Ligand‐Enabled Arylation of γ‐C−H Bonds

Abstract

Pd(II)-catalyzed arylation of γ-C(sp3)–H bond of aliphatic acid-derived amides is developed by using quinoline-based ligands. Various γ-aryl-α-amino acids are prepared from natural amino acids using this method. The influence of ligand structure on reactivity is also systematically investigated.

Site‐Selective C–H Bond Activation/Functionalization of Alpha‐Amino Acids and Peptide‐Like Derivatives

“…Similar to the previously described β‐arylation protocol, a ligand‐enabled methodology for the γ‐arylation of valine derivatives 96 was reported using a quinoline‐based ligand L8 (Scheme ) . A broad range of common functional groups on the iodoarene were tolerated.…”

Ligand‐Enabled β‐C–H Arylation of α‐Amino Acids Without Installing Exogenous Directing Groups

“…We suspect this is due to the Thorpe-Ingold Effect which favors cyclopalladation. [14] It is worth noting that this chemistry is applicable to α -quaternary acid substrates: Gemfibrozil ( 3h ), an oral drug used to lower lipid levels, [15] was arylated in good yields (72%); in the absence of ligand, 4h was only obtained in 30% yield. We attempted to expand the substrate scope to other carboxylic acids, however the yields were generally low (see Table S4 in supporting information).…”

Directed γ-C(sp3)–H Alkylation of Carboxylic Acid Derivatives through Visible Light Photoredox Catalysis

“…A literature survey disclosed two strategies for addressing this issue. First, Corey, 5 Chatani, 6 Chen 7 and Yu 8 pioneered primary γ-C-H arylation, alkynylation, olefination and intramolecular amination reactions based on sterically controlled formations of six-membered metallacycles (Fig 1a). Methylene and methine groups are not amenable to these reactions.…”