Construction of Diarylmethane‐ and Triarylmethane‐Based Unnatural Amino Acid Motifs via Pd(II)‐Catalyzed Diastereoselective sp 3 C–H Arylation

This paper reports the incorporation of diarylmethane (DAM) and triarylmethane (TAM) moieties in the backbone of amino acid molecules via directing group‐aided site‐selective sp 3 C–H functionalization. In general, DAM and TAM are found in numerous natural products, bioactive compounds, agrochemicals, and material chemistry. Given the importance of DAM and TAM molecules, this work reports the expansion of the library of DAM‐ and TAM‐based unnatural amino acid motifs. N ‐Phthaloyl carboxamides of amino acids possessing 8‐aminoquinoline directing group were subjected to the Pd(II)‐catalyzed β ‐C(sp 3 )–H activation and arylation using DAM‐ and TAM‐based iodoaryls as the coupling partners. This process has led to the synthesis of novel DAM‐ and TAM‐based unnatural amino acid motifs, including phenylalanine, norvaline, norleucine, leucine, 2‐aminobutyric acid, and alanine. Then, synthetic transformations, including the removal of the directing and the phthalimide protecting groups, and the synthesis of free amino group‐containing DAM‐ and TAM‐incorporated amino acid motifs, were shown. Examples of peptide compounds containing the DAM or TAM moiety and unnatural amino acid derivatives were synthesized. Furthermore, we have presented preliminary studies on the metal‐sensing properties of representative DAM and TAM molecules synthesized in this work.