Site‐Selective C(sp³)−H and C(sp²)−H Functionalization of Amines Using a Directing‐Group‐Guided Strategy

Abstract

Amines represent an important class of industrial feedstock as many pharmaceuticals, agrochemicals, petrochemicals, and healthcare products are derived from them. Researchers are developing methodologies for the functionalization of aliphatic and aromatic amines by improving their functionalgroup tolerance, regioselectivity, chemoselectivity, and time efficiency. Among the most studied methods for the derivatization of amines, CÀ H activation is gaining significant interest due to easy-to-follow, environmentally friendly, and time-economic protocols. Transition-metal-catalyzed C(sp 3)À H and C (sp 2)À H activation is a fascinating field of chemistry where the electronics of the structure, functional group characteristics, and nature of the directing group (DG) decide the outcome of the chemical reaction. Under carefully tailored reaction conditions and by a selection of the correct substrates/reagent, site-specific CÀ H functionalization can be achieved at different positions with respect to the amine group. This review provides an overview of the combination of carbon-carbon and carbon-heteroatom functionalizations and describes recent state-of-the-art methodologies, as well as challenges in this emerging field. 1. Introduction 2. α-CÀ H Activation and Functionalization of Amines 3. β-CÀ H Activation and Functionalization of Amines 4. γ-CÀ H Activation and Functionalization of Amines 5. δ-CÀ H Activation and Functionalization of Amines 6. Concluding Remarks

Site‐Selective C(sp3)−H Borylation of 3‐Azabicyclo[3.1.0]hexanes by Cooperative Iridium/Aluminum Catalysis

“… [7–9] From the viewpoint of rapid drug discovery, common intermediates that can participate in rapid diversification are highly desirable [10] . In this context, site‐selective direct C−H functionalization should be one of the ideal transformations [11] . Transition‐metal‐catalyzed C( sp 3 )−H bond functionalization has been well studied in the last few decades.…”

Visible-light-absorbing C–N cross-coupling for the synthesis of hydrazones involving C(sp2)–H/C(sp3)–H functionalization

“…Many catalytic techniques have been used for the selective functionalization of C-H bonds, including those using transition metals, enzymatic systems, and photochemical, electrochemical, and photoredox systems. [1][2][3][4][5][6][7][8][9] Out of these, photoredox catalysis is still growing quickly in various areas of scientific study, including applications to new reaction development, renewable energy, chemical feedstocks, natural product synthesis, and biological applications. [10][11][12][13][14] As a green, potent, and environmentally benign tool for organic synthesis, visible light in conjunction with photoredox catalysis to enable chemical transformations has also become more prominent lately.…”

“…Many catalytic techniques have been used for the selective functionalization of C–H bonds, including those using transition metals, enzymatic systems, and photochemical, electrochemical, and photoredox systems. 1–9…”

Visible-Light-Induced Desaturative β-Alkoxyoxalylation of N-Aryl Cyclic Amines with Difluoromethyl Bromides and H2O Via a Triple Cleavage Process

“…Moreover, the substituted piperidine structural fragment is the most common skeleton of the nitrogenous heterocyclic drugs in Food and Drug Administration (FDA) approved drugs . Nowadays, the direct C(sp 3 )–H functionalization of amines has served as a powerful tool for synthesis of nitrogen heterocycle compounds . For instance, in 2021, Xu’s group achieved α-C(sp 3 )–H carbamylation of aza-heterocycles via a rationally designed photocatalytic system .…”