Photo- and electro-chemical strategies for the activations of strong chemical bonds.

The employment of light and/or electricity - alternatively to conventional thermal energy - unlocks new reactivity paradigms as tools for chemical substrate activations. This leads to the development of new synthetic reactions and a vast expansion of chemical spaces. This review summarizes recent developments in photo- and/or electrochemical activation strategies for the functionalization of strong bonds - particularly carbon-heteroatom (C-X) bonds - : (1) direct photoexcitation by high energy UV light; (2) activation photoredox catalysis under irradiation with relatively lower energy UVA or blue light; (3) electrochemical reduction; (4) combination of photocatalysis and electrochemistry.

An unexpected synthesis of azepinone derivatives through a metal-free photochemical cascade reaction.

Azepinone derivatives are privileged in organic synthesis and pharmaceuticals. Synthetic approaches to these frameworks are limited to complex substrates, strong bases, high power UV light or noble metal catalysis. We herein report a mild synthesis of azepinone derivatives by a photochemical generation of 2-aryloxyaryl nitrene, [2 + 1] annulation, ring expansion/water addition cascade reaction without using any metal catalyst.

Benzoates as photosensitization catalysts and auxiliaries in efficient, practical, light-powered direct C(sp)-H fluorinations.

Of the methods for direct fluorination of unactivated C(sp)-H bonds, photosensitization of SelectFluor is a promising approach. Although many substrates can be activated with photosensitizing catalysts, issues remain that hamper fluorination of complex molecules. Alcohol- or amine-containing functional groups are not tolerated, fluorination regioselectivity follows factors endogenous to the substrate and cannot be influenced by the catalyst, and reactions are highly air-sensitive.

α-Amino Radical Halogen Atom Transfer Agents for Metallaphotoredox-Catalyzed Cross-Electrophile Couplings of Distinct Organic Halides.

α-Amino radicals from simple tertiary amines were employed as halogen atom transfer (XAT) agents in metallaphotoredox catalysis for cross-electrophile couplings of organic bromides with organic iodides. This XAT strategy proved to be efficient for the generation of carbon radicals from a range of partners (alkyl, aryl, alkenyl, and alkynyl iodides). The reactivities of these radical intermediates were captured by nickel catalysis with organobromides including aryl, heteroaryl, alkenyl, and alkyl bromides, enabling six diverse C-C bond formations.

Dual Gold/Silver Catalysis: Indolizines from 2-Substituted Pyridine Derivatives via a Tandem C(sp)-H Alkynylation/Iminoauration.

A dual gold/silver-catalyzed cascade C(sp)-H alkynylation/iminoauration of 2-substituted pyridines with hypervalent iodine(III) reagents for the synthesis of indolizines is described. This novel reaction involves the formation of an alkynyl Au(III) species, a dual gold/silver-catalyzed C(sp)-H functionalization, and a subsequent iminoauration process. A number of indolizines bearing diverse functionalities were prepared in good to excellent yield.

Synthetic Molecular Photoelectrochemistry: New Frontiers in Synthetic Applications, Mechanistic Insights and Scalability.

Synthetic photoelectrochemistry (PEC) is receiving increasing attention as a new frontier for the generation and handling of reactive intermediates. PEC permits selective single-electron transfer (SET) reactions in a much greener way and broadens the redox window of possible transformations. Herein, the most recent contributions are reviewed, demonstrating exciting new opportunities, namely, the combination of PEC with other reactivity paradigms (hydrogen-atom transfer, radical polar crossover, energy transfer sensitization), scalability up to multigram scale, novel selectivities in SET super-oxidations/reductions and the importance of precomplexation to temporally enable excited radical ion catalysis.

Electro-mediated PhotoRedox Catalysis for Selective C(sp )-O Cleavages of Phosphinated Alcohols to Carbanions.

