Jason G. Taylor

Stereoselective synthesis of unsymmetrical β,β-diarylacrylates by a Heck-Matsuda reaction: versatile building blocks for asymmetric synthesis of β,β-diphenylpropanoates, 3-aryl-indole, and 4-aryl-3,4-dihydro-quinolin-2-one and formal synthesis of (-)-indatraline.

β,β-Disubstituted α,β-unsaturated esters may serve as valuable derivatives for the preparation of other highly functionalized systems found in many natural products and marketed drugs. The stereoselective synthesis of unsymmetrical β,β-diarylacrylate compounds possessing two similar aromatic groups remains a substantial challenge. A simple and convenient stereoselective protocol for the preparation of β,β-disubstituted acrylates via a Heck-Matsuda reaction is reported. Good to high yields were accomplished by a ligand-free Pd-catalyzed arylation reaction of cinnamate esters with arenediazonium tetrafluoroborates. Both electron-deficient and electron-rich arenediazonium salts could be employed as arylating reagents, and cinnamate esters were generally more reactive when substituted with an electron-donating group. The overall methodology is highly stereoselective, and this attribute was taken advantage of in the asymmetric Cu-catalyzed 1,4 reduction reaction to provide β,β-diarylpropanoates in high enantioselectivities. The synthesis of a 3-aryl indole and a chiral 4-aryl-2-quinolone from β,β-diarylacrylates was achieved by cyclization in the presence of a diphosphine ligated CuH catalyst. A convenient route for the asymmetric formal synthesis of the psychoactive compound (-)-Indatraline is also presented.

Changing the Landscape: A New Strategy for Estimating Large Phylogenies

In this paper we describe a new heuristic strategy designed to find optimal (parsimonious) trees for data sets with large numbers of taxa and characters. This new strategy uses an iterative searching process of branch swapping with equally weighted characters, followed by swapping with reweighted characters. This process increases the efficiency of the search because, after each round of swapping with reweighted characters, the subsequent swapping with equal weights will start from a different group (island) of trees that are only slightly, if at all, less optimal. In contrast, conventional heuristic searching with constant equal weighting can become trapped on islands of suboptimal trees. We test the new strategy against a conventional strategy and a modified conventional strategy and show that, within a given time, the new strategy finds trees that are markedly more parsimonious. We also compare our new strategy with a recent, independently developed strategy known as the Parsimony Ratchet.

Coumarins from Free ortho-Hydroxy Cinnamates by Heck-Matsuda Arylations: A Scalable Total Synthesis of (R)-Tolterodine

Free ortho-hydroxy cinnamate ester derivatives are evaluated in the synthesis of structurally diverse 4-aryl-coumarins via a tandem Heck-Matsuda cyclization reaction. Free phenolic groups were considered incompatible with such a reaction, which usually provide the corresponding diazo dyes. A concise and scalable route employing a ligand-free, Pd-catalyzed Heck-Matsuda arylation under aerobic conditions for the preparation of (R)-Tolterodine in high overall yield and ee is also presented.

Copper(II)-catalysed addition of O–H bonds to norbornene

Cu(OTf)2 is an inexpensive, air- and moisture-stable catalyst for the O-H addition of aliphatic and aromatic acids and alcohols to norbornene.

Synthesis and Anti-Trypanosoma cruzi Activity of Diaryldiazepines

Chagas disease is a so-called “neglected disease” and endemic to Latin America. Nifurtimox and benznidazole are drugs that have considerable efficacy in the treatment of the acute phase of the disease but cause many significant side effects. Furthermore, in the Chronic Phase its efficiency is reduced and their therapeutic effectiveness is dependent on the type of T. cruzi strain. For this reason, the present work aims to drive basic research towards the discovery of new chemical entities to treat Chagas disease. Differently substituted 5,7-diaryl-2,3-dihydro-1,4-diazepines were synthesized by cyclocondensation of substituted flavones with ethylenediamine and tested as anti-Trypanosoma cruzi candidates. Epimastigotes of the Y strain from T. cruzi were used in this study and the number of parasites was determined in a Neubauer chamber. The most potent diaryldiazepine that reduced epimastigote proliferation exhibited an IC50 value of 0.25 μM, which is significantly more active than benznidazole.

Determination of formaldehyde in hair creams by gas chromatography-mass spectrometry

