Versatile synthesis of functionalized β- and γ-carbolines via Pd-catalyzed C–H addition to nitriles/cyclization sequences

Abstract

The first example of versatile synthesis of functionalized β-carbolines and γ-carbolines via redox-free Pd-catalyzed C-H addition of indole to nitrile/cyclization sequences is reported. A wide range of functionalized β-carbolines and γ-carbolines can be prepared from readily accessible indoles and nitriles in good to excellent yields under the optimal conditions.

Synthesis Strategies for α‐, β‐, γ‐ and δ‐Carbolines

“…Similarly, biphenyl compound 107 was also generated by Suzuki‐Miyagi coupling, which was cyclized with aniline through further Buchwald‐Hartwiger reaction under the catalysis of palladium ligands to give the target β‐carboline 108 (Scheme 17B) [49] . Moreover, one‐pot addition‐cyclization of nitrile 109 to substituted indole 110 was also developed to synthesize β‐carboline 111 in the presence of Pd(OAc) 2 catalyst (Scheme 17C) [50] …”

Application of Transition Metal‐Catalyzed C−H Activation Strategies in the Synthesis and Functionalization of β‐Carbolines

“…The sequential mechanism at first implies oxidative addition of aryl iodide (6) Similarly, annulation with nitrile was explored by Liao and his group in 2018. [56] Nitriles are used as a common platform in the chemical industries due to their low cost and versatile transformations. This report was the first and foremost example of a multifaceted synthesis of functionalized β-carbolines (10) via intermolecular CÀ H addition of 3-substituted indole (8) with nitrile (9) and cyclization cascade using a catalytic amount of Pd(II) with 2,2'-bipyridine in THF/acetic acid (3 : 1) system at 120°C (Scheme 5).…”

“…Similarly, annulation with nitrile was explored by Liao and his group in 2018 [56] . Nitriles are used as a common platform in the chemical industries due to their low cost and versatile transformations.…”

Synthesis of 1-Indolyl-3,5,8-Substituted γ-Carbolines: One Pot Metal-Solvent Free Protocol and Biological Evaluation

“…Much later, Larock and co-workers developed Pd/Cu catalyzed imino-annulation of internal alkynes, 15 which paved the way for transition-metal catalysed cyclization as an easy access to these scaffolds. Notably, gold catalysed tandem cycloisomerization/Pictet−Spengler cyclisation of 2-(4-aminobut-1-yn-1yl)aniline, 16 Ru and Rh catalysed [2+2+2] cycloadditions of yne-ynamides, 17 and Pdcatalysed tandem coupling-cyclisation 18 are significant works in the area. However, the use of toxic and expensive metal catalysts has limited their development as environment friendly synthetic protocols.…”