oxidation by bioinspired catalysis. Selective C–H oxidation is a routine task in biological system. The selectivity in enzymatic process is governed by the virtue of several interactions that enable the proper substrate trajectory and geometric orientation. Imitating such reactivity in laboratory synthesis is relatively challenging yet worthy to explore. Therefore, a persistent attempt to comprehend the mechanistic insight of biological reactivity and catalyst or ligand design was pronounced to furnish site selective functionalization of aliphatic substrate. A comprehensive survey on aliphatic C–H oxidation imparted by the bio‐inspired catalysis is outlined by Costas in Chapter 13.
The endless curiosities of human mind are the key to the technological advancements and evolution. This eternal truth has remained the essence for every piece of advancement since ancient times and will continue to remain persistent till times eternity. Modernization of scientific research in organic chemistry genre has shaped up in the form of C–H activation based protocols that has fostered a novel dimension in synthetic prospects and restructured the temperament of the scientific fraternity accordingly. This book besides providing a comprehensive scenario on the field of distal C–H activation also aims to inculcate cognizance among researchers of present and future generations to streamline and channelize their scientific understanding for the welfare of human civilization.
2 Transition Metal‐Catalyzed Remote meta‐C–H Functionalization of Arenes Assisted by meta‐Directing Templates
Yuzhen Gaoand Gang Li
State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences (CAS), 155 West Yang‐Qiao Road, Fuzhou, Fujian, 350002, China
2.1 Introduction
Site‐selective C–H functionalization has emerged as an important synthetic methodology in organic synthesis in the past two decades [1–10]. For such synthetic methodology to be synthetically useful, precise control of the site‐selectivity of C–H functionalization reactions is one of the most important issues required to be resolved due to the presence of several C
ortho‐C–H functionalization has been usually promoted by σ‐chelation of the directing template. However, applying this chelation to meta‐C–H functionalization is much more challenging since a strained cyclophane‐like metallacycle might be involved in this transformation [11]. In 2012, the group of Yu and coworkers disclosed the first geometry‐induced remote meta‐C–H activation of toluenes and hydrocinnamic acids with a Pd(II) catalyst, which is assisted by two types of rationally designed nitrile‐based templates that are covalently linked with toluenes or hydrocinnamic acids through an ether or amide bond (Scheme 2.1b) [11]. The presumable linear coordination mode of the nitrile‐based chelating functionality (CF) in the U‐shaped template that weakly coordinates to the palladium center in an end‐on fashion is important for securing a possible less strained cyclophane‐like pre‐transition state. However, a more likely catalytic scenario is the weakly chelating template may “catch and release” the Pd(II) catalyst closely to the target meta‐C
Scheme 2.1 Directing template assisted meta‐C
(a) Li et al. [5], Yang [6], Chattopadhyay and Bisht [7], Dey et al. [8], Ghosh and De Sarkar [9], and Dey et al. [10]; Source: (b) Modified from Leow et al. [11].
Inspired by this pioneering work, a series of directing template assisted remote meta‐C–H activation reactions have been realized for a list of substrates including acids, amines, sulfonic acids, and so on (Scheme 2.1c). Notably, one of the key features of these reactions is the target C
Herein, we summarize important achievements that were disclosed until October 2019 in the field of directing template assisted meta‐C–H functionalization of arenes with Pd or Rh catalysts since 2012. Different aspects of this type of methodology will be covered while discussing the works that are categorized by the substrate type. Important mechanistic studies on this methodology will also be included. It is hoped that the reader will learn the key points, especially structural features, for rationally designing a feasible template for new substrates as well as developing new types of meta‐C–H transformation after reading this chapter.
Scheme 2.2 Three categories of chelating functionality (CF). (a) N‐Based CN‐containing CF; (b) N‐based heteroarene‐containing CF; (c) O‐based CO2H‐containing CF.
2.2 Template‐Assisted