We report a novel example of electro-mediated photoredox catalysis (e-PRC) in the reductive cleavage of C(sp )-O bonds of phosphinated alcohols to alkyl carbanions. As well as deoxygenations, olefinations are reported which are E-selective and can be made Z-selective in a tandem reduction/photosensitization process where both steps are photoelectrochemically promoted. Spectroscopy, computation, and catalyst structural variations reveal that our new naphthalene monoimide-type catalyst allows for an intimate dispersive precomplexation of its radical anion form with the phosphinate substrate, facilitating a reactivity-determining C(sp )-O cleavage.

Tetrasubstituted 1,3-Enynes by Gold-Catalyzed Direct C(sp)-H Alkynylation of Acceptor-Substituted Enamines.

A gold-catalyzed synthesis of tetrasubstituted 1,3-enynes from hypervalent iodine(III) reagents and activated alkenes is reported. This reaction involves an in situ formed alkynyl Au(III) species and a subsequent direct C(sp)-H functionalization of alkenes, offering 26 enynes in 62-92% yield with excellent functional group tolerance.

Synthesis of Carbazoles and Related Heterocycles from Sulfilimines by Intramolecular C-H Aminations.

While direct nitrene insertions into C-H bonds have become an important tool for building C-N bonds in modern organic chemistry, the generation of nitrene intermediates always requires transition metals, high temperatures, ultraviolet or laser light. We report a mild synthesis of carbazoles and related building blocks through a visible light-induced intramolecular C-H amination reaction. A striking advantage of this new method is the use of more reactive aryl sulfilimines instead of the corresponding hazardous azides.

α-Imino Gold Carbene Intermediates from Readily Accessible Sulfilimines: Intermolecular Access to Structural Diversity.

Catalytic approaches to pharmaceutically important bioactive skeletons through gold carbene intermediates have experienced a dramatic development in the last decade. Although various carbene precursors continue to play an important role in heterocyclic syntheses, these reagents are associated with some drawbacks in terms of functional group tolerance, synthetic methods and safety limitations. A new generation of nitrene transfer reagents was established in 2019: the sulfilimines.

Acyl Migration versus Epoxidation in Gold Catalysis: Facile, Switchable, and Atom-Economic Synthesis of Acylindoles and Quinoline Derivatives.

We report a switchable synthesis of acylindoles and quinoline derivatives via gold-catalyzed annulations of anthranils and ynamides. α-Imino gold carbenes, generated in situ from anthranils and an N,O-coordinated gold(III) catalyst, undergo electrophilic attack to the aryl π-bond, followed by unexpected and highly selective 1,4- or 1,3-acyl migrations to form 6-acylindoles or 5-acylindoles. With the (2-biphenyl)di-tert-butylphosphine (JohnPhos) ligand, gold(I) carbenes experienced carbene/carbonyl additions to deliver quinoline oxides.

Gold(iii)-catalyzed chemoselective annulations of anthranils with N-allylynamides for the synthesis of 3-azabicyclo[3.1.0]hexan-2-imines.

We herein report the gold(iii)-catalyzed selective annulation of anthranils with N-allylynamides under mild conditions. By trapping the in situ-generated α-imino gold carbenes, 3-azabicyclo[3.1.

Synthesis of 2-Aminoindoles through Gold-Catalyzed C-H Annulations of Sulfilimines with N-Arylynamides.

A new gold-catalyzed C-H annulation of sulfilimines with N-phenylynamides is presented. As key intermediates of this operationally simple reaction, the in situ generated α-imino gold carbenes insert into the ortho C-H bonds of the phenyl groups to afford 2-aminoindoles bearing a variety of substitution patterns in high selectivities. This reaction offers a facile approach to biologically important 2-aminoindoles by using inexpensive and readily available starting materials.

Gold(III)-Catalyzed Formal [3 + 2] Annulations of N-Acyl Sulfilimines with Ynamides for the Synthesis of 4-Aminooxazoles.

A gold-catalyzed formal 1,3-dipolar [3 + 2] annulation using readily accessible N-acyl sulfilimines and ynamides is reported. This reaction includes the cleavage of a N-S bond and subsequent C-O bond formation. In total, 30 oxazole derivatives bearing diverse functionalities could be prepared in 43-98% yield from the corresponding sulfilimines and ynamides.

