C–H activation has surfaced as an increasingly powerful tool for molecular sciences, with notable applications to material sciences, crop protection, drug discovery, and pharmaceutical industries, among others. Despite major advances, the vast majority of these C–H functionalizations required precious 4d or 5d transition metal catalysts. Given the cost-effective and sustainable nature of earth-abundant first row transition metals, the development of less toxic, inexpensive 3d metal catalysts for C–H activation has gained considerable recent momentum as a significantly more environmentally-benign and economically-attractive alternative. Herein, we provide a comprehensive overview on first row transition metal catalysts for C–H activation until summer 2018.

3d Transition Metals for C-H Activation.

Seven kinds of sp3 α-C–H activation/C–C formation reactions of alcohols and ethers have been reviewed in this tutorial review, from the viewpoint of both methodology and synthetic application, towards the efficiency, chemo-, regio- and stereoselectivity, catalytic system, substrate scope and mechanistic study. Section 2 describes radical-mediated α-C–H activation and addition/elimination of ethers with unsaturated (CC and CC) species. Sections 3–8 discuss the α-C–H activation and additions of alcohols and/or ethers with unsaturated (CC, CC, CO and CN) compounds, which involve the key processes of radical mediation, carbenoid insertion, 1,5-H-migration, oxidative dehydrogenation coupling, transfer hydrogenative coupling, and metal-mediated CC insertion into the C–H bond.

Direct Sp3α-C-H activation and functionalization of alcohol and ether.

The article discusses the mechanisms and the applications in organic synthesis, materials, supramolecular, and polymer synthesis of most organic reactions mediated by single electron transfer. Each reaction or class of reactions will be discussed by starting with the original discovery publication, followed by a summary of all or most review articles published in the field, and a discussion of the mechanism(s) and of the most important methodologic and synthetic developments since the most recent review was published. The mechanisms of most organic reactions are considered to proceed by two-electron transfer pathways, even though both biology and radical chemistry rely extensively on one-electron transfer processes. Radicals generated by homolytic cleavage at high temperature were traditionally employed in the industrial production of polymers and to a lesser extent in the synthesis of organic molecules.

Single electron transfer in radical ion and radical-mediated organic, materials and polymer synthesis.

Transition-metal-catalyzed C H functionalization for the atomand step-economical synthesis of functional molecules has attracted tremendous efforts in both academia and industry. The advantages of this method are the high efficiency, low cost, and minimal environmental impact. Heteroatom-containing molecules are abundant in natural products, pharmaceuticals, and materials. It is highly desirable to synthesize these molecules and their derivatives by direct C H functionalization. Metal carbene insertion into a C H bond adjacent to an oxygen atom presents an efficient synthetic approach to ether derivatives (Scheme 1, Meth-

Iron-catalyzed C-C bond formation by direct functionalization of C-H bonds adjacent to heteroatoms.

Title reaction proceeds in the absence of transition metal catalysts, is operationally simple and tolerates a wide variety of functional groups like cyano, amide, aromatic halide, ether, ketone groups and C—C double bonds.

Bu4NI‐Catalyzed C ? O Bond Formation by Using a Cross‐Dehydrogenative Coupling (CDC) Reaction

A simple and rapid procedure for the almost quantitative reduction of aromatic aldehydes, ketones, diketones and oxo aldehydes to alcohols by use of TiCl3/NH3 in aqueous methanol solution is reported. The reducing system distinguishes between different classes of aldehydes and/or ketones, and many functionalities that usually do not survive under reducing conditions are tolerated well. The concept of reversal of chemoselectivity has also been developed. A mechanism based on two sequential one-electron transfers from TiIII to the carbonyl carbon atom is proposed, the second SET becoming operative only in the presence of ammonium ion (either added or formed in situ). (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Facile Reduction of Aromatic Aldehydes, Ketones, Diketones and Oxo Aldehydes to Alcohols by an Aqueous TiCl3/NH3 System: Selectivity and Scope.

tert-Butoxy radical, generated by Ti(III)-one electron reduction of tert-butylhydroperoxide, selectively abstracts an α-H atom from ethers. The resulting α-ethereal radicals add to the C-atom of methylene iminium salts, formed in situ under aqueous acidic conditions, leading to a one-pot aminomethylation of ethers at room temperature. The aminoalkylation of ethers is also considered and the role of the metal ion is discussed.

A Free Radical Mannich Type Reaction: Selective α-CH Aminomethylation of Ethers by Ti(III)/t-BuOOH System under Aqueous Acidic Conditions.

Processo per la produzione di fenolo e cicloesanone

Procedimento per l'ossidazione di idrocarburi alchilaromatici catalizzata da N-idrossiderivati

The tert-butoxyl radical, generated by the aqueous TiIII/TBHP system, abstracts an H atom from alcoholic cosolvents (EtOH, iPrOH), leading to α-hydroxyalkyl radicals thatreduce aromatic aldehydes to the corresponding 1,2-diols. The reactivities observed are explained by resonance stabilization of the α-hydroxybenzyl radicals formed in the electron-transfer (ET) process. Good Hammett-type correlations are obtained. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Nadia Pastori

Papers

Facile Reduction of Aromatic Aldehydes, Ketones, Diketones and Oxo Aldehydes to Alcohols by an Aqueous TiCl3/NH3 System: Selectivity and Scope.

A Free Radical Mannich Type Reaction: Selective α-CH Aminomethylation of Ethers by Ti(III)/t-BuOOH System under Aqueous Acidic Conditions.

Processo per la produzione di fenolo e cicloesanone

Procedimento per l'ossidazione di idrocarburi alchilaromatici catalizzata da N-idrossiderivati

Reductive Coupling of Aromatic Aldehydes Promoted by an Aqueous TiCl3/tBuOOH System in Alcoholic Cosolvents.