Palladium Catalyzed Regioselective C4‐Arylation and Olefination of Indoles and Azaindoles

Abstract

A convergent strategy for the synthesis of biologically relevant C4-substituted indole scaffolds was demonstrated using Pd(II)-catalyzed remote CÀH functionalization of indoles and azaindoles. The reaction displays high regioselectivity for the C4-position of indole-3-carbaldehydes using glycine as an inexpensive transient directing group. Notable features of this transformation include the selective formation of six-membered palladacyle and excellent functional group tolerance.

Transient imine directing groups for the C–H functionalisation of aldehydes, ketones and amines: an update 2018–2020

“…In 2019, Maiti and Volla published a method to arylate indole carboxaldehydes selectively at the γ-position, extending the scope of the method to include aza-indoles (Scheme 9). 33 While the benzyl protecting group was most effective, unprotected indole could also be arylated, albeit in lower yield. Indoles bearing aryl groups and halides at C6 all reacted in good to excellent yields.…”

Recent Advances in Metal‐catalyzed Alkylation, Alkenylation and Alkynylation of Indole/indoline Benzenoid Nucleus

“…Later, Volla group showed a Pd(II)‐catalyzed direct C4‐alkenylation of indoles with iodo‐acrylates using a transient‐DG (Scheme 16). [19] Glycine is used as the transient auxiliary to assist the C4‐alkenyaltion of 3‐formylindoles exclusively. The reaction proceeds via the initial in‐situ imine formation by condensation of glycine with 3‐formylindoles.…”

Application of Conjugated Carbonyls in the Synthesis of Heterocycles via Oxidative Cycloaddition and Cyclization Reactions

“…Imidazo [1,2-a]triazines show a wide range of biological activities like anti-inflammatory, antiviral, antibacterial, antitumor activity etc. [32] Cui et al in 2017 developed a Cu-catalyzed oxidative cyclization between 2-amino-1,3,5-triazines and chalcone derivatives for the synthesis of aroylimidazo [1,2-a] [1,3,5] triazines (Scheme 29). [33] The combination of CuCl 2 (20 mol%) and I 2 (2 equiv.)…”

“…in chlorobenzene under oxygen atmosphere afforded the fused imidazole derivatives. Various 2-amino-1,3,5-triazines and chalcones were susceptible under the optimized reaction conditions and produced the corresponding aroylimidazo [1,2-a] [1,3,5]triazines with high to excellent yields. The methodology was also applicable for the gramscale synthesis of the product.…”

“…[3,4] Among these, CÀ H functionalization has gained much attraction due to its usefulness in the direct synthesis of drug-like molecules from the readily available/accessible reactants. [5] It offers a straightforward synthesis of cyclic organic molecules in a time-and step-economic pathway as no prefunctionalization of the reactant is required. As a result, CÀ H functionalization has been widely used for the synthesis of various biologically and pharmaceutically active heterocycles.…”