Conventional methods for carrying out carbon–hydrogen functionalization and carbon–nitrogen bond formation are typically conducted at elevated temperatures, and rely on expensive catalysts as well as the use of stoichiometric, and perhaps toxic, oxidants. In this regard, electrochemical synthesis has recently been recognized as a sustainable and scalable strategy for the construction of challenging carbon–carbon and carbon–heteroatom bonds. Here, electrosynthesis has proven to be an environmentally benign, highly effective and versatile platform for achieving a wide range of nonclassical bond disconnections via generation of radical intermediates under mild reaction conditions. This review provides an overview on the use of anodic electrochemical methods for expediting the development of carbon–hydrogen functionalization and carbon–nitrogen bond formation strategies. Emphasis is placed on methodology development and mechanistic insight and aims to provide inspiration for future synthetic applications in the field of electrosynthesis.

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Electrochemical strategies for C-H functionalization and C-N bond formation.

ConspectusMerging the characteristics of transfer hydrogenation and carbonyl addition, we have developed a new class of catalytic enantioselective C–C bond formations. In these processes, hydrogen transfer between alcohols and π-unsaturated reactants generates carbonyl–organometal pairs that combine to deliver products of addition. On the basis of this mechanistic paradigm, lower alcohols are converted directly to higher alcohols in the absence of premetalated reagents or discrete alcohol-to-carbonyl redox reactions. In certain cases, due to a pronounced kinetic preference for primary versus secondary alcohol dehydrogenation, diols and higher polyols are found to engage in catalytic stereo- and site-selective C–C bond formation—a capability that further enhances efficiency by enabling skeletal construction events without extraneous manipulations devoted to the installation and removal of protecting groups. While this Account focuses on redox-neutral couplings of alcohols, corresponding aldehyde reductive ...

Catalytic Enantioselective Carbonyl Allylation and Propargylation via Alcohol-Mediated Hydrogen Transfer: Merging the Chemistry of Grignard and Sabatier

Chemoselective functionalizations of intrinsically less reactive C(sp3)–H bonds of alkyl nitriles are of particular interest to the chemical community because these strategies provide opportunities for the introduction of important cyanoalkyl groups onto target frameworks in a step-economical fashion. In recent years, the introduction of nitrile-containing alkyl radicals in tandem radical additions and oxidative couplings has inarguably brought chemists a new radical reaction platform for the diverse synthesis of natural products and pharmaceuticals. Compared with the wide applications of various C-centered radicals adjacent to a heteroatom, however, nitrile-containing alkyl radicals remain largely unexplored. New methods for C(sp3)–H bond oxidative functionalization of alkyl nitriles and new mechanistic manifolds would result in the development of a broad range of novel reactions. Therefore, this review will give an overview of various types of radical cyanoalkylation using the key alkyl nitrile reactant...

http://pubs.acs.org/doi/pdf/10.1021/acscatal.7b03334

Recent Advances in Radical-Initiated C(sp3)–H Bond Oxidative Functionalization of Alkyl Nitriles

Construction of C-C bonds via alkoxy radical-mediated remote C(sp3)-H functionalization is largely unexplored, as it is a formidable challenge to directly generate alkoxy radicals from alcohols due to the high bond dissociation energy (BDE) of O-H bonds. Disclosed herein is a practical and elusive metal-free alcohol-directed heteroarylation of remote unactivated C(sp3)-H bonds. Phenyliodine bis(trifluoroacetate) (PIFA) is used as the only reagent to enable the coupling of alcohols and heteroaryls. Alkoxy radicals are readily generated from free alcohols under the irradiation of visible light, which trigger the regioselective hydrogen-atom transfer (HAT). A wide range of functional groups are compatible with the mild reaction conditions. Two unactivated C-H bonds are cleaved and one new C-C bond is constructed during the reaction. This protocol provides an efficient strategy for the late-stage functionalization of alcohols and heteroaryls.

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Metal-free alcohol-directed regioselective heteroarylation of remote unactivated C(sp 3 )-H bonds

http://spiral.imperial.ac.uk/bitstream/10044/1/42954/2/Sulfides-N-O-transfer-Chemcommun-SUBMT%20REVISED%20.pdf

Synthesis of NH-sulfoximines from sulfides by chemoselective one-pot N- and O-transfers

Oxygen-containing heterocycles are an important class of compounds with diverse biological activities. In recent years, direct α-C–H functionalization of inexpensive and abundant readily available ethers and alcohols by oxidative radical cross-coupling with different nucleophilic partners (C–H, N–H, O–H and S–S), leading to the construction of C–C and C–X (X=C, N, O, S) bonds, has emerged as one of the vital strategies among oxidative cross-coupling reactions. Owing to the features of being atom-economic, environmentally benign, having a simple operation and biologically properties, a series of ether α-C(sp3)–H bond activation reactions have been developed by metal or metal-free systems via the radical oxidative coupling pathway, since the radical oxidative coupling reactions have wide range of applications. This review aims to highlight the recent advances in direct α-C(sp3)–H bond functionalization of ethers and alcohols via radical oxidative process.

Recent Advances of Oxidative Radical Cross-Coupling Reactions: Direct α-C(sp3)–H Bond Functionalization of Ethers and Alcohols

Gold‐Catalyzed, Iodine(III)‐Mediated Direct Acyloxylation of the Unactivated C(sp3)–H Bonds of Methyl Sulfides

A highly effective oxidative thiyl radical addition/cyclization of N-methacryloylbenzamides was explored using dioxygen as the sole terminal oxidant without the use of precious and/or toxic transition-metal catalysts. This method provides convenient access to a variety of useful sulfide-containing 4,4-disubstituted isoquinoline-1,3-diones by constructing C–S and C–C bonds in one step.

Aerobic thiyl radical addition/cyclization of N-methacryloyl benzamides for the synthesis of isoquinoline-1,3(2H,4H)-dione derivatives

Palladium catalyzed aroylation of NH-sulfoximines with aryl halides using chloroform as the CO precursor

An ammonium iodide catalyzed direct oxidative coupling of silanes with alcohols to give various alkoxysilane derivatives was discovered. tert-Butyl hydroperoxide proved to be an efficient oxidant for this transformation. Attractive features of this protocol include its transition-metal-free nature and the mild reaction conditions.

Pailla Santhosh Kumar

Papers

Recent Advances of Oxidative Radical Cross-Coupling Reactions: Direct α-C(sp3)–H Bond Functionalization of Ethers and Alcohols

Gold‐Catalyzed, Iodine(III)‐Mediated Direct Acyloxylation of the Unactivated C(sp3)–H Bonds of Methyl Sulfides

Aerobic thiyl radical addition/cyclization of N-methacryloyl benzamides for the synthesis of isoquinoline-1,3(2H,4H)-dione derivatives

Palladium catalyzed aroylation of NH-sulfoximines with aryl halides using chloroform as the CO precursor

Metal-Free Ammonium Iodide Catalyzed Oxidative Dehydrocoupling of Silanes with Alcohols