Synthesis of Cyclophane-Braced Peptide Macrocycles via Palladium-Catalyzed Intramolecular C(sp<sup>3</sup>)–H Arylation of <i>N</i>-Methyl Alanine at C-Termini
Xinghua Li, Liping Qi, Bo Li, Zhenxiang Zhao, Gang He, Gong Chen
Abstract
A method for the construction of cyclophane-braced peptide macrocycles via Pd-catalyzed aminoquinoline-directed intramolecular C(sp3)–H arylation with aryl iodides is developed. Unlike our previous AQ-directed exo-type intramolecular C–H arylation of long alkyl tails, this endo-type C–H cyclization reaction takes places on the β-methyl group of N-methyl alanine at the C-termini of peptides. Unusual C–N cleavage side products of Ala were observed and attributed to intramolecular deprotonation-assisted α,β-elimination of the palladacycle intermediate.
Topics & Concepts
ChemistryIntramolecular forceCyclophaneStereochemistryArylDeprotonationPalladiumAlkylPeptideCatalysisCleavage (geology)AlanineMedicinal chemistryMoleculeOrganic chemistryAmino acidIonFracture (geology)EngineeringBiochemistryGeotechnical engineeringCatalytic C–H Functionalization MethodsChemical Synthesis and AnalysisRadical Photochemical Reactions