An Introductory Overview of C–H Bond Activation/ Functionalization Chemistry with Focus on Catalytic C(sp3)–H Bond Borylation

Abstract

The direct and selective functionalization of C–H bonds provides novel disconnections and innovative strategies to streamline the synthesis of molecules with diverse complexities. However, despite the significant advances in the elaboration of techniques for C–H activation, the utilization of unactivated C(sp3)–H bonds remains challenging. In particular, asymmetric transformation of C(sp3)–H bonds is underdeveloped owing to the lack of catalytic systems that can competently discriminate among ubiquitous C–H bonds in organic molecules. This short review aims to outline the challenges and strategies for the catalytic functionalization of C(sp3)–H bonds giving a general and non-exhaustive explanatory approach. Current strategies on the basis of the substrates and reaction mechanisms are summarized in Section 1. Examples of enantioselective C–H bond transformations are then given in Section 2. Finally, in Section 3, an outline of current methodologies towards the direct borylation of C(sp3)–H bonds is described to showcase the importance of developing techniques for catalytic C–H bond chemistry. While we try to cover all excellent reports available in the literature on this topic, any omissions are unintentional, taking note of the most representative examples available.

Metal-catalysed C–H bond activation and borylation

“…In sharp contrast, transition metal-catalysed direct C-H bond activation and borylation reaction occupied a special place in this field of research to prepare a diverse class of organoboron compounds. Significant progress has been made toward the development of transition metal-catalysed C-H borylation [8][9][10][11][12] reactions that resulted in high yields and high selectivity. The formation of the B-C bond is an energetically downhill process.…”

“…In particular, direct C-H bond activation and subsequent functionalization [1][2][3][4][5][6][7] of hydrocarbons has proved as one of the most important methods in chemical science, because it allows easy routes for the production of functionalized complex molecules. In this context, C-H borylation [8][9][10][11][12][13] has attracted special attention because of several important purposes. For example, organoboron compounds can easily be employed in many synthetic transformations in organic synthesis, medicinal chemistry, materials science, fine chemicals, total synthesis of natural products, and so on.…”

Density Functional Theory Studies of the Catalyst Structure–Activity and Selectivity Relationships in Rh(I)-Catalyzed Transfer C–H Borylation of Alkenes

“…Methods enabling the borylation of C–H bonds are attractive for the preparation of synthetically valuable intermediates as well as for the diversity-oriented late-stage modification of complex molecules, − which can utilize a broad range of C–B bond postfunctionalization reactions. − Strategies of C–H functionalization by functional group transfer, often referred to as shuttle catalysis, are particularly appealing, because they typically avoid using highly reactive reagents, thereby improving the scope and utility of the methods. , Inspired by prior works of Marciniec, , Wu, and Lin and Marder, our group recently developed a potent method for the transfer C–H borylation of alkenes using a Rh­(I)-xantphos catalytic system, which offers high functional group tolerance and excellent β-regio- and ( E )-stereoselectivity (Figure a) . However, some challenges remain to be addressed, such as the limited activity of the catalyst especially in the case of reactions for internal alkenes or the control of selectivity to promote formation of other regio- and stereoisomers of the product.…”

Iridium-catalyzed meta-selective C–H borylation of phenol derivatives

“…18 Over the past two decades, significant advancements have been made in this field. [1][2][3][4][5][6] In 2002, Ishiyama, Takagi, Miyaura, and Hartwig independently reported the first iridium-catalyzed distal C-H borylation. [19][20][21] Following Hartwig's seminal discovery, Chattopadhyay reported remote C-H borylation using a bifunctional L-shaped ligand (Scheme 1a), 22 while Itami accomplished para-selective C-H borylation with a bulky ligand.…”

“…Regioselective C–H functionalization is of great significance in synthetic chemistry. Among the various methods, transition-metal-catalyzed C–H borylation stands out 1–6 due to its versatility in converting C–B bonds into C–N, C–D, C–O, C–X, and C–C bonds. 7 In addition, organoboron compounds are widely used in biomarker discovery, 8,9 chemical sensing, 10 bioprobe development, 11 and molecular imaging.…”