The activation of carbon-fluorine (C-F) bonds is an important topic in synthetic organic chemistry. Metal-mediated and -catalyzed elimination of β- or α-fluorine proceeds under milder conditions than oxidative addition to C-F bonds. The β- or α-fluorine elimination is initiated from organometallic intermediates having fluorine substituents on carbon atoms β or α to metal centers, respectively. Transformations through these elimination processes (C-F bond cleavage), which are typically preceded by carbon-carbon (or carbon-heteroatom) bond formation, have been increasingly developed in the past five years as C-F bond activation methods. In this Minireview, we summarize the applications of transition-metal-mediated and -catalyzed fluorine elimination to synthetic organic chemistry from a historical perspective with early studies and from a systematic perspective with recent studies.

Transition-Metal-Mediated and -Catalyzed C-F Bond Activation by Fluorine Elimination.

Tetrahydroquinoline is one of the most important simple nitrogen heterocycles, being widespread in nature and present in a broad variety of pharmacologically active compounds. This Review summarizes the progress achieved in the chemistry of tetrahydroquinolines, with emphasis on their synthesis, during the period from mid-2010 to early 2018.

Progress in the Chemistry of Tetrahydroquinolines.

Advances of azide-alkyne cycloaddition-click chemistry over the recent decade

Role of sulphur-heterocycles in medicinal chemistry: An update

Transition metal-catalyzed aryl C-H activation is a powerful synthetic tool as it offers step and atom-economical routes to site-selective functionalization. Compared with proximal ortho-C-H activation, distal (meta- and/or para-) C-H activation remains more challenging due to the inaccessibility of these sites in the formation of energetically favorable organometallic pretransition states. Directing the catalyst toward the distal C-H bonds requires judicious template engineering and catalyst design, as well as prudent choice of ligands. This review aims to summarize the recent elegant discoveries exploiting directing group assistance, transient mediators or traceless directors, noncovalent interactions, and catalyst and/or ligand selection to control distal C-H activation.

Arene diversification through distal C(sp2)-H functionalization.

Progress in 1,3-dipolar cycloadditions in the recent decade: an update to strategic development towards the arsenal of organic synthesis

gem-Difluorinated alkenes are readily accessible building blocks that can undergo functionalization to provide a broad spectrum of fluorinated and non-fluorinated products. Herein, we review recent (since 2017) transition metal-catalyzed transformations of these specialized alkenes and summarize general reactivity patterns of these reactions. Many transition metal-catalyzed reactions undergo net C-F bond functionalization reactions to deliver monofluorinated products. These reactions typically proceed through β-fluoro alkylmetal intermediates that readily eliminate a β-fluoride to deliver monofluoroalkene products. A second series of reactions exploit coinage metal fluorides to add F- to the gem-difluorinated alkene, and further functionalization delivers trifluoromethyl-containing products. In stark contrast, few transition metal-catalyzed reactions proceed in net "fluorine-retentive processes" to deliver difluoromethylene-based products.

Recent Advances in Transition Metal-Catalyzed Functionalization of gem-Difluoroalkenes.

Cross-Dehydrogenating Coupling of Aldehydes with Amines/R-OTBS Ethers by Visible-Light Photoredox Catalysis: Synthesis of Amides, Esters, and Ureas.

Transition metal-catalysed C-H functionalization and decarboxylative coupling are two of the most notable synthetic strategies developed in the past 30 years. Here, we connect these two reaction pathways using bases and a simple Pd-based catalyst system to promote a para-selective C-H functionalization reaction from benzylic electrophiles. Experimental and computational mechanistic studies suggest a pathway that involves an uncommon Pd-catalysed dearomatization of the benzyl moiety followed by a base-enabled rearomatization through a formal 1,5-hydrogen migration. This reaction complements 'C-H activation' strategies that convert inert C-H bonds into C-metal bonds prior to C-C bond formation. Instead, this reaction exploits an inverted sequence and promotes C-C bond formation prior to deprotonation. These studies provide an opportunity to develop general para-selective C-H functionalization reactions from benzylic electrophiles and show how new reactive modalities may be accessed with careful control of the reaction conditions.

Suvajit Koley

Papers

Advances of azide-alkyne cycloaddition-click chemistry over the recent decade

Progress in 1,3-dipolar cycloadditions in the recent decade: an update to strategic development towards the arsenal of organic synthesis

Recent Advances in Transition Metal-Catalyzed Functionalization of gem-Difluoroalkenes.

Cross-Dehydrogenating Coupling of Aldehydes with Amines/R-OTBS Ethers by Visible-Light Photoredox Catalysis: Synthesis of Amides, Esters, and Ureas.

Connecting remote C-H bond functionalization and decarboxylative coupling using simple amines.