Pd-catalyzed aerobic oxidative coupling of vinylboronic acids and electronically unbiased alkyl olefins provides regioselective access to 1,3-disubstituted conjugated dienes. Catalyst-controlled ...regioselectivity is achieved by using 2,9-dimethylphenanthroline as a ligand. The observed regioselectivity is opposite to that observed from a traditional (nonoxidative) Heck reaction between a vinyl bromide and an alkene. DFT computational studies reveal that steric effects of the 2,9-dimethylphenanthroline ligand promote C–C bond formation at the internal position of the alkene.
Biomimetic aerobic oxidation of primary benzylic amines has been achieved by using a quinone catalyst. Excellent selectivity is observed for primary, unbranched benzylic amines relative to ...secondary/tertiary amines, branched benzylic amines, and aliphatic amines. The exquisite selectivity for benzylic amines enables oxidative self-sorting within dynamic mixtures of amines and imines to afford high yields of cross-coupled imine products.
2,2′-Bipyridine-ligated copper complexes, in combination with TEMPO (2,2,6,6-tetramethylpiperidine-N-oxyl), are highly effective catalysts for aerobic alcohol oxidation. Considerable uncertainty and ...debate exist over the mechanism of alcohol oxidation mediated by CuII and TEMPO. Here, we report experimental and density functional theory (DFT) computational studies that distinguish among numerous previously proposed mechanistic pathways. Oxidation of various classes of radical-probe substrates shows that long-lived radicals are not formed in the reaction. DFT computational studies support this conclusion. A bimolecular pathway involving hydrogen-atom-transfer from a CuII–alkoxide to a nitroxyl radical is higher in energy than hydrogen transfer from a CuII–alkoxide to a coordinated nitroxyl species. The data presented here reconcile a collection of diverse and seemingly contradictory experimental and computational data reported previously in the literature. The resulting Oppenauer-like reaction pathway further explains experimental trends in the relative reactivity of different classes of alcohols (benzylic versus aliphatic and primary versus secondary), as well as the different reactivity observed between TEMPO and bicyclic nitroxyls, such as ABNO (ABNO = 9-azabicyclo3.3.1nonane N-oxyl).
Manganese oxides are a highly promising class of water-oxidation catalysts (WOCs), but the optimal MnO x formulation or polymorph is not clear from previous reports in the literature. A complication ...not limited to MnO x -based WOCs is that such catalysts are routinely evaluated by different methods, ranging from the use of a chemical oxidant such as Ce4+, photoactive mediators such as Ru(bpy)32+, or electrochemical techniques. Here, we report a systematic study of nine crystalline MnO x materials as WOCs and show that the identity of the “best” catalyst changes, depending on the oxidation method used to probe the catalytic activity.
Objective: To provide an overview for practicing clinicians on the pharmacological basis of cardiometabolic risk induced by antipsychotic drugs in patients with serious mental illness, to propose ...hypotheses to explain these risks and to give tips for managing cardiometabolic risk during antipsychotic treatment.
Method: A MEDLINE search using terms for atypical antipsychotics (including individual drug names), metabolic, cardiovascular, weight gain and insulin resistance, cross‐referenced with schizophrenia was performed on articles published between 1990 and May 2008.
Results: Strong evidence exists for significant cardiometabolic risk differences among several antipsychotic agents. Histamine H1 and serotonin 5HT2C antagonism are associated with risk of weight gain, but receptor targets for dyslipidemia and insulin resistance have not yet been identified. Convincing data indicate that hypertriglyceridemia and insulin resistance may occur in the absence of weight gain with certain antipsychotics.
Conclusion: Although lifestyle and genetics may contribute independent risks of cardiometabolic dysfunction in schizophrenia and other serious mental illness, antipsychotic treatment also represents an important contributor to risk of cardiometabolic dysfunction, particularly for certain drugs and for vulnerable patients. Mental health professionals must learn to recognize the clinical signposts indicating antipsychotic‐related cardiometabolic problems to forestall progression to type II diabetes, cardiovascular events and premature death.
Recent studies have highlighted the ability of CuII to catalyze the aerobic oxidative functionalization of C−H bonds; however, very little is known about the mechanisms of these reactions. Here, we ...describe the CuII-catalyzed C−H methoxylation and amidation of a macrocylic arene substrate with O2 as the stoichiometric oxidant. Kinetic and in situ spectroscopic studies demonstrate the involvement of three different oxidation states of Cu in the catalytic mechanism, including an aryl-CuIII intermediate. These observations establish a novel mechanistic pathway that has implications for numerous other Cu-catalyzed aerobic oxidation reactions.
Electrochemical studies of the reduction and oxidation reactions of five different organic nitroxyls have been performed across a wide pH range (0–13). The resulting Pourbaix diagrams illustrate ...structural effects on their various redox potentials and on the pK a values of the corresponding hydroxylamine and hydroxylammonium ions. Evidence is also given for the reversible formation of a hydroxylamine N-oxide when nitroxyls are oxidized in alkaline media. Structural effects on the thermodynamics of this reaction are assessed.
Cooperative catalysis between CuII and redox-active organic cocatalysts is a key feature of important chemical and enzymatic aerobic oxidation reactions, such as alcohol oxidation mediated by ...Cu/TEMPO and galactose oxidase. Nearly 20 years ago, Markó and co-workers reported that azodicarboxylates, such as di-tert-butyl azodicarboxylate (DBAD), are effective redox-active cocatalysts in Cu-catalyzed aerobic alcohol oxidation reactions Markó I. E. , et al. Science 1996, 274, 2044 , but the nature of the cooperativity between Cu and azodicarboxylates is not well understood. Here, we report a mechanistic study of Cu/DBAD-catalyzed aerobic alcohol oxidation. In situ infrared spectroscopic studies reveal a burst of product formation prior to steady-state catalysis, and gas-uptake measurements show that no O2 is consumed during the burst. Kinetic studies reveal that the anaerobic burst and steady-state turnover have different rate laws. The steady-state rate does not depend on O2 or DBAD. These results, together with other EPR and in situ IR spectroscopic and kinetic isotope effect studies, reveal that the steady-state mechanism consists of two interdependent catalytic cycles that operate in sequence: a fast CuII/DBAD pathway, in which DBAD serves as the oxidant, and a slow CuII-only pathway, in which CuII is the oxidant. This study provides significant insight into the redox cooperativity, or lack thereof, between Cu and redox-active organic cocatalysts in aerobic oxidation reactions.
Homogeneous Pd catalysts have been identified for the conversion of cyclohexenone and tetralone O-pivaloyl oximes to the corresponding primary anilines and 1-aminonaphthalenes. This method is ...inspired by the Semmler–Wolff reaction, a classic method that exhibits limited synthetic utility owing to its forcing conditions, narrow scope, and low product yields. The oxime N–O bond undergoes oxidative addition to Pd0(PCy3)2, and the product of this step has been characterized by X-ray crystallography and shown to undergo dehydrogenation to afford the aniline product.
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