Synthesis of γ-, δ-, and ε-Lactams by Asymmetric Transfer Hydrogenation of N-(tert-Butylsulfinyl)iminoesters

Highly enantiomerically enriched γ- and δ-lactams have been prepared by a simple and very efficient procedure that involves the asymmetric transfer hydrogenation of N-(tert-butylsulfinyl)iminoesters followed by desulfinylation of the nitrogen atom and spontaneous cyclization to the desired lactams during the basic workup procedure. Five- and six-membered ring lactams bearing aromatic, heteroaromatic, and aliphatic substituents have been obtained in very high yields and ee’s up to >99%. A slight modification of the procedure also allowed the preparation of ε-lactams in good yields and very high enantioselectivities. Both enantiomers of the final lactams could be prepared with equal efficiency by changing the absolute configuration of the sulfinyl chiral auxiliary.

Synthesis of Nitrogenated Heterocycles by Asymmetric Transfer Hydrogenation of N-(tert-Butylsulfinyl)haloimines

Highly optically enriched, protected, nitrogenated heterocycles with different ring sizes have been synthesized by a very efficient methodology consisting of the asymmetric transfer hydrogenation of N-(tert-butylsulfinyl)haloimines followed by treatment with a base to promote an intramolecular nucleophilic substitution process. N-Protected aziridines, pyrrolidines, piperidines, and azepanes bearing aromatic, heteroaromatic, and aliphatic substituents have been obtained in very high yields and diastereomeric ratios up to >99:1. The free heterocycles can be easily obtained by a simple and mild desulfinylation procedure. Both enantiomers of the free heterocycles can be prepared with the same good results by changing the absolute configuration of the sulfur atom of the sulfinyl group.

Environmentally friendly and regioselective C3-alkylation of indoles with alcohols through a hydrogen autotransfer strategy

The direct alkylation of indoles using KOH and alcohols, as initial source of the electrophile, under solvent-free conditions is a safe and environmentally benign strategy for selective modification of these structures at the C3-position, without using hazardous and difficult to handle bromide or iodide derivatives or toxic and expensive transition metal catalysts. The protocol shows a broad scope, including halogenated indoles and secondary alcohols.

Copper-Catalyzed Asymmetric Alkylation of β-Keto Esters with Xanthydrols

The copper(II) triflate-tert-butyl-bisoxazoline [Cu(OTf)2-t-Bu-BOX]-catalyzed asymmetric alkylation of β-keto esters using free benzylic alcohols such as xanthydrols, as alkylating agents, is herein described for the first time. This green protocol renders in general the corresponding products with good results in terms of both yields and enantioselectivities using different keto esters, even when quaternary stereocenters were created. The scope, limitations and mechanistic aspects of the process are also discussed.

Direct Nucleophilic Substitution of Free Allylic Alcohols in Water Catalyzed by FeCl3⋅6 H2O: Which is the Real Catalyst?

The allylic substitution reaction, and particularly the direct allylic amination reaction, of free allylic alcohols in water catalyzed by FeCl3⋅6 H2O is described. This novel environmentally-friendly methodology allows the use of a wide variety of nitrogenated nucleophiles such as sulfonamides, carbamates, benzamides, anilines, benzotriazoles, and azides, generally giving good yields of the corresponding substitution products. The synthetic applicability of the process is also demonstrated because the reaction can be performed on gram-scale. Additionally, carbon nucleophiles such as silylated nucleophiles, aromatic compounds, and malonates also proved to be suitable for this transformation. Finally, the nature of the catalytic species present in aqueous media is unveiled, pointing towards the formation of hexaaquo iron(III) complexes.

