Skeletal Editing via Transition-Metal-Catalyzed Nitrene Insertion.

Metal-nitrenes are valuable reactive intermediates for synthesis and are widely used to construct biologically relevant scaffolds, complexes and functionalized molecules. The ring expansion of cyclic molecules via single-nitrogen-atom insertion via nitrene or metal-nitrenoid intermediates has emerged as a promising modern strategy for driving advantageous nitrogen-rich compound synthesis. In recent years, the catalytic insertion of a single nitrogen atom into carbocycles, leading to N-heterocycles, has become an important focus of modern synthetic approaches with applications in medicinal chemistry, materials science, and industry.

Skeletal Editing by Hypervalent Iodine Mediated Nitrogen Insertion.

Hypervalent iodine reagents are versatile and readily accessible reagents that have been extensively applied in contemporary synthesis in modern organic chemistry. Among them, iodonitrene (ArI=NR), is a powerful reactive species, widely used for a single-nitrogen-atom insertion reaction, and skeletal editing to construct N-heterocycles. Skeletal editing with reactive iodonitrene components has recently emerged as an exciting approach in modern chemical transformation.

Iron(II)-Catalyzed Aerobic Biomimetic Oxidation of N-Heterocycles.

Herein, an iron(II)-catalyzed biomimetic oxidation of N-heterocycles under aerobic conditions is described. The dehydrogenation process, involving several electron-transfer steps, is inspired by oxidations occurring in the respiratory chain. An environmentally friendly and inexpensive iron catalyst together with a hydroquinone/cobalt Schiff base hybrid catalyst as electron-transfer mediator were used for the substrate-selective dehydrogenation reaction of various N-heterocycles.

Copper-catalyzed functionalization of enynes.

The copper-catalyzed functionalization of enyne derivatives has recently emerged as a powerful approach in contemporary synthesis. Enynes are versatile and readily accessible substrates that can undergo a variety of reactions to yield densely functionalized, enantioenriched products. In this perspective, we review copper-catalyzed transformations of enynes, such as boro- and hydrofunctionalizations, copper-mediated radical difunctionalizations, and cyclizations.

Enantioselective Copper-Catalyzed Borylative Cyclization for the Synthesis of Quinazolinones.

Quinazolinones are common substructures in molecules of medicinal importance. We report an enantioselective copper-catalyzed borylative cyclization for the assembly of privileged pyrroloquinazolinone motifs. The reaction proceeds with high enantio- and diastereocontrol, and can deliver products containing quaternary stereocenters.

Iron(II)-Catalyzed Aerobic Biomimetic Oxidation of Amines using a Hybrid Hydroquinone/Cobalt Catalyst as Electron Transfer Mediator.

Herein we report the first Fe -catalyzed aerobic biomimetic oxidation of amines. This oxidation reaction involves several electron transfer steps and is inspired by biological oxidation in the respiratory chain. The electron transfer from the amine to molecular oxygen is aided by two coupled catalytic redox systems, which lower the energy barrier and improve the selectivity of the oxidation reaction.

Copper-Catalyzed Borylative Couplings with C-N Electrophiles.

Copper-catalyzed borylative multicomponent reactions (MCRs) involving olefins and C-N electrophiles are a powerful tool to rapidly build up molecular complexity. The products from these reactions contain multiple functionalities, such as amino, cyano and boronate groups, that are ubiquitous in medicinal and process chemistry programs. Copper-catalyzed MCRs are particularly attractive because they use a relatively abundant and non-toxic catalyst to selectively deliver high-value products from simple feedstocks such as olefins.

Enantio- and Diastereoselective Synthesis of Homopropargyl Amines by Copper-Catalyzed Coupling of Imines, 1,3-Enynes, and Diborons.

An efficient, enantio- and diastereoselective, copper-catalyzed coupling of imines, 1,3-enynes, and diborons is reported. The process shows broad substrate scope and delivers complex, chiral homopropargyl amines; useful building blocks on the way to biologically-relevant compounds. In particular, functionalized homopropargyl amines bearing up to three contiguous stereocenters can be prepared in a single step.

Catalytic Transfer Hydrogenation Using Biomass as Hydrogen Source.

We developed an operationally simple method for the direct use of biomass-derived chemical entities in a fundamentally important process, such as hydrogenation. Various carbohydrates, starch, and lignin were used for stereoselective hydrogenation. Employing a transition metal catalyst and a novel catalytic system, the reduction of alkynes, alkenes, and carbonyl groups with high yields was demonstrated.

Real time detection of the nerve agent simulant diethylchlorophosphate by nonfluorophoric small molecules generating a cyclization-induced fluorogenic response.

Chemical warfare agents (CWA) are some of the most nefarious weapons, and their possible use in terrorist attacks has led to growing interest in the development of reliable and accurate methods to detect these lethal chemicals. In this paper, we have prepared three nonfluorophores containing 2-(2-hydroxybenzylidene)-malononitrile with various 5-substituents as chemosensor probes for a nerve-agent simulant, diethylchlorophosphate (DCP). The phenolic group of the probes, as the active site, can be rapidly phosphorylated by DCP via nucleophilic substitution and then undergo a simultaneous intramolecular cyclization reaction within 45 s, which can respond to DCP in turn-on fluorescence mode.

Sustainable, Oxidative, and Metal-Free Annulation.

