Chiral pyridine N-oxides derived from monoterpenes as organocatalysts for stereoselective reactions with allyltrichlorosilane and tetrachlorosilane

The synthesis of enantiomerically pure C₂-symmetric dipyridylmethane ligands and related N,N′-dioxides is reported. A procedure for the synthesis of a few new enantiomerically pure C₂-symmetric pyridine N-oxides and the preparation of four pyridine N-oxides with oxygen and nitrogen atoms as further coordinating elements in the heterocycle framework is described. All compounds were prepared from naturally occurring monoterpenes. These new compounds were assessed as organocatalysts in two different reactions, namely the allylation of aldehydes with allyltrichlorosilane that afforded homoallylic alcohols in good yields and up to 85% ee and the stilbene oxide opening by the addition of tetrachlorosilane that gave chlorohydrin in quantitative yield and up to 70% ee.     

‘Reductive ozonolysis’ via a new fragmentation of carbonyl oxides

This account describes the development of methodologies for ‘reductive’ ozonolysis, the direct ozonolytic conversion of alkenes into carbonyl groups without the intermediacy of 1,2,4-trioxolanes (ozonides). Ozonolysis of alkenes in the presence of DMSO produces a mixture of aldehyde and ozonide. The combination of DMSO and Et₃N results in improved yields of carbonyls but still leaves unacceptable levels of residual ozonides; similar results are obtained using secondary or tertiary amines in the absence of DMSO. The influence of amines is believed to result from conversion to the corresponding N-oxides; ozonolysis in the presence of amine N-oxides efficiently suppresses ozonide formation, generating high yields of aldehydes. The reactions with amine oxides are hypothesized to involve an unprecedented trapping of carbonyl oxides to generate a zwitterionic adduct, which fragments to produce the desired carbonyl group, an amine, and ¹O₂.     

Investigation of Symphytum cordatum alkaloids by liquid-liquid partitioning, thin-layer chromatography and liquid chromatography-ion-trap mass spectrometry

From the alkalised crude extract of Symphytum cordatum (L.) W.K. roots, pyrrolizidine alkaloids (PAs) were extracted as free tertiary bases and polar N-oxides in a merely one-step liquid-liquid partitioning (LLP) in separation funnel and subsequently pre-fractionated by preparative multiple-development (MD) thin-layer chromatography (TLC) on silica gel plates. In this way three alkaloid fractions of different polarities and retention on silica gel plates were obtained as: the most polar N-oxides of the highest retention, the tertiary bases of medium retention, and diesterified N-oxides of the lowest retention. The former fraction was reduced into free bases by sodium hydrosulfite and purified by LLP on Extrelut-NT3 cartridge. It was further analysed together with the two other fractions by high-performance liquid chromatography (HPLC)-ion-trap mass spectrometry with atmospheric pressure chemical ionization (APCI) interface on XTerra C₁₈ column using a gradient elution. Based on MSⁿ spectra, 18 various alkaloids have been tentatively determined for the first time in this plant as the following types of structure: echimidine-N-oxide (three diasteroisomers), 7-sarracinyl-9-viridiflorylretronecine (two diasteroisomers), echimidine (two diasteroisomers), lycopsamine (two diasteroisomers), dihydroechinatine-N-oxide, dihydroheliospathuline-N-oxide, lycopsamine-N-oxide (three diasteroisomers), 7-acetyllycopsamine-N-oxide, symphytine-N-oxide (two diasteroisomers) and 2″,3″-epoxyechiumine-N-oxide.     

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.     

One-pot N-dealkylation and acid-catalyzed rearrangement of morphinans into aporphines

The one-pot N-demethylation and acid-catalyzed rearrangement of morphinan-N-oxides offers a new, shorter and more efficient route to neuropharmacologically important N-substituted aporphines. An improved procedure is described for the preparation of the starting alkaloid N-oxides using Na₂WO₄ as catalyst. The transetherification during the rearrangement of codeinone into 2-O-alkyl-norapocodeines is documented.     

Access to lincomycin N-oxide isomers controlled by reaction conditions

Oxidation of lincomycin with H₂O₂ in alkaline media leads to N-oxides, besides the conversion of thiomethyl group into sulfoxides and sulfones. NH₄OH favors formation of the S-isomer; both R- and S-isomers of the N-oxide are formed in the presence of NaOH. Addition of acetonitrile markedly accelerates the reaction.     

Transition-metal-free approach to synthesis of indolines from N-(ortho-chloromethyl)aryl amides and iodonium ylides

A transition-metal-free method for the synthesis of indolines has been developed. In the presence of K₂CO₃, the cyclization reaction of N-(ortho-chloromethyl)aryl amides and iodonium ylides proceeded smoothly at room temperature in moderate to good yields.     

Evidence for a single minimum potential for hydrogen bonds of pyridine N-oxide complexes with dichloroacetic acid in dichloromethane

FTIR spectra of dichloracetic acid and its eight complexes with substituted pyridine N-oxides and N,N-dimethylaniline in dichloromethane-d₂ are reported. 4-N,N-dimethylaminopyridine N-oxides form two types of complexes with dichloroacetic acid; the acid interacts with NO or Me₂N groups. The shape of the second derivative of absorption in the carbonyl region implies that the hydrogen bonds are described by a strongly asymmetrical quasi-single minimum potential. The situation with regard to the observed carbonyl frequencies as related to conformational equilibria is reviewed.     

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.     

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.     

3-Halomethylated cyclic nitronates: synthesis and nucleophilic substitution

A method for the introduction of a halogen atom into the methyl group attached to the C-3 atom of five- and six-membered cyclic nitronates (isoxazoline N-oxides and oxazine N-oxides, respectively) has been studied. The process involves silylation of starting 3-methyl-substituted cyclic nitronates followed by halogenation of the resulting N-(silyloxy)enamines. While five- and six-membered cyclic enamines behave similarly toward elemental bromine and iodine, their reactions with NBS give different products, that were rationalized by stereoelectronic effects. The obtained halogenated nitronates were coupled with various nucleophiles affording new nitronates functionalized at the C-3 position.     