The perfume and cosmetics industry are one of outstanding industrial sectors in Brazil. With an average annual growth of 11% over the last ten years, Brazil has achieved third place in the world ranking for consumption of cosmetics. Hair products are amongst the most consumed cosmetics and the market is growing every day. The active ingredients in hair straightening creams vary according to the product and usually include glutaraldehyde, sodium hydroxide, calcium hydroxide, formaldehyde, pyrogallol, thioglycolic acid, and others. Currently, the most widely used chemical compound in hair products to alter the protein structure of hair to affect smoothing is formaldehyde. Four international research institutions have assessed the carcinogenic potential of formaldehyde: the International Agency for Research on Cancer (IARC), the Environmental Protection Agency (EPA), the US National Toxicology Program, and the Occupational Safety and Health Association (OSHA). These studies demonstrated that exposure to formaldehyde can cause cancer of the pharynx and nasopharynx, increase the chance of pneumonia, dermatitis and induce allergic reactions (irritation of eyes, nose and throat, insomnia, chest pains, rashes, asthma attacks, among others). In 2001, the National Health Surveillance Agency (ANVISA), which is a branch of the Brazilian Ministry of Health, issued a resolution to control the use of formaldehyde, restricting it to a concentration of up to 0.2 % in cosmetics. However, the maximum (and safe) amount of formaldehyde (0.2%) permitted in cosmetic formulations is insufficient to produce straightened hair and in addition, is a health violation. Hair products for children have been identified for the presence of formaldehyde thus highlighting the importance for regulatory control in the cosmetic industry. The literature discusses somemethodologies and techniques for the analysis of formaldehyde in various samples such as blood, food samples, air, and cosmetics amongst others. Techniques such as spectrophotometry, capillary electrophoresis, and electrochemistry were used to determine formaldehyde. However, most of these techniques involve a series of tedious and labour-intensive extraction steps and they also suffer from low limits of detection (LOD) and quantification (LOQ). High performance liquid chromatography (HPLC) is the most widely applied method for the determination of formaldehyde. Gas chromatography coupled to mass spectrometry (GC-MS) is a versatile analytical technique and attempts have been made to apply GC-MS to the determination of formaldehyde with limited success. Unfortunately, the thermal instability makes direct quantification of formaldehyde by

Arylation of β,γ-unsaturated lactones by a Heck-Matsuda reaction: an unexpected route to aryldiazene butenolides and pyridazinones

The palladium catalysed coupling of aryldiazonium salts with β-γ-unsaturated lactones under basic conditions has been investigated. Both (3H)-furanone and α-angelicalactone were evaluated as substrates in the Heck Matsuda reaction but both failed to afford the desired arylated butenolides. Under basic conditions, β-γ-unsaturated lactones generate highly nucleophilic enolates that preferentially undergo azo coupling reactions with arenediazonium salts to afford aryldiazene butenolides. The electronic and steric effect of the substituents on the aryldiazonium salt in the azo coupling reaction is described. Aryldiazene-lactone derivatives were obtained in good yields from a highly facile and straightforward procedure. An aminoisomaleimide was formed from (3H)-furanone and cyclised to the corresponding pyridazinones in modest yield.

An unusual route to a quinoline 1-oxide via intramolecular addition of an enolate to an aromatic nitro group

Abstract A mixture of ethyl 4-(2-nitrophenyl)butenoates undergoes an unusual intramolecular cyclisation in the presence of a catalytic amount of potassium tert-butoxide.

Aqueous Microemulsions as Efficient and Versatile Media for Transition-Metal-Catalyzed Reactions

The search for efficient and versatile reaction medium to perform transition-metal-catalyzed reactions is a continuous challenge to the synthetic community. Organic solvents have been traditionally employed for this task, nevertheless, new environmentally friendly, safe, and economically viable alternatives are still highly sought after. In this context, herein, we present an overview of some interesting applications of aqueous microemulsions (oil-in-water, O/W) for transition metal catalyzed reactions as an alternative and promising aqueous-organic reaction medium that has been found to be a highly effective tool in overcoming some environmental or practical issues presented by traditional organic solvents.

Sub-15 nm CeO2 nanowires as an efficient non-noble metal catalyst in the room-temperature oxidation of aniline

We described herein the facile synthesis of sub-15 nm CeO2 nanowires based on a hydrothermal method without the use of any capping/stabilizing agent, in which an oriented attachment mechanism took place during the CeO2 nanowire formation. The synthesis of sub-15 nm CeO2 nanowires could be achieved on relatively large scales (∼2.6 grams of nanowires per batch), in high yields (>94%), and at low cost. To date, there are only a limited number of successful attempts towards the synthesis of CeO2 nanowires with such small diameters, and the reported protocols are typically limited to low amounts. The nanowires displayed uniform shapes and sizes, high surface areas, an increased number of oxygen defects sites, and a high proportion of Ce3+/Ce4+ surface species. These features make them promising candidates for oxidation reactions. To this end, we employed the selective oxidation of aniline as a model transformation. The sub-15 nm CeO2 nanowires catalyzed the selective synthesis of nitrosobenzene (up to 98% selectivity) from aniline at room temperature using H2O2 as the oxidant. The effect of solvent and temperature during the catalytic reaction was investigated. We found that such parameters played an important role in the control of the selectivity. The improved catalytic activities observed for the sub-15 nm nanowires could be explained by: i) the uniform morphology with a typical dimension of 11 ± 2 nm in width, which provides higher specific surface areas relative to those of conventional catalysts; ii) the significant concentration of oxygen vacancies and high proportion of Ce3+/Ce4+ species at the surface that represent highly active sites towards oxidation reactions; iii) the crystal growth along the (110) highly catalytically active crystallographic directions, and iv) the mesoporous surface which is easily accessible by liquid substrates. The results reported herein demonstrated high activities under ambient conditions, provided novel insights into selectivities, and may inspire novel metal oxide-based catalysts with desired performances.