New pyridine N-oxides as chiral organocatalysts in the asymmetric allylation of aromatic aldehydes

Asymmetric allylation of aromatic aldehydes 1 with allyltrichlorosilane (2) can be catalyzed by new terpene-derived bipyridine N,N′-dioxides 12-15 and an axially chiral biisoquinoline dioxide 17b with good enantioselectivities. Dioxides have been found to be more reactive catalysts than their monooxide counterparts.     

Chiral Lewis base promoted trichlorosilane reduction of ketimines. An enantioselective organocatalytic synthesis of chiral amines

The reduction of the carbon-nitrogen double bond is an important transformation. Here we report our studies on a family of chiral organic catalysts able to promote the stereoselective reduction of ketimines with trichlorosilane. The very cheap, metal-free catalysts were easily prepared in one step from commercially available products, namely a chiral aminoalcohol and picolinic acid derivatives. The catalyst structure was extensively modified in a study that allowed to identify an extremely active species, able to promote the reduction on a large variety of substrates with high efficiency (up to 95% ee). A three component methodology has been also developed, where the enantiomerically enriched amine was isolated after performing the reaction by mixing a ketone and an amine in the presence of trichlorosilane and the catalyst. Its synthetic potentiality was demonstrated by employing the present metal-free catalytic procedure in the preparation of (S)-metolachlor, a potent and widely used herbicide.     

A novel method for the reduction of sulfoxides and pyridine N-oxides with the system silane/MoO2Cl2

A novel method for the reduction of sulfoxides and pyridine N-oxides using a silane and a catalytic amount of MoO₂Cl₂ in excellent yields and with a wide functional group tolerance is reported. A green protocol for this reaction was developed in water with the air-stable catalytic system PMHS/MoO₂Cl₂(H₂O)₂.     

Synthesis and reactions of 3-halomethyl-substituted oxazine N-oxides

A series of 3-halomethyl-5,6-dihydro-1,2-oxazine N-oxides (halogen = Cl, Br, I) is prepared from 4-phenyl-3,6,6-trimethyl-5,6-dihydro-4H-oxazine N-oxide by means of a silylation/halogenation sequence. The obtained halogenated N-oxides undergo reactions typical of cyclic six-membered nitronates including 1,3-dipolar cycloaddition, addition of nucleophiles, and substitution of the halogen by C-, S-, and N-nucleophiles.     

Mild addition of carbon nucleophiles to pyridine and quinoline N-oxides under different activation conditions

In the course of our syntheses of functionalised pyridine and quinoline derivatives, we examined the reactivities of pyridine and quinoline N-oxides towards the nucleophilic addition of acidic carbon derivatives. Different activating reagents were used, such as PyBroP, triflic anhydride and a combination of pyrrolidine phosphoramide and triflic anhydride.     

Cu(I)-mediated deoxygenation of N-oxides to amines

A mild and highly efficient deoxygenation of variety of N-oxides using an inexpensive CuX, or a CuX-Zn or CuX-Al couple is described.     

Sulfonium ylides derived from 2-hydroxy-benzoquinones: crystal and molecular structure and their one-step conversion into Mannich bases by amine N-oxides

Reaction of 2-hydroxy-para-benzoquinones with DMSO/Ac₂O produced dimethylsulfonium ylides, of which crystal structures as well as solid and liquid state NMR spectra were recorded. The ylides react with tertiary methylamine N-oxides in a one-pot, multi-step process to 3-methylamino-substituted benzoquinones. The mechanism starts with a deoxygenative deprotonation of the amine N-oxides, followed by a formal electrophilic displacement of DMSO by the resulting carbonium-iminium ion.     

Synthesis of 3-substituted-4-hydroxyquinoline N-oxides from the Baylis-Hillman adducts of o-nitrobenzaldehydes

The reaction of the Baylis-Hillman adducts 1b-f derived from o-nitrobenzaldehydes in trifluoroacetic acid in the presence of triflic acid (0.2 equiv.) afforded 3-substituted-4-hydroxyquinoline N-oxides 2b-e and 2a in good to moderate yields. The reaction mechanism was evidenced by the experiment with 1f, the Baylis-Hillman adduct of 2-nitrobenzaldehyde N-tosylimine, as the one involving N-hydroxyisoxazoline as the key intermediate.     

A novel reagent combination for the oxidation of highly electron deficient pyridines to N-oxides: trifluoromethanesulfonic anhydride/sodium percarbonate

A novel reagent combination, Tf₂O/Na₂CO₃·1.5H₂O₂, has been developed for the oxidation of highly electron deficient pyridines to their corresponding N-oxides. The N-oxidation reaction, utilizing the in situ generated peracid, proceeds under mild conditions that allow for a number of functional groups and substitution patterns on the pyridine ring.     

A general method for the deoxygenation of aromatic N-oxides using RuCl3·xH2O

An efficient, simple and selective method for the deoxygenation of aromatic N-oxides, such as N-arylnitrones, azoxybenzenes, N-heteroarene N-oxides using ruthenium(III) chloride to afford deoxygenated products in excellent yields, is described.     

Copper powder-catalyzed N-arylation of imidazoles in water using 2-(hydrazinecarbonyl)pyridine N-oxides as the new ligands

2-(2-Hydrazinecarbonyl)pyridine N-oxides, which were derived from pyrrole-2-carbohydrazides and pyridine N-oxides, were synthesized and utilized as the ligands for copper powder-catalyzed N-arylation of imidazoles with aryl halides in water. Imidazoles could be arylated smoothly with various aryl halides to provide the title products in preferable yields without the need of an inert atmosphere.     

