Harnessing the Reactivity of Nitroarene Radical Anions to Create Quinoline N-Oxides by Electrochemical Reductive Cyclization.

Electrochemical reduction of 2-allyl-substituted nitroarenes using a simple, undivided electrochemical cell with non-precious electrodes to generate nitroarene radical anions was developed. The nitroarene radical anion intermediates participate in 1,5-hydrogen atom transfer reactions to construct quinoline N-oxides bearing aryl-, heteroaryl-, alkenyl-, benzyl-, sulfonyl-, or carboxyl groups.

Iodine(III)-Catalyzed Oxidative Cyclization of Aryl Amines to Construct -Alkylbenzimidazoles.

An I(III)-catalyzed oxidative cyclization reaction using selectfluor as the oxidant was developed that converts -substituted anilines to benzimidazoles. The mild reaction requires as little as 0.5 mol % of iodobenzene, and its scope is broad: electron-withdrawing or electron-releasing groups on the aniline portion are tolerated, and cyclic or acyclic -alkylamines are permitted as -substituents.

The Development and Mechanistic Study of an Iron-Catalyzed Intramolecular Nitroso Ene Reaction of Nitroarenes.

An intramolecular iron-catalyzed nitroso ene reaction was developed to afford six- or seven-membered -heterocycles from nitroarenes using an earth abundant iron catalyst and phenylsilane as the terminal reductant. The reaction can be triggered using as little as 3 mol % of iron(II) acetate and 3 mol % of 4,7-dimethoxyphenanthroline as the ligand. The scope of the reaction is broad tolerating a range of electron-releasing or electron-withdrawing substituents on the nitroarene, and the -substituent can be modified to diastereoselectively construct benzoxazines, dihydrobenzothiazines, tetrahydroquinolines, tetrahydroquinoxalines, or tetrahydrobenzooxazepines.

Iodine(III)-Mediated Oxidation of Anilines to Construct Dibenzazepines.

The development of an efficient process that produces bioactive medium-sized N-heterocyclic scaffolds from 2-substituted anilines using either iodosobenzene or (bis(trifluoroacetoxy)iodo)-benzene is reported. The tether between the sulfonamide and the aryl group can be varied to access dihydroacridine-, dibenzazepine-, or dibenzazocine scaffolds. While substitution on the aniline portion is limited to electron-neutral- or electron-poor groups, a broader range of functional groups are tolerated on the ortho-aryl substituent and site selective C-NAr bond formation can be achieved.

Recent Advances to Mediate Reductive Processes of Nitroarenes Using Single-Electron Transfer, Organomagnesium, or Organozinc Reagents.

Recent advances in the development of reductive reactions of nitroarenes using organomagnesium-, organozinc-, and single electron transfer reagents is discussed within this review. The review is divided into the following sections: IntroductionOrganomagnesium-mediated reductive reactionsOrganozinc- and zinc-mediated reductive reactionsIodine-catalyzed redox cyclizationsTitanium(III)-mediated reductive cyclizationsSulfur-mediated reductive reactionsAlkoxide-mediated reductive reactions4,4'-Bipyridine-mediated reductive reactionsVisible light-driven reductive amination reactionsElectrochemical reductive reactionsConclusion.

Cu-Catalyzed Cross-Coupling of Nitroarenes with Aryl Boronic Acids to Construct Diarylamines.

The development and study of a simple copper-catalyzed reaction of nitroarenes with aryl boronic acids to form diarylamines that uses phenyl silane as the stoichiometric terminal reductant is described. This cross-coupling reaction requires as little as 2 mol % of CuX and 4 mol% of diphosphine for success and tolerates a broad range of functional groups on either the nitroarene or the aryl boronic acid with to afford the amine in good yield. Mechanistic investigations established that the cross-coupling reaction proceeds via a nitrosoarene intermediate and that copper is required to catalyze both the deoxygenation of the nitroarene to afford the nitrosoarene and C-NAr bond formation of the nitrosoarene with the aryl boronic acid.

Rh(II)-Catalyzed Intermolecular -Aryl Aziridination of Olefins Using Nonactivated N Atom Precursors.

The development of the first intermolecular Rh(II)-catalyzed aziridination of olefins using anilines as nonactivated N atom precursors and an iodine(III) reagent as the stoichiometric oxidant is reported. This reaction requires the transfer of an -aryl nitrene fragment from the iminoiodinane intermediate to a Rh(II) carboxylate catalyst; in the absence of a catalyst only diaryldiazene formation was observed. This -aryl aziridination is general and can be successfully realized by using as little as 1 equiv of the olefin.

