Insights into the Palladium(II)-Catalyzed Wacker-Type Oxidation of Styrene with Hydrogen Peroxide and -Butyl Hydroperoxide.

Wacker oxidations are ubiquitous in the direct synthesis of carbonyl compounds from alkenes. While the reaction mechanism has been widely studied under aerobic conditions, much less is known about such processes promoted with peroxides. Here, we report an exhaustive mechanistic investigation of the Wacker oxidation of styrene using hydrogen peroxide (HO) and -butyl hydroperoxide (TBHP) as oxidants by combining density functional theory and microkinetic modeling.

Total synthesis of complex 2,5-diketopiperazine alkaloids.

The 2,5-diketopiperazine (DKP) motif is present in many biologically relevant, complex natural products. The cyclodipeptide substructure offers structural rigidity and stability to proteolysis that makes these compounds promising candidates for medical applications. Due to their fascinating molecular architecture, synthetic organic chemists have focused significant effort on the total synthesis of these compounds.

Mechanistic Study of Isotactic Poly(propylene oxide) Synthesis using a Tethered Bimetallic Chromium Salen Catalyst.

Initial catalyst dormancy has been mitigated for the enantioselective polymerization of propylene oxide using a tethered bimetallic chromium(III) salen complex. A detailed mechanistic study provided insight into the species responsible for this induction period and guided efforts to remove them. High-resolution electrospray ionization-mass spectrometry and density functional theory computations revealed that a -hydroxide and a bridged 1,2-hydroxypropanolate complex are present during the induction period.

Spontaneous generation of hydrogen peroxide from aqueous microdroplets.

We show HO is spontaneously produced from pure water by atomizing bulk water into microdroplets (1 μm to 20 µm in diameter). Production of HO, as assayed by HO-sensitve fluorescence dye peroxyfluor-1, increased with decreasing microdroplet size. Cleavage of 4-carboxyphenylboronic acid and conversion of phenylboronic acid to phenols in microdroplets further confirmed the generation of HO The generated HO concentration was ∼30 µM (∼1 part per million) as determined by titration with potassium titanium oxalate.

Real-time whole-plant dynamics of heavy metal transport in and by gamma-ray imaging.

Heavy metals such as zinc are essential for plant growth, but toxic at high concentrations. Despite our knowledge of the molecular mechanisms of heavy metal uptake by plants, experimentally addressing the real-time whole-plant dynamics of heavy metal uptake and partitioning has remained a challenge. To overcome this, we applied a high sensitivity gamma-ray imaging system to image uptake and transport of radioactive Zn in whole-plant assays of and the Zn hyperaccumulator .

Mechanistic Study of Ruthenium-Catalyzed C-H Hydroxylation Reveals an Unexpected Pathway for Catalyst Arrest.

We have recently disclosed [(dtbpy)RuCl] as an effective precatalyst for chemoselective C-H hydroxylation of C(sp)-H bonds and have noted a marked disparity in reaction performance between 4,4'-di- tert-butyl-2,2'-bipyridine (dtbpy)- and 2,2'-bipyridine (bpy)-derived complexes. A desire to understand the origin of this difference and to further advance this catalytic method has motivated the comprehensive mechanistic investigation described herein. Details of this reaction have been unveiled through evaluation of ligand structure-activity relationships, electrochemical and kinetic studies, and pressurized sample infusion high-resolution mass spectrometry (PSI-MS).

Ligand-Induced Reductive Elimination of Ethane from Azopyridine Palladium Dimethyl Complexes.

Reductive elimination (RE) is a critical step in many catalytic processes. The reductive elimination of unsaturated groups (aryl, vinyl and ethynyl) from Pd(II) species is considerably faster than RE of saturated alkyl groups. Pd(II) dimethyl complexes ligated by chelating diimine ligands are stable toward RE unless subjected to a thermal or redox stimulus.

Mechanism of Catalytic Oxidation of Styrenes with Hydrogen Peroxide in the Presence of Cationic Palladium(II) Complexes.

Kinetic studies, isotope labeling, and in situ high-resolution mass spectrometry are used to elucidate the mechanism for the catalytic oxidation of styrenes using aqueous hydrogen peroxide (HO) and the cationic palladium(II) compound, [(PBO)Pd(NCMe)][OTf] (PBO = 2-(pyridin-2-yl)benzoxazole). Previous studies have shown that this reaction yields acetophenones with high selectivity. We find that HO binds to Pd(II) followed by styrene binding to generate a Pd-alkylperoxide that liberates acetophenone by at least two competitive processes, one of which involves a palladium enolate intermediate that has not been previously observed in olefin oxidation reactions.