Synthesis of Dihydroisobenzofurans via Palladium-Catalyzed Sequential Alkynylation/Annulation of 2-Bromobenzyl and 2-Chlorobenzyl Alcohols under Microwave Irradiation

The palladium-catalyzed synthesis of dihydroisobenzofurans has been performed by sequential Sonogashira cross-coupling/cyclization reactions between terminal alkynes and 2-(hydroxymethyl)bromo- and chlorobenzenes in methanol as solvent at 130 °C under microwave irradiation. A 4,4′-dichlorobenzophenone oxime-derived chloro-bridged palladacycle is an efficient pre-catalyst to perform this tandem process using 2-dicyclohexylphosphanyl-2′,4′,6′-triisopropylbiphenyl (Xphos) as ancillary ligand and potassium hydroxide as base in the absence of a copper cocatalyst. Under these conditions, functionalized 2-bromo- and 2-chlorobenzaldehydes are also suitable partners in the domino process affording phthalans in good yields. All the reactions can be performed under air and employing reagent-grade chemicals under low loading conditions (1 mol% Pd).

Bis(2-aminobenzoimidazole)-Organocatalyzed Asymmetric Alkylation of Activated Methylene Compounds with Benzylic and Allylic Alcohols

The first organocatalyzed asymmetric alkylation of activated methylene compounds using benzylic and allylic alcohols as alkylating agents through dual hydrogen bond activation in an SN1-type reaction is reported. This green protocol employs a bis(2-aminobenzoimidazole) in combination with an achiral Brønsted acid as a bifunctional catalytic system and gives the alkylation products with moderate to good enantioselectivities. Although the scope of the reaction is limited, this methodology can be considered as complementary to existing metal-catalyzed processes. In addition, modest results were obtained in a first attempt to perform a metal-free asymmetric Tsuji–Trost reaction using allylic alcohols. Finally, the recovery and reusability of the organocatalyst is also achieved.

Microwave-Enhanced Asymmetric Transfer Hydrogenation of N-(tert-Butylsulfinyl)imines

Microwave irradiation has considerably enhanced the efficiency of the asymmetric transfer hydrogenation of N-(tert-butylsulfinyl)imines in isopropyl alcohol catalyzed by a ruthenium complex bearing the achiral ligand 2-amino-2-methylpropan-1-ol. In addition to shortening reaction times for the transfer hydrogenation processes to only 30 min, the amounts of ruthenium catalyst and isopropyl alcohol can be considerably reduced in comparison with our previous procedure assisted by conventional heating, which diminishes the environmental impact of this new protocol. This methodology can be applied to aromatic, heteroaromatic and aliphatic N-(tert-butylsulfinyl)ketimines, leading, after desulfinylation, to the expected primary amines in excellent yields and with enantiomeric excesses of up to 96 %.

Ultrasound-assisted selective hydrogenation of C-5 acetylene alcohols with Lindlar catalysts

The selective hydrogenation of 2-methyl-3-butyn-2-ol (MBY) was performed in the presence of Lindlar catalyst, comparing conventional stirring with sonication at different frequencies of 40, 380 and 850 kHz. Under conventional stirring, the reaction rates were limited by intrinsic kinetics, while in the case of sonication, the reaction rates were 50–90% slower. However, the apparent reaction rates were found to be significantly frequency dependent with the highest rate observed at 40 kHz. The original and the recovered catalysts after the hydrogenation reaction were compared using bulk elemental analysis, powder X-ray diffraction and scanning and transmission electron microscopy coupled with energy-dispersive X-ray analysis. The studies showed that sonication led to the frequency-dependent fracturing of polycrystalline support particles with the highest impact caused by 40 kHz sonication, while monocrystals were undamaged. In contrast, the leaching of Pd/Pb particles did not depend on the frequency, which suggests that sonication removed only loosely-bound catalyst particles.

Mesoporous Metal Complex–Silica Aerogels for Environmentally Friendly Amination of Allylic Alcohols

Two series of mesoporous hybrid iron(III) complex–silica aerogels were prepared in one-pot synthesis by using the sol–gel coordination chemistry approach. The use of the ligands 3-(2-aminoethylamino)propyltrimethoxysilane and 2-(diphenylphosphino)ethyltriethoxysilane, both with terminal triethoxysilyl groups, were used to incorporate metal complexes in situ into the framework of silica, through their co-condensation with a silicon alkoxide during the aerogel formation. This methodology yielded optically translucent hybrid mesoporous gels with homogeneous metal incorporation and excellent textural properties. The catalytic performance of these materials was tested in the direct amination of allylic alcohols in water as a target reaction, with activities comparable or even higher than those corresponding to the homogeneous iron(III) complex. Furthermore, these catalysts were stable and maintained their catalytic activity after six reaction cycles.