Recent Advances in the Development of Catalytic Methods that Construct Medium-ring Lactams, Partially Saturated Benzazepines and their Derivatives.

Recent catalytic methods to construct medium-sized lactams and partially saturated benzazepines and their derivatives are surveyed. The review is divided into the following sections: 1 Introduction 2 Non-Transition Metal Catalyzed Reactions 2.1 Beckmann Rearrangement 2.

Counterion Control of t-BuO-Mediated Single Electron Transfer to Nitrostilbenes to Construct N-Hydroxyindoles or Oxindoles.

tert-Butoxide unlocks new reactivity patterns embedded in nitroarenes. Exposure of nitrostilbenes to sodium tert-butoxide was found to produce N-hydroxyindoles at room temperature without an additive. Changing the counterion to potassium changed the reaction outcome to yield solely oxindoles through an unprecedented dioxygen-transfer reaction followed by a 1,2-phenyl migration.

I(III)-Catalyzed Oxidative Cyclization-Migration Tandem Reactions of Unactivated Anilines.

An I(III)-catalyzed oxidative cyclization-migration tandem reaction using Selectfluor as the oxidant was developed that converts unactivated anilines into 3-indoles is reported herein. The reaction requires as little as 1 mol % of the iodocatalyst and is mild, tolerating pyridine and thiophene functional groups, and the dependence of the diastereoselectivity of the process on the identity of the iodoarene or iodoalkane precatalyst suggests that the catalyst is present for the stereochemical determining C-N bond forming step.

Oxidation of Nonactivated Anilines to Generate -Aryl Nitrenoids.

A low-temperature, protecting-group-free oxidation of 2-substituted anilines has been developed to generate an electrophilic -aryl nitrenoid intermediate that can engage in C-NAr bond formation to construct functionalized -heterocycles. The exposure of 2-substituted anilines to PIFA and trifluoroacetic acid or 10 mol % Sc(OTf) triggers nitrenoid formation, followed by productive and selective C-NAr and C-C bond formation to yield spirocyclic- or bicyclic 3-indoles or benzazepinones. Our experiments demonstrate the breadth of these oxidative processes, uncover underlying fundamental elements that control selectivity, and demonstrate how the distinct reactivity patterns embedded in -aryl nitrenoid reactive intermediates can enable access to functionalized 3-indoles or benzazepinones.

Intramolecular Pd-Catalyzed Reductive Amination of Enolizable sp-C-H Bonds.

A palladium-catalyzed reductive cyclization of nitroarenes has been designed to construct sp-C-NHAr bonds from sp-C-H bonds by using an enolizable nucleophile to intercept a nitrosoarene intermediate. Exposure of -substituted nitroarenes to 5 mol % of Pd(OAc) and 10 mol % of phenanthroline under 2 atm of CO constructs partially saturated 5-, 6-, or 7-membered -heterocycles using α-pyridyl carboxylates, malonates, 1,3-dimethylbarbituric acid, 1,3-diones, or difurans as the nucleophile.

Controlling the Selectivity Patterns of Au-Catalyzed Cyclization-Migration Reactions.

As little as 2 mol % of (XPhos)AuNTf catalyzes the transformation of a broad range of o-acetylene-substituted styrenes into 1,2-dihydronaphthalenes. Our data suggests that this transformation occurs via a gold-stabilized cyclopropyl carbinyl cation, which triggers either a [1,2] carboxylate shift or a less favorable [1,2] aryl shift. The relative rates of these migrations can be controlled by the identity of the ligand or by stabilizing the mesomeric cation.

Generation of controllable gaseous HS concentrations using microfluidics.

Hydrogen sulfide (HS) plays an important role as an intercellular and intracellular signaling molecule, yet its targets are not well understood. As a molecule it easily evaporates and it is hard to acquire stable concentration for in vitro studies, constituting a major problem for the field to identify its downstream targets and function. Here we develop a microfluidic system that can provide consistent and controllable HS levels in contrast to the current method of delivering large bolus doses to cells.

A novel chemical inducer of quorum sensing acts by inhibiting the pheromone-degrading endopeptidase PepO.

Bacteria produce chemical signals (pheromones) to coordinate behaviors across a population in a process termed quorum sensing (QS). QS systems comprising peptide pheromones and their corresponding Rgg receptors are widespread among and may be useful targets for manipulating microbial behaviors, like suppressing virulence. The Rgg2/3 QS circuit of the human pathogen controls genes affecting resistance to host lysozyme in response to short hydrophobic pheromones (SHPs).