Catalytic Carbonylative Spirolactonization of Hydroxycyclopropanols.

A palladium-catalyzed cascade carbonylative spirolactonization of hydroxycyclopropanols has been developed to efficiently synthesize oxaspirolactones common to many complex natural products of important therapeutic value. The mild reaction conditions, high atom economy, broad substrate scope, and scalability of this new method were highlighted in expedient total syntheses of the Turkish tobacco natural products α-levantanolide and α-levantenolide in two and four steps, respectively. The hydroxycyclopropanol substrates are readily available in one step via a Kulinkovich reaction of the corresponding lactones.

Catalytic Role of Multinuclear Palladium-Oxygen Intermediates in Aerobic Oxidation Followed by Hydrogen Peroxide Disproportionation.

Aerobic oxidation of alcohols are catalyzed by the Pd-acetate compound [LPd(OAc)]2(OTf)2 (L = neocuproine = 2,9-dimethyl-1,10-phenanthroline) to form ketones and the release of hydrogen peroxide, but the latter rapidly undergoes disproportionation. We employ a series of kinetic and isotope labeling studies made largely possible by electrospray ionization mass spectrometry to determine the role of intermediates in causing this complex chemical transformation. The data suggested that multiple catalytic paths for H2O2 disproportionation occur, which involve formation and consumption of multinuclear Pd species.

Un-collimated single-photon imaging system for high-sensitivity small animal and plant imaging.

In preclinical single-photon emission computed tomography (SPECT) system development the primary objective has been to improve spatial resolution by using novel parallel-hole or multi-pinhole collimator geometries. However, such high-resolution systems have relatively poor sensitivity (typically 0.01-0.

Regioselective Asao-Yamamoto benzannulations of diaryl acetylenes.

Asao-Yamamoto benzannulations transform diarylalkynes into 2,3-diarylnaphthalenes, and regioselective variants of this reaction are of interest for synthesizing substituted polycyclic aromatic systems. It is shown that regioselective cycloadditions occur when one alkyne carbon preferentially stabilizes developing positive charge. Simple calculations of the relative energies of carbocations localized at each alkyne carbon of a substrate predict the regioselectivity, which is not eroded by bulky substituents, including 2,6-disubstituted aryl groups.

The effects of amphetamine, butorphanol, and their combination on cocaine self-administration.

There have been recent calls to examine the efficacy of drug-combination therapies in the treatment of substance use disorders. The purpose of the present study was to examine the ability of a novel stimulant-opioid combination to reduce cocaine self-administration, and to compare these effects to those of each drug administered alone. To this end, male Long-Evans rats were implanted with intravenous catheters and trained to self-administer cocaine under positive reinforcement contingencies.

Access to a running wheel decreases cocaine-primed and cue-induced reinstatement in male and female rats.

Background: Relapse to drug use after a period of abstinence is a persistent problem in the treatment of cocaine dependence. Physical activity decreases cocaine self-administration in laboratory animals and is associated with a positive prognosis in human substance-abusing populations. The purpose of this study was to examine the effects of long-term access to a running wheel on drug-primed and cue-induced reinstatement of cocaine-seeking behavior in male and female rats.

The effects of aerobic exercise on cocaine self-administration in male and female rats.

Rationale: In drug self-administration procedures, extended-access test sessions allow researchers to model maladaptive patterns of excessive and escalating drug intake that are characteristic of human substance-abusing populations.

Objectives: The purpose of the present study was to examine the ability of aerobic exercise to decrease excessive and escalating patterns of drug intake in male and female rats responding under extended-access conditions.

Methods: Male and female Long-Evans rats were obtained at weaning and divided into sedentary (no running wheel) and exercising (running wheel) groups immediately upon arrival.

The effects of repeated opioid administration on locomotor activity: II. Unidirectional cross-sensitization to cocaine.

Sensitization refers to an increase in sensitivity to the effects of a drug and is believed to play a role in the etiology of substance use disorders. Cross-sensitization has been observed between drugs from different pharmacological classes and may play a role in the escalation of drug use in polydrug-abusing populations. The purpose of this study was to examine cross-sensitization between opioids and cocaine and to determine the extent to which cross-sensitization is mediated by an opioid's selectivity for mu, kappa, and delta receptors.