Construction of β‐Phenylalanine Derivatives through Pd‐Catalyzed, C(sp2)−H (ortho) Functionalization

Abstract

AbstractThis paper describes the Pd(II)‐catalyzed, picolinamide‐directing‐group‐aided C(sp2)−H (ortho) functionalization of racemic and enantiopure β‐phenylalanines and 3‐amino‐3‐phenylpropanols (1,3‐amino alcohols). The C(sp2)−H (ortho) functionalizations including arylation, bromination, iodination, and alkoxylation were attempted. The C(sp2)−H (ortho) arylation reactions gave biaryl or terphenyl‐type β‐phenylalanine scaffolds, halogenation and methoxylation reactions gave ortho C−H halogenated or methoxylated β‐phenylalanines. Additionally, the C−H arylation of an ortho‐methyl substituted β‐phenylalanine containing both C(sp2)−H and remote C(sp3)−H bonds was investigated. β‐Phenylalanine is an arylated β‐amino acid motif present in various natural products, bioactive molecules, and β‐peptides and it is a precursor to medicinally active compounds. Accordingly, this work contributes to the expansion of the library of unnatural β‐phenylalanine (β‐amino acid) derivatives through site‐selective C−H functionalization.