Transition Metal‐Catalyzed Regiodivergent C−H Arylations of Aryl‐Substituted Azoles

Abstract

The metal‐catalyzed direct functionalization of two different C−H bonds of the same organic molecule – also called regiodivergent C−H bond functionalization – is an important research topic in organic chemistry. Over the last decades, the number of tools to control such regiodivergent C−H bond functionalizations has increased significantly. One of the most effective tools consists of employing different metal sources as the catalysts. Palladium and copper catalysts are very effective to promote the direct arylation of 5‐membered ring heteroarenes, whereas the direct arylation using ruthenium and rhodium catalysts generally relies on the coordination of heteroelements to the metal. Therefore, in the presence of several aryl‐substituted azoles, the arylation of both the aryl unit using Ru‐ or Rh‐catalysis and of the azole unit using Pd‐ or Cu‐catalysts is possible. In this review, we will describe the scope and current limits of the use of this tool for the regiodivergent direct arylation of aryl‐substituted azoles.

Benzoxazole or Benzothiazole as an Innate Directing Group for Palladium- and Ruthenium-Catalyzed Complementary C–H Arylation: Functionalization of Biorelevant Heterocyclic Scaffolds

“…Frequently, in heterocyclic motifs, the Lewis basic sites are naturally present and can be harnessed as innate DGs. 18 An accurate site-selective C–H functionalization can be accomplished through a thermodynamically favored conformationally tight five- or six-membered metallacycle and has typically been exemplified at the ortho position via ortho C–H metalation. 11 19 The advantages of this approach include the following: (a) free from pre-functionalized insertion and post-functionalized cleavage of the directing unit, (b) practically more atom- and step-economic compared to preinstalled, traceless, and non-covalent interactive DGs, and (c) provide scope for diversified C–H functionalization of biorelevant heterocyclic scaffolds, leading to structure–activity relationship (SAR) studies assistive to lead identification in drug discovery programs.…”

Ligand‐assisted Palladium Catalyzed C5 Arylation Reaction of Imidazoles with Aryl Chlorides

“…[5][6] The direct CÀ H functionalization of imidazole have been reported. [7][8][9][10][11] Among of them, the regioselective CÀ H bond arylation of imidazole is an important protocol for the syntheses of imidazole derivatives. [12] Thus, recent advances in palladium-based complex catalyzed C5 arylation of imidazole were achieved by Doucet, [13] Lee, [14] Liu, [15] etc.…”

“…Recently, transition metal‐catalyzed C−H bond activation has emerged as an attractive alternative for molecular syntheses [5–6] . The direct C−H functionalization of imidazole have been reported [7–11] . Among of them, the regioselective C−H bond arylation of imidazole is an important protocol for the syntheses of imidazole derivatives [12] .…”