Construction of β ‐Phenylalanine Derivatives through Pd‐Catalyzed, C(sp 2 )−H ( ortho ) Functionalization

Abstract This paper describes the Pd(II)‐catalyzed, picolinamide‐directing‐group‐aided C(sp 2 )−H ( ortho ) functionalization of racemic and enantiopure β ‐phenylalanines and 3‐amino‐3‐phenylpropanols (1,3‐amino alcohols). The C(sp 2 )−H ( ortho ) functionalizations including arylation, bromination, iodination, and alkoxylation were attempted. The C(sp 2 )−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(sp 2 )−H and remote C(sp 3 )−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.