Rapid access to diverse α-carbolines through sequential transition metal catalyzed amination and direct C–H arylation

Mild and Efficient Synthesis of Functionalized Carbazoles via a DBU‐Assisted Sequence Involving Cu‐ and Pd‐Catalyzed Coupling Reactions

“…Before examining the scope of this C−H arylation with other substrates 3 described above, we wished to compare the efficiency of the optimal conditions thus identified (Table , entry 11) in the case of 2‐bromo‐ N ‐phenylaniline ( 3a′ ), the bromo analogue of 3 a . Starting from 3a′ , carbazole 4 a was isolated only in 5% yield; slight yield improvement (14%) was observed when 2‐(dicyclohexylphosphino)biphenyl (CyJohnPhos, 10 mol%) was used as a ligand (Table , entries 20–21); higher conversion and yield (72%) were observed when DMA was substituted to toluene, and the reaction mixture heated at 130 °C (entry 22); the conditions employed by Mineno et al . for the synthesis of α‐carbolines.…”

Applications of Palladium-Catalyzed C–N Cross-Coupling Reactions

“…As previously shown in Scheme 26 b, α-carbolines (pyrido[2,3- b ]indoles) can be accessed by coupling anilines and 2,3-dichloropyridines. In a complementary approach, α-carbolines were also prepared from 3-bromo-2-aminopyridines and aryl iodides, first by Sakamoto and co-workers 211 and more recently by the group of Mineno and Mizufune (Takeda) 212 ( Scheme 61 a). Both α-carboline syntheses required different catalysts for each coupling step, as opposed to the one-pot protocols for carbazole preparation ( Scheme 26 , section 3.1.1 ).…”

“…Mineno, Mizufune, and their co-workers (Takeda) applied their α-carboline synthesis protocol 212 to access aurora B kinase inhibitor 304 , a candidate for cancer therapy ( Scheme 64 ). 221 The construction of the α-carboline core in the medicinal chemistry route was achieved via intermolecular Ullmann coupling, followed by intramolecular S N Ar.…”

Discovery of a novel allosteric inhibitor scaffold for polyadenosine-diphosphate-ribose polymerase 14 (PARP14) macrodomain 2

“…8-Aza analogue 43 was obtained by a series of three consecutive Pd-catalyzed coupling reactions. 22 Chemoselective Buchwald-Hartwig amination of 1-bromo-2-iodobenzene with 2-amino-3-bromopyridine 40 using XantPhos as a ligand gave phenylaminopyridine 41 , which was cyclised to 8-bromo-α-carboline 42 using CyJohnPhos in an intramolecular Heck coupling. Finally, the acetylaminophenyl residue was introduced in a standard Suzuki-Miyaura cross-coupling ( Scheme 4 ).…”