N-Pyridinyl Sulfilimines as a Source for α-Imino Gold Carbenes: Access to 2-Amino-Substituted N-Fused Imidazoles.

Gold-catalyzed formal 1,3-dipolar annulation between readily accessible N-pyridinylsulfilimines and ynamides is reported. A diverse set of imidazole derivatives is prepared from the corresponding sulfilimines and ynamides. These functionalized cyclic products can undergo further transformations to afford diverse imidazole frameworks.

Sulfilimines as Versatile Nitrene Transfer Reagents: Facile Access to Diverse Aza-Heterocycles.

We herein report the unprecedented synthesis of diverse biologically important aza-heterocycles by employing sulfilimines as nitrene transfer reagents. This class of sulfur-based aza-ylides had not been successfully used for gold nitrene transfer before. This work contains an efficient generation of α-imino gold carbenes by N-S cleavage of sulfilimines.

AuBr -Catalyzed Chemoselective Annulation of Isocyanates with 2H-Azirine.

The chemoselective cyclization of isocyanates with 2H-azirine was achieved with AuBr as catalyst. This transfer sets the stage for the synthesis of aromatic oxazole-ureas in a tandem process. The addition of a catalytic amount of phosphite enhances the process enormously.

Investigation of the Interaction between 1,3-Diazaheterocyclic Compounds and the Fat Mass and Obesity-Associated Protein by Fluorescence Spectroscopy and Molecular Modeling.

In this paper, The binding of twelve 1,3-diazaheterocyclic compounds (1a-1 l) to the fat mass and obesity-associated (FTO) protein was investigated by fluorescence, UV-vis absorption spectroscopy and molecular modeling. Results indicated that the intrinsic fluorescence of FTO is quenched by the nine compounds (1a-1i) with a static quenching procedure. No interaction was observed between FTO protein and compounds (1j-1 l).

Synthesis of Novel Imidazo[1,2-a]pyridin-2-amines from Arylamines and Nitriles via Sequential Addition and I2 /KI-Mediated Oxidative Cyclization.

A novel and practical strategy for the construction of imidazo[1,2-a]pyridin-2-amine frameworks has been developed. The present sequential approach involves addition of arylamines to nitriles and I2 /KI-mediated oxidative C-N bond formation without purification of the intermediate amidines. This operationally simple synthetic process provides a facile access to a variety of new 2-amino substituted imidazo[1,2-a]pyridines and related heterocyclic compounds in an efficient and scalable fashion.

Design, synthesis, and biological evaluation of new N(4)-Substituted 2'-deoxy-2'-fluoro-4'-azido cytidine derivatives as potent anti-HBV agents.

A series of new 2'-deoxy-2'-β-fluoro-4'-azido-β-d-arabinofuranosyl cytidine derivatives bearing heteroatom-containing N(4)-substituents were designed and synthesized. Antiviral screening in HepG2.2.

I2/KI-Mediated Oxidative N-N Bond Formation for the Synthesis of 1,5-Fused 1,2,4-Triazoles from N-Aryl Amidines.

An I2/KI-mediated oxidative N-N bond formation reaction is described. This new and environmentally benign approach allows for the convenient synthesis of a variety of 1,2,4-triazolo[1,5-a]pyridines and other 1,5-fused 1,2,4-triazoles from readily available N-aryl amidines in an efficient and scalable fashion.

Synthesis of 2-amino-1,3,4-oxadiazoles and 2-amino-1,3,4-thiadiazoles via sequential condensation and I2-mediated oxidative C–O/C–S bond formation.

2-Amino-substituted 1,3,4-oxadiazoles and 1,3,4-thiadiazoles were synthesized via condensation of semicarbazide/thiosemicarbazide and the corresponding aldehydes followed by I2-mediated oxidative C–O/C–S bond formation. This transition-metal-free sequential synthesis process is compatible with aromatic, aliphatic, and cinnamic aldehydes, providing facile access to a variety of diazole derivatives bearing a 2-amino substituent in an efficient and scalable fashion.