Synthesis and Properties of New N-Heteroheptacenes for Solution-Based Organic Field Effect Transistors.

A series of N-heteroheptacenes was synthesized from ortho-thiophene-substituted aryl azides using a Rh -catalyzed C-H bond amination reaction to construct the thienoindole moieties. This reaction tolerated the presence of electron-donating or withdrawing groups on the aryl azide without adversely affecting the yield of the amination reaction. The central thiophene ring was created from two thienoindole pieces through a Pd-catalyzed Stille reaction to install the thioether followed by a Cu-mediated Ullman reaction to trigger the cyclization.

Achieving Site Selectivity in Metal-Catalyzed Electron-Rich Carbene Transfer Reactions from N-Tosylhydrazones.

Catalyst control of the site-selectivity of electron-rich alkyl, aryl disubstituted carbenes generated in situ from o-alkenyl-substituted N-tosylhydrazones was achieved in this study. Exposure of these substrates to copper iodide triggered the formation of α-alkoxy 2H-naphthalenones. This investigation established that changing the catalyst to a rhodium(II) carboxylate turned off cyclization and migration of the electron-rich metal carbene with the β-carboxylate and turned on allylic C-H bond functionalization to diastereoselectively afford 1H-indenes.

Nitroarenes as the Nitrogen Source in Intermolecular Palladium-Catalyzed Aryl C-H Bond Aminocarbonylation Reactions.

A three-component palladium-catalyzed aminocarbonylation of aryl and heteroaryl sp C-H bonds using nitroarenes as the nitrogen source was achieved using Mo(CO) as the reductant and origin of the CO. This intermolecular C-H bond functionalization does not requires any exogenous ligand to be added, and our mechanism experiments indicate that the palladacycle catalyst serves two roles in the aminocarbonylation reaction: reduce the nitroarene to a nitrosoarene and activate the sp C-H bond.

Rh(II)-Catalyzed Ring Expansion of Cyclobutanol-Substituted Aryl Azides To Access Medium-Sized N-Heterocycles.

A new reactivity pattern of Rh(II)-N-arylnitrenes was discovered that facilitates the synthesis of medium-sized N-heterocycles from ortho-cyclobutanol-substituted aryl azides. The key ring-expansion step of the catalytic cycle is both chemoselective and stereospecific. Our mechanistic experiments implicate the formation of a rhodium N-arylnitrene catalytic intermediate and reveal that sp C-H bond amination of this electrophilic species is competitive with the ring-expansion process.

Time-Gated Detection of Cystathionine γ-Lyase Activity and Inhibition with a Selective, Luminogenic Hydrogen Sulfide Sensor.

Herein, we report the design, synthesis, and characterization of a lanthanide complex-based probe for the time-gated luminescence detection of hydrogen sulfide (H S) in aqueous media. The probe's unique sensing mechanism relies on the selective reduction of azide to amine by sulfide, followed by intramolecular cyclization to form a quinolinone. The quinolinone is a sensitizer that absorbs near-UV light and transfers excitation energy to coordinated Tb or Eu ions to trigger a strong "turn-on" luminescence response with ms-scale lifetimes characteristic of lanthanide complexes.

Control of the Chemoselectivity of Metal N-Aryl Nitrene Reactivity: C-H Bond Amination versus Electrocyclization.

A mechanism study to identify the elements that control the chemoselectivity of metal-catalyzed N-atom transfer reactions of styryl azides is presented. Our studies show that the proclivity of the metal N-aryl nitrene to participate in sp-C-H bond amination or electrocyclization reactions can be controlled by either the substrate or the catalyst. Electrocyclization is favored for mono-β-substituted and sterically noncongested styryl azides, whereas sp-C-H bond amination through an H-atom abstraction-radical recombination mechanism is preferred when a tertiary allylic reaction center is present.

Diborane-Mediated Deoxygenation of o-Nitrostyrenes To Form Indoles.

A mild, transition metal-free, diborane-mediated deoxygenation of nitro groups was discovered that in situ generates nitrosoarene reactive intermediates. This new reactivity mode of B2pin2 was leveraged to construct indoles from o-nitrostyrenes through a reductive-cyclization reaction that exhibits a Hammett ρ-value of +0.97 relative to σpara values.

Mechanism of Rh2(II)-Catalyzed Indole Formation: The Catalyst Does Not Control Product Selectivity.

Possible mechanisms for Rh-promoted indole formation from vinyl/azidoarenes were examined computationally, and a mechanism is proposed in which the Rh catalyst promotes generation of a nitrene but is not directly involved in cyclization.