Enantioselective aldol reactions of trichlorosilyl enol ethers catalyzed by chiral N,N-dioxides and monodentate N-oxides

Chiral N,N^′-dioxides and monodentate N-oxides were employed as catalysts in catalytic, enantioselective aldol reactions of trichlorosilyl enol ethers. The reactions of acyclic enol ethers using N,N^′-dioxides resulted in the anti-adducts from (E)-enol ethers and the syn-adducts from (Z)-enol ethers. The reactions of cyclic (E)-enol ethers using N,N^′-dioxides gave the anti-adducts, whereas monodentate N-oxides predominantly gave the syn-adducts.     

N-Prolinylanthranilic acid derivatives as bifunctional organocatalysts for asymmetric aldol reactions

Several N-prolinylanthranilic acid derivatives were prepared and tested as bifunctional organocatalysts in the direct asymmetric aldol reaction of cyclohexanone with p-nitrobenzaldehyde. It was found that methyl substitution ortho to the carboxylic acid improves enantioselectivity, but substitution ortho to the anilide group does not. The catalyst derived from 2-amino-6-methylbenzoic acid was tested over a range of direct asymmetric aldol reactions and its overall performance is equal to or better than many of the known prolinamide catalysts in terms of yield, diastereoselectivity, and enantioselectivity.     

Simple pyridylmethylamines: efficient and robust N,N-ligands for Suzuki-Miyaura coupling reactions

A series of pyridylmethylamines have been synthesized in one step from commercially available starting material and identified as effective ligands for Pd-catalyzed carbon-carbon bond formation through Suzuki-Miyaura coupling reaction. The N,N-pyridylmethylamine-Pd catalytic systems appeared as an interesting and robust compromise between catalytic efficiency, substrate compatibility, and practical aspects.     

On the non-classical course of Polonowski reactions of N-benzylmorpholine-N-oxide (NBnMO)

The Polonowski reaction of NBnMO (4) afforded tropone (10) and the novel isoindole 11 besides the expected products benzaldehyde and acetmorpholide, in a temperature-dependent ratio. The reaction proceeded via two primary carbenium-iminium ion intermediates, an exo-centered species 5 which underwent a benzylium-tropylium type rearrangement, and a ring-centered species 6, which reacted further to isoindole 11 by intramolecular electrophilic substitution. The experimental findings were in good agreement with DFT computational data.     

Enantioselective cyanosilylation of ketones catalyzed by double-activation catalysts with N-oxides

Enantioselective addition of trimethylsilyl cyanide to ketones by a catalytic double-activation method is described. By combinatorially using 2.0 mol% of a chiral salen-titanium complex and 1.0 mol% of an achiral tertiary amine N-oxide, aromatic, aliphatic and α,β-unsaturated ketones are converted into corresponding cyanohydrin trimethylsilyl ethers with 50-93% yield and 59-86% ee. The effects of ligand structure, catalyst loading and substrate concentration, solvents, the nature of Lewis base, counter ion and other additives, temperature, and substrate structure on the enantioselectivity are discussed. Three possible paths to achieve the asymmetric version of double-activation catalysis and two independent examples of it are proposed.     

Chiral N-phosphonyl imine chemistry: new reagents and their applications for asymmetric reactions

Novel chiral N-phosphonyl imines 2 have been designed and synthesized using chiral N-phosphoramide 1. These N-phosphonyl imines have been successfully utilized for asymmetric aza-Darzens reaction and asymmetric aza-Henry reaction. The C₂-symmetric chiral auxiliary tolerates oxidation, is not sensitive to racemization and can be recycled for large scale synthesis.     

N,N′-Diisopropyl- and N,N′-dicyclohexylthiourea cadmium(II) complexes as precursors for the synthesis of CdS nanoparticles

Crystals of the cadmium(II) complexes of N,N-diisopropylthiourea and N,N-dicyclohexylthiourea were obtained and their X-ray single crystal structures determined. These complexes are air-stable, easy to prepare and inexpensive and decompose cleanly to give good quality crystalline CdS. The nanoparticles of CdS thus obtained showed quantum confinement effects in their optical spectra, with close to band-edge emission in luminescence experiments. The broad diffraction patterns observed are typical of nanodimensional particles. The variation of concentration of precursor-to-HDA ratio change the isolated materials from spheres to rod-shaped. TEM images showed agglomerates of needle-like plate of particles.     

Solid-phase synthesis of benzimidazole N-oxides on SynPhase™ Lanterns

A solid-phase synthesis of benzimidazole N-oxides was developed while attempting to synthesize 1,5-benzodiazepine-2,4-diones. The key step of the synthesis involves the reduction of an arylnitro to a hydroxyamino intermediate which subsequently condenses with an internal carbonyl group to give a benzimidazole N-oxide. A library of nine benzimidazole N-oxides was prepared on SynPhase™ Lanterns using this reduction-cyclization methodology.     

(N-Arylaminomethyl)pyridine-N-oxides: Synthesis and characterization of potential ligand systems and the formation of their N,O-chelate aluminum complexes

Pyridine-N-oxide-2-carbaldehyde (4a) was converted to the corresponding imine (5a) by treatment with 2,6-diisopropylaniline. Subsequent reduction with a sodium borohydride gave the corresponding (N-arylaminomethyl)pyridine-N-oxide derivative (6a). A series of analogous compounds was prepared starting from the respective (aldimino)quinoline-N-oxide (4b) or (ketimino)pyridine-N-oxide (10) systems. Deprotonation of the (aminomethyl)pyridine-N-oxides resulted in a series of unexpected reactions, such as coupling, internal redox reactions or fragmentation. Eventually, the N,O-chelate aluminum complexes (22, 23) derived from the (aminoethyl)pyridine-N-oxide ligand systems could be obtained by treatment of the respective iminopyridine-N-oxides with trimethylaluminum. Many products were characterized by X-ray diffraction.