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

• Published in: Organic & biomolecular chemistry 2022-06, Vol.2 (21), p.4391-4414
• Main Authors: Kaur, Ramandeep, Banga, Shefali, Babu, Srinivasarao Arulananda
• Format: Article
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/d2ob00658h

We report the synthesis of carbazole-based unnatural -amino acid and non--amino acid derivatives via a Pd( ii )-catalyzed bidentate directing group 8-aminoquinoline-aided β-C(sp 3 )H activation/functionalization method. Various N -phthaloyl, dl -, l - and d -carboxamides derived from their corresponding -amino acids, non--amino acids and aliphatic carboxamides were subjected to the -C(sp 3 )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 anti -stereochemistry and various non--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. Synthesis of racemic and enantiopure carbazole-based unnatural amino acid motifs was accomplished via diastereoselective Pd( ii )-catalyzed β-C(sp 3 )H functionalization.