Construction of carbazole-based unnatural amino acid scaffolds via Pd(II)-catalyzed C(sp 3 )-H functionalization

• Published in: Organic & biomolecular chemistry 2022-06, Vol.20 (21), p.4391-4414
• Main Authors: Kaur, Ramandeep, Banga, Shefali, Babu, Srinivasarao Arulananda
• Format: Article
• Language: English
• Subjects: Aliphatic compounds; Amino acids; Aminoquinolines; Biological activity; Carbazole; Carbazoles; Catalysts; Functional materials; Norleucine; Phenylalanine; Phthalimide; Phthalimides; Stereochemistry; γ-Aminobutyric acid
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/d2ob00658h

We report the synthesis of carbazole-based unnatural α-amino acid and non-α-amino acid derivatives a Pd(II)-catalyzed bidentate directing group 8-aminoquinoline-aided β-C(sp )-H activation/functionalization method. Various -phthaloyl, DL-, L- and D-carboxamides derived from their corresponding α-amino acids, non-α-amino acids and aliphatic carboxamides were subjected to the β-C(sp )-H functionalization with 3-iodocarbazoles in the presence of a Pd(II) catalyst to afford the corresponding carbazole moiety installed unnatural amino acid derivatives and aliphatic carboxamides. Carbazole motif-containing racemic (DL) and enantiopure (L and D) amino acid derivatives including phenylalanine, norvaline, leucine, norleucine and 2-aminooctanoic acid with -stereochemistry and various non-α-amino acid derivatives including GABA have been synthesized. Removal of the 8-aminoquinoline directing group, deprotection of the phthalimide moiety and the preparation of carbazole amino acid derivatives containing free amino- and carboxylate groups are shown. The carbazole motif is prevalent in alkaloids and biologically active molecules and functional materials. Thus, this work on the synthesis of carbazole-based unnatural amino acid derivatives would enrich the libraries of unnatural amino acid derivatives and carbazoles.