Performance Assessment of a Polymer Electrolyte Membrane Electrochemical Reactor under Alkaline Conditions – A Case Study with the Electrooxidation of Alcohols

A novel polymer electrolyte membrane electrochemical reactor (PEMER) configuration has been employed for the direct electrooxidation of propargyl alcohol (PGA), a model primary alcohol, towards its carboxylic acid derivatives in alkaline medium. The PEMER configuration comprised of an anode and cathode based on nanoparticulate Ni and Pt electrocatalysts, respectively, supported on carbonaceous substrates. The electrooxidation of PGA was performed in 1.0 M NaOH, where a cathode based on a gas diffusion electrode was manufactured for the reduction of oxygen in alkaline conditions. The performance of a novel alkaline anion-exchange membrane based on Chitosan (CS) and Poly(vinyl) alcohol (PVA) in a 50:50 composition ratio doped with a 5 wt.% of poly (4-vinylpyridine) organic ionomer cross-linked, methyl chloride quaternary salt resin (4VP) was assessed as solid polymer electrolyte. The influence of 4VP anionic ionomer loading of 7, 12 and 20 wt.% incorporated into the electrocatalytic layers was examined by SEM and cyclic voltammetry (CV) upon the optimisation of the electroactive area, the mechanical stability and cohesion of the catalytic ink onto the carbonaceous substrate for both electrodes. The performance of the 4VP/CS:PVA membrane was compared with the commercial alkaline anion-exchange membrane FAA −a membrane generally used in direct alcohol alkaline fuel cells- in terms of polarisation plots in alkaline conditions. Furthermore, preparative electrolyses of the electrooxidation of PGA was performed under alkaline conditions of 1 M NaOH at constant current density of 20 mA cm−2 using a PEMER configuration to provide proof of the principle of the feasibility of the electrooxidation of other alcohols in alkaline media. PGA conversion to Z isomers of 3-(2-propynoxy)-2-propenoic acid (Z-PPA) was circa 0.77, with average current efficiency of 0.32. Alkaline stability of the membranes within the PEMER configuration was finally evaluated after the electrooxidation of PGA.

TERT promoter mutations in pancreatic endocrine tumours are rare and mainly found in tumours from patients with hereditary syndromes

One of the hallmarks of cancer is its unlimited replicative potential that needs a compensatory mechanism for the consequential telomere erosion. Telomerase promoter (TERTp) mutations were recently reported as a novel mechanism for telomerase re-activation/expression in order to maintain telomere length. Pancreatic endocrine tumors (PETs) were so far recognized to rely mainly on the alternative lengthening of telomeres (ALT) mechanism. It was our objective to study if TERTp mutations were present in pancreatic endocrine tumors (PET) and could represent an alternative mechanism to ALT. TERTp mutations were detected in 7% of the cases studied and were mainly associated to patients harbouring hereditary syndromes. In vitro, using PET-derived cell lines and by luciferase reporter assay, these mutations confer a 2 to 4-fold increase in telomerase transcription activity. These novel alterations are able to recruit ETS transcription factor members, in particular GABP-α and ETV1, to the newly generated binding sites. We report for the first time TERTp mutations in PETs and PET-derived cell lines. Additionally, our data indicate that these mutations serve as an alternative mechanism and in an exclusive manner to ALT, in particular in patients with hereditary syndromes.

Grundzüge der methodik des katechetischen religionsunterrichtes in evangelischen volksschulen, durch fremde und eigne beispiele, wie auch aufgaben erlaütert [!]

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The specific heats of ethyl and propyl alcohols /

Thesis (Ph.D.)--University of California, Berkeley, 1919.