Catalyst‐Free Site‐Selective Diverse Functionalization of Inherent C–H Bonds in 1‐Aryl‐β‐carbolines, Norharmane and Harmine

Abstract

A catalyst-free, site-selective diverse functionalization of latent CÀ H bonds in 1-aryl-β-carbolines and natural norharmane and harmine has been accomplished. This method enables the functionalization of 1-aryl-β-carbolines as C6-chlorination, C6bromination, and C4-nitration employing cost-effective, ecofriendly reagents such as trichloroisocyanuric acid (TCCA), Nbromosuccinimide (NBS) and tert-butyl nitrite (TBN), respectively. Pleasingly, these catalyst-/additive-free strategies were suitable with a broad range of substrate functionalities of different electronic nature, providing moderate to good yields of functionalized 1-aryl-β-carbolines. The critical/sensitive func-tionalities such as -CF 3 , -NO 2 , -CN, and 1-(thiophen-2-yl)-βcarboline were successfully employed, offering corresponding C6-halogenated or C4-nitrated products without strain. Furthermore, site-selective chlorination and bromination of two natural alkaloids such as harmine, norharmane were realized, resulting in corresponding halogenated products, including natural product eudistomin-N. In addition, we also employed these products in further diversification through -NO 2 reduction and Suzuki (CÀ C) coupling of brominated compounds to deliver a C6-arylated product.

Microwave-Assisted Ru(II)-Catalyzed Regioselective Methyl Acylation of 2-Arylbenzoazoles: Synthesis of Benzofuran Conjugates via C–H Activation/Annulation

“…C–H bond activation has emerged as a ubiquitous strategy in organic chemistry for the construction of C–C bonds or C–X (X = N, O, or S) bonds that are substantially significant. , In the past several decades, this approach has transcended conventional cross-coupling reactions, offering a platform for the development of novel molecular hybrids with wide applications in synthetic and pharmaceutical utility. This versatile protocol, underpinned by transition-metal catalysts, exemplifies an efficient, highly regioselective process . The site selectivity achieved by C–H functionalization can be attributed to the use of directing groups (DGs) that direct the incoming ligand toward the activated C–H bond. − Oxime ethers, amides, carboxylic acids, and pyridines are among the most commonly employed external directing groups in the realm of C–H bond activation. − However, it is noteworthy that the incorporation of these DGs often results in a deviation from the ideal step economy due to the additional steps required for their removal .…”