Photocatalytic deoxygenation of N–O bonds with rhenium complexes: from the reduction of nitrous oxide to pyridine N-oxides

The accumulation of nitrogen oxides in the environment calls for new pathways to interconvert the various oxidation states of nitrogen, and especially their reduction. However, the large spectrum of reduction potentials covered by nitrogen oxides makes it difficult to find general systems capable of efficiently reducing various N-oxides. Here, photocatalysis unlocks high energy species able both to circumvent the inherent low reactivity of the greenhouse gas and oxidant N₂O (E⁰(N₂O/N₂) = +1.77 V vs. SHE), and to reduce pyridine N-oxides (E_1/2(pyridine N-oxide/pyridine) = −1.04 V vs. SHE). The rhenium complex [Re(4,4′-tBu-bpy)(CO)₃Cl] proved to be efficient in performing both reactions under ambient conditions, enabling the deoxygenation of N₂O as well as synthetically relevant and functionalized pyridine N-oxides.

A rhenium-based photocatalyst enables the deoxygenation of several compounds containing N–O bonds, such as N₂O and pyridine N-oxides.     

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.     

Probing the metal complexing ability of bis-quinolizidine N-oxides: Synthesis, spectroscopy and crystal structures

New ZnX₂ (X = Cl, Br) complexes with sparteine N1-oxide, sparteine epi-N16-oxide, lupanine (2-oxosparteine) N-oxide and α-isosparteine N-oxide were obtained and characterized by spectroscopic and crystallographic methods. Complexation with N1-oxides involves inversion of the configuration at the N16 atom of sparteine, converting its C ring from a boat into a chair form, whereas the structure of sparteine epi-N16-oxide, typified by the trans boat/chair C/D quinolizidine moiety, remains unchanged upon complexation. Coordination of zinc salts in the above compounds is realized solely through the oxygen atom of the N-O group and is accompanied by protonation of the “not-N-oxide” nitrogen atom. At variance lupanine N-oxide forms bis-monodentate complexes with ZnX₂ utilizing both the N-oxide and the lactam carbonyl oxygen atoms to bridge the neighboring ZnX₂ units, while reaction of α-isosparteine N-oxide with ZnX₂ leads to formation of complex salts of the general formula [H(−)α-Sp(N-oxide)][(ZnX₃)(H₂O)].     

Reactions of 1,1,1-trihalo-3-nitrobut-2-enes with enamines derived from cycloalkanones. Rearrangement of trifluoromethylated 1,2-oxazine N-oxide into 1-pyrroline N-oxides and stereochemistry of the products

1,2-Oxazine N-oxides derived from (E)-1,1,1-trifluoro-3-nitrobut-2-ene and cyclohexanone enamines underwent spontaneous rearrangement with ring contraction to give 1-pyrroline N-oxides. Reactions of (E)-1,1,1-trifluoro(trichloro)-3-nitrobut-2-enes with N-cyclopent-enylmorpholine resulted in a series of novel CX₃-containing nitroalkyl enamines and g-nitro ketones; the stereochemistry of the synthesized compounds were studied by NMR spectroscopy and X-ray diffraction.     

KMnO4-mediated direct C2-selective C−H arylation of quinoline N-oxides with aromatic hydrazines

An efficient protocol for the synthesis of 2-arylquinoline N-oxides has been developed via KMnO₄-mediated cross-coupling reaction of quinoline N-oxides with aromatic hydrazines in moderated to good yields. The reactions proceeded efficiently over a broad range of substrates with excellent regioselectivity and functional group tolerance.     

Solvent-controlled selective synthesis of a trans-configured benzimidazoline-2-ylidene palladium(II) complex and investigations of its Heck-type catalytic activity

Reaction of N,N′-dimethylbenzimidazolyl iodide (A) with Pd(OAc)₂ in DMSO gives selectively trans-bis(N,N′-dimethylbenzimidazoline-2-ylidene) palladium(II) diiodide (trans-2) in 77% yield. The selective formation of the trans-coordination isomer and thus the cis-trans rearrangement is driven by the insolubility of trans-2 in DMSO. X-ray single-crystal diffraction analysis and ¹³C NMR spectroscopy confirm the trans-geometry of the square planar Pd(II) complex. Catalytic studies show that cis-1 and trans-2 are highly efficient in the Mizoroki-Heck coupling reaction of aryl bromides and activated aryl chlorides both in DMF and [N(n-C₄H₉)₄]Br as ionic liquid. The catalytic activities of Pd(II) complexes with N-heterocyclic carbene ligands derived from benzimidazole are comparable to their imidazole-derived analogues.     

(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.     

Study on the reactions of fluoroalkanesulfonyl azides with pyrazine and its derivatives

The thermal reactions of fluoroalkanesulfonyl azides R_fSO₂N₃ with pyrazine and its derivatives are studied in detail. All the reactions involved the fluoroalkanesulfonyl nitrene intermediates R_fSO₃N: which was captured by pyrazine to give the pyrazinium N-fluoroalkanesulfonyl ylides C₄NH₄N⁺-⁻NSO₂R_f and hydrogen abstraction product R_fSO₂NH₂, but no corresponding N-pyrazinyl fluoroalkanesulfonyl amide derivatives R_fSO₂NHC₄N₂H₃ were isolated. Excess azides did not afford the bisN-ylide product R_fSO₂N⁻-⁺NC₄H₄N⁺-⁻NSO₂R_f.     

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.