Increasing Catalyst Efficiency in C−H Activation Catalysis

Abstract

C-H activation reactions with high catalyst turnover numbers are still very rare in the literature and 10 mol % is a common catalyst loading in this field. We offer a representative overview of efficient C-H activation catalysis to highlight this neglected aspect of catalysis development and inspire future effort towards more efficient C-H activation. Examples ranging from palladium catalysis, Cp*Rh - and Cp*Co -catalysis, the C-H borylation and silylation to methane C-H activation are presented. In these reactions, up to tens of thousands of catalyst turnovers have been observed.

Rhodium‐Catalysed [4+2] Annulation of Aromatic Oximes with Terminal Alkenes by C−H/N−O Functionalization towards 3,4‐Dihydroisoquinolines

“…[1] Accordingly, considerable effort has been devoted to developing increasingly efficient methods for the construction of such isoquinoline molecular scaffolds, especially through intramolecular cyclization or intermolecular annulation reactions. [4] In recent years, transition-metalcatalysed intermolecular annulation of aromatic oximes and their derivatives (often esters) with unsaturated hydrocarbons (e. g., alkynes, allenes, alkenes, ketenes) have proved to be promising platforms for the preparation of nitrogen-containing heterocycles, wherein the N À O bond in aromatic oximes serves as the internal oxidative chelation group to selectively achieve ortho-C(sp 2 )À H functionalization. [4] In recent years, transition-metalcatalysed intermolecular annulation of aromatic oximes and their derivatives (often esters) with unsaturated hydrocarbons (e. g., alkynes, allenes, alkenes, ketenes) have proved to be promising platforms for the preparation of nitrogen-containing heterocycles, wherein the N À O bond in aromatic oximes serves as the internal oxidative chelation group to selectively achieve ortho-C(sp 2 )À H functionalization.…”

“…[2,3] Despite substantial progress in the field, the development of highly atom-economic, sustainable routes that can achieve CÀ H functionalization under external-oxidizing-reagent-free conditions that release nontoxic waste products (e. g., H 2 O) remains a challenging area. [3][4][5][6] While the annulation of aromatic oximes with internal alkynes has been thoroughly investigated for the preparation of 3,4-disubstituted isoquinolines (Scheme 1a-i), [3,5] similar versions with alkenes are rare. [3][4][5][6] While the annulation of aromatic oximes with internal alkynes has been thoroughly investigated for the preparation of 3,4-disubstituted isoquinolines (Scheme 1a-i), [3,5] similar versions with alkenes are rare.…”

“…[2,3] Despite substantial progress in the field, the development of highly atom-economic, sustainable routes that can achieve CÀ H functionalization under external-oxidizing-reagent-free conditions that release nontoxic waste products (e. g., H 2 O) remains a challenging area. [4] In recent years, transition-metalcatalysed intermolecular annulation of aromatic oximes and their derivatives (often esters) with unsaturated hydrocarbons (e. g., alkynes, allenes, alkenes, ketenes) have proved to be promising platforms for the preparation of nitrogen-containing heterocycles, wherein the N À O bond in aromatic oximes serves as the internal oxidative chelation group to selectively achieve ortho-C(sp 2 )À H functionalization. [3][4][5][6] While the annulation of aromatic oximes with internal alkynes has been thoroughly investigated for the preparation of 3,4-disubstituted isoquinolines (Scheme 1a-i), [3,5] similar versions with alkenes are rare.…”

“…[4] In recent years, transition-metalcatalysed intermolecular annulation of aromatic oximes and their derivatives (often esters) with unsaturated hydrocarbons (e. g., alkynes, allenes, alkenes, ketenes) have proved to be promising platforms for the preparation of nitrogen-containing heterocycles, wherein the N À O bond in aromatic oximes serves as the internal oxidative chelation group to selectively achieve ortho-C(sp 2 )À H functionalization. [3][4][5][6] While the annulation of aromatic oximes with internal alkynes has been thoroughly investigated for the preparation of 3,4-disubstituted isoquinolines (Scheme 1a-i), [3,5] similar versions with alkenes are rare. [6] Moreover, these transformations focus on special alkenes, including vinyl acetates, [6a] 1,3-dienes [6b] and electron-poor alkenes, [6c] which serve as convenient acetylene equivalents for the synthesis of 3-substituted isoquinolines.…”

C−H Alkenylation of Pyrroles by Electronically Matching Ligand Control

“…Transition-metal-catalyzed CÀHf unctionalization reactions of heteroarenes have emergeda mong the most atom-a nd stepeconomicala pproaches for the preparationo fe lectronically and sterically varied heteroarenes for materials science and drug discovery. [1,2] Pyrroles are important targets forC ÀHf unctionalization because of their prevalence in polymers, dyes, and drugs,i ncluding atorvastatin, ketorolac, andt olmetin. [3] The instability of most halopyrroles and high cost when available make the direct functionalization of pyrroles much more attractive than traditional cross-coupling reactions of the prefunctionalized congeners.…”