Accessing Remote meta‐ and para‐C(sp²)−H Bonds with Covalently Attached Directing Groups

Abstract

Directing group assisted ortho‐C−H activation has been known for the last few decades. In contrast, extending the same approach to achieve activation of the distal meta‐ and para‐C−H bonds in aromatic molecules remained elusive for a long time. The main challenge is the conception of a macrocyclic transition state, which is needed to anchor the metal catalyst close to the target bond. Judicious modification of the chain length, the tether linkage, and the nature of the catalyst‐coordinating donor atom has led to a number of successful studies in the last few years. This Review compiles the significant achievements made in this field of both meta‐ and para‐selectivity using covalently attached directing groups, which are systematically classified on the basis of their mode of covalent attachment to the substrate as well as their chemical nature. This Review aims to create a more heuristic approach for recognizing the suitability of the directing groups for use in future organic transformations.

Diaryliodoniums Salts as Coupling Partners for Transition-Metal Catalyzed C- and N-Arylation of Heteroarenes

“…Very recently, Kumar and co-workers reported a site-selective palladium-catalyzed CH arylation of quinolin-4(1H)-ones using diaryliodonium Salts [81]. Driven by the design of substrate-controlled site-selective reactions, the authors described an elegant C3-, C5-and C8-selective arylation by the utilization of an intrinsic directing group (Scheme 15a) [82,83]. The regioselective keto-directed C5 arylation of quinolin-4(1H)-one was conducted using 5 mol% Pd(OAc) 2 as a catalyst in AcOH at 100 • C for 6 h and various unsymmetrical aryl-(mesityl) iodonium triflates, leading to a wide range of 5-arylquinolin-4(1H)-ones in high yields (Scheme 15b).…”

Palladium‐Catalyzed Directed meta‐Selective C−H Allylation of Arenes: Unactivated Internal Olefins as Allyl Surrogates

“…Over the past years, our group has focused on these developments in terms of designing new directing groups, introducing new functionalities, and understanding the reaction mechanisms . The use of a nitrile DG for meta ‐C−H functionalization confines the method to the introduction of less‐reactive coupling partners because of the weak coordination and side‐on binding of the nitrile . In 2017, we introduced a stronger coordinating pyrimidine‐based DG, which was more efficacious than the nitrile DG, for the introduction of different functionalities …”

Coordination Assisted Distal C−H Alkylation of Fused Heterocycles

“…In this context the directing group (DG) approach has become prevalent among chemists in order to achieve selective C−H functionalization at both aromatic as well as aliphatic systems . Over the time, evolution of directing groups led to selective activation at distal position of arene and aliphatic systems . However, this approach consistently demands installation and removal of directing group pre‐ and post‐functionalization, respectively.…”