Effective Tools for the Metal‐Catalyzed Regiodivergent Direct Arylations of (Hetero)arenes

Abstract

The direct functionalization of two different C−H bonds of the same organic molecule using different procedures ‐ also called regiodivergent C−H bond functionalization ‐ currently represents an important research topic in organic chemistry, as it demonstrates the versatility of C−H bond functionalization methodology. Over the last decade, the number of tools to control such regiodivergent C−H bond functionalizations has increased significantly. In this account, we will present the various tools that allowed us to arylate different positions of various (hetero)arenes, via a C−H bond functionalization, using palladium or ruthenium catalysis.

Palladium-catalysed C–H arylation of benzophospholes with aryl halides

“…Particularly notable is the successful application of 5-bromoindole, 5-bromobenzofuran, and 5-bromobenzothiophene that bear potentially reactive C2/C3–H bonds under the C–H activation conditions. 10 The phosphole C2–H showed higher reactivity, and the corresponding arylated benzophospholes ( 4an–ap ) were dominantly generated under the standard conditions. Additionally, our direct C–H arylation protocol was applicable in the reaction with 2-bromothiophenes to form the phosphole–thiophene linkages ( 4aq and 4ar ), albeit in moderate yields.…”

“…9 Among them, the direct C–H arylation of benzoheteroles such as indoles, benzothiophenes, and benzofurans, to construct functional aryl-heteroaryl linkages has received tremendous attention and has made remarkable progress (Scheme 2a, left). 10 However, the direct catalytic C–H transformation of phosphorus analogues has not been successful so far, and only a formal C–H arylation of P -aryl phospholes was recently reported under Cu catalysis. 11 Given the significant optical performance of C2- and C3-diarylated benzophospholes, 1–3 the development of C–H arylation strategy can provide a potentially more practical alternative for the rapid construction of benzophosphole-based π-electron materials (Scheme 2a, right).…”

Palladium-catalyzed direct C5-arylation or C4,C5-diarylation of 2-alkylisothiazol-3-ones

“…2 This methodology has been applied to a wide range of 5-membered ring heteroaromatics such as pyrroles, indoles or thiophenes to access (hetero)biaryls using in many cases sustainable reaction conditions. [3][4][5] When this "direct arylation" methodology can be used for the late-stage functionalization of bioactive compounds, it provides a very appealing tool for a fast screening of the biological properties of a family of compounds containing a specific unit.…”

Transition-Metal-Catalyzed Divergent C–H Functionalization of Five-Membered Heteroarenes

“…Hence, the parent forms of these heterocycles are more readily available and cheaper than the substituted forms, making the direct use of the parent rings more attractive. Therefore, C–H functionalization of five-membered heteroarenes has been mostly performed by nondirected approaches, where catalysts, ligands, solvents, and additives are carefully selected to match with the electronic and steric properties of the heteroaryl C–H bonds. , Significant advances have been made in C–H arylation − and annulation , reactions using aryl group donors, which are often performed in a divergent manner. In addition, various methods have been developed for the direct installation of alkynyl, alkenyl, and alkyl groups at the most reactive site of five-membered rings.…”