Amine‐Directed Palladium‐Catalyzed C−H Halogenation of Phenylalanine Derivatives

Abstract

An efficient primary-amine-directed, palladiumcatalyzed CÀ H halogenation (X = I, Br, Cl) of phenylalanine derivatives is reported on a range of quaternary amino acid (AA) derivatives thanks to suitable conditions employing trifluoroacetic acid as additive. The extension of this original native functionality-directed ortho-selective halogenation was even demonstrated with the more challenging native phenylalanine as tertiary AA.

Mixed N‐heterocyclic carbene and benzyl‐, phenethyl‐, and biphenylamine coordinated Pd complexes: Anticancer activities and stereo‐electronic effects

“…15 This reaction sequence somewhat corroborated the catalytic mechanism of ortho-bromination of aryl-amines with palladium catalysts. 16 Monodentate complex 7 could undergo similar deprotonation with AgOAc to afford the target bidentate complex 8 (Scheme 1, path C).…”

Native Amine-Directed ortho-C–H Halogenation and Acetoxylation /Condensation of Benzylamines

“…While we had been unable to cleanly isolate dichlorination products of unfunctionalized benzylamines, clean 2,6-dibrominated products could be isolated, albeit with only moderate selectivity for dibrominated (2l) to monobrominated (2m) products. 22 Increased loading of NBS led to decreased yields and more complex product mixtures. Inspired by the work of Yu, we next targeted the C-H fluorination of free benzylamine substrates.…”

Native Amino Group Directed Site-Selective ε-C(sp2)–H Iodination of Primary Amines

“…Ortho-selective iodination of free primary amines was only reported by Briere's team. 9 They realized the selective ortho-iodination of 2-amino-2-phenylacetate and phenylalaninate (Scheme 1b). So far, there is a high demand for developing a new method for the ortho-selective C−H activation of unmodified 3-arylpropan-1-amines.…”

“…This reaction process involved a seven-membered palladacycle that is less kinetically favorable than five- or six-membered palladacycles and required a directing group for the ε-C­(sp 2 )–H activation step. Ortho -selective iodination of free primary amines was only reported by Briere’s team . They realized the selective ortho -iodination of 2-amino-2-phenylacetate and phenylalaninate (Scheme b).…”