Annulation has received steadily growing interest in the interplay with the increasing emphasis towards selective C-H bond functionalization reactions. Metal-free oxidative annulation through functionalization of inert and abundant C-H bonds offers great improvements in terms of atom- and step-economics as well as reduced waste production under mild reaction conditions. Annulation is considered to be a highly efficient strategy for the construction of cyclic molecules because at least two new bonds are formed within a single reaction step.

A Metal-Free Oxidative Dehydrogenative Diels-Alder Reaction for Selective Functionalization of Alkylbenzenes.

Functionalization of C(sp )-H bonds under metal-free reaction conditions is a great challenge due to poor bond reactivity. A novel metal-free oxidative dehydrogenative Diels-Alder reaction of alkylbenzene derivatives with alkenes through C(sp )-H bond functionalization is described. The developed oxidative method provides a straightforward approach to biologically relevant 1,4-phenanthraquinone and isoindole derivatives from readily available starting materials.

Radical trideuteromethylation with deuterated dimethyl sulfoxide in the synthesis of heterocycles and labelled building blocks.

The potential of deuterated pharmaceuticals is being widely demonstrated. Here we describe the first trideuteromethylation under radical reaction conditions using deuterated dimethyl sulfoxide as a reagent for the synthesis of labelled heterocycles and trideuteromethylated compounds. A broad scope of the developed method for the synthesis of various scaffolds was demonstrated.

[1+1+1] Cyclotrimerization for the Synthesis of Cyclopropanes.

The synthesis of small rings by functionalization of C(sp(3) )-H bonds remains a great challenge. We report for the first time a copper-catalyzed [1+1+1] cyclotrimerization of acetophenone derivatives under mild reaction conditions. The reaction has a broad scope for the stereoselective synthesis of cyclopropanes by trimerization of acetophenone.

Hypervalent Iodine(III) in Direct Oxidative Amination of Arenes with Heteroaromatic Amines.

A novel, mild, and practical method of amination of simple nonfunctionalized arenes under metal free conditions has been developed. The approach allows coupling of electron-rich arenes with amino derivatives of electron-deficient heterocycles providing rapid access to scaffolds of bioactive compounds and is based on the application of the hypervalent iodine(III) reagent as an oxidant. Regioselective functionalization of C-H bonds of arenes by the formation of C-N bonds under organocatalytic conditions was demonstrated.

Copper(I)-Catalyzed Radical Addition of Acetophenones to Alkynes in Furan Synthesis.

A synthesis of multisubstituted furans from readily available acetophenones and electron-deficient alkynes via direct C(sp(3))-H bond functionalization under radical reaction conditions is described. The developed transformation is catalyzed by copper(I) salts using di-tert-butyl peroxide as an external oxidant. This method offers an efficient access to biologically important scaffolds from simple compounds.

Copper-Catalyzed (2+1) Annulation of Acetophenones with Maleimides: Direct Synthesis of Cyclopropanes.

A practical copper-catalyzed direct oxidative cyclopropanation of electron-deficient alkenes with acetophenone derivatives is reported. The dehydrogenative annulation involves a double C-H bond functionalization at the α-position of the ketone using di-tert-butyl peroxide as oxidant. The broad scope of the reaction and excellent functional-group tolerance is demonstrated for the stereoselective synthesis of fused cyclopropanes.

Regioselective annulation of nitrosopyridine with alkynes: straightforward synthesis of N-oxide-imidazopyridines.

We have developed a novel method for the regioselective annulation of 2-nitrosopyridines with variably substituted alkynes under mild reaction conditions. This approach allows the annulation of alkynes with 2-nitrosopyridines under reagent- and catalyst-free reaction conditions. The developed method shows excellent functional group tolerance and provides easy access to N-oxide-imidazo[1,2-a]pyridines.

Metal-free annulation of arenes with 2-aminopyridine derivatives: the methyl group as a traceless non-chelating directing group.

A novel annulation reaction between 2-aminopyridine derivatives and arenes under metal-free conditions is described. The presented intermolecular transformation provided straightforward access to the important pyrido[1,2-a]benzimidazole scaffold under mild reaction conditions. The unprecedented application of the methyl group of methylbenzenes as a traceless, non-chelating, and highly regioselective directing group is reported.

Organocatalytic oxidative annulation of benzamide derivatives with alkynes.

Organocatalytic annulation by functionalization of benzamide derivatives with alkynes has been developed. We report a new approach of cycloaddition under mild reaction conditions using simple catalysts, such as iodobenzene and peracetic acid, as oxidant. Those novel, mild reaction conditions provided a straightforward synthesis of isoquinolones with fast reaction rate.

Synthesis of (E)-nitroolefins via decarboxylative nitration using t-butylnitrite (t-BuONO) and TEMPO.

Nitroolefins are usually synthesized using the Henry reaction. Here we report an alternative metal-free decarboxylative nitration protocol for the preparation of the nitroolefins from α,β-unsaturated carboxylic acids using t-butylnitrite (t-BuONO) and TEMPO. α,β-Unsaturated carboxylic acids bearing β-aromatic and β-heteroaromatic substituents gave (E)-nitroolefins exclusively under mild conditions.

Efficient and stereoselective nitration of mono- and disubstituted olefins with AgNO2 and TEMPO.

Nitroolefin is a common and versatile reagent. Its synthesis from olefin is generally limited by the formation of mixture of cis and trans compounds. Here we report that silver nitrite (AgNO2) along with TEMPO can promote the regio- and stereoselective nitration of a broad range of olefins.