysis; D005227:Fatty Acids / Q000378:metabolism*; D005998:Glycine / Q000031:analogs & derivatives* / Q000378:metabolism; D006859:Hydrogen / Q000378:metabolism; D008024:Ligands; D010165:Palladium; D010455:Peptides / Q000138:chemical synthesis*
chemical_list: D000596:Amino Acids; D002264:Carboxylic Acids; D005227:Fatty Acids; D008024:Ligands; D010455:Peptides; D010165:Palladium; D002244:Carbon; D006859:Hydrogen; D000409:Alanine; D005998:Glycine; C006368:aceturic acid