Chiral phenylselenyl derivatives of pyrrolidine and Cinchona alkaloids: nitrogen–selenium donating ligands in palladium-catalyzed asymmetric allylic alkylation

Enantiomeric pyrrolidine alcohols and Cinchona alkaloids reacted with PhSeCN/Bu₃P in toluene at 0–25 °C to give the corresponding phenyl selenides with complete inversion of configuration at the substitution centers. Thus, the chiral selenoethers obtained were tested in the Pd-catalyzed allylic alkylation of dimethyl malonate with rac-1,3-diphenyl-2-propenyl acetate. When chiral selenium pyrrolidine derivatives were applied, the enantioselectivity observed was improved versus the respective sulfur pyrrolidine derivatives up to over 98% ee. The results suggest that the pyrrolidine selenoethers served as the effective N(sp³), Se-donating chiral ligands. The selenoethers obtained from Cinchona alkaloids also gave the allylic alkylation product with a higher ee over those for the corresponding thioethers. The results are in agreement with nucleophilic attack directed at the allylic carbon located trans to the chalcogen atom in the intermediate η³-allylpalladium complex.     

Kinetic and mechanistic studies on the oxidation of pyrrolidine by bis(hydrogenperiodato)argentate(III) complex anion

The kinetics of oxidation of pyrrolidine by bis(hydrogenperiodato)argentate(III) complex anion ([Ag(HIO₆)₂]^5?) was studied in alkaline medium, with reaction temperatures in the range of 15.0–30.0 °C. The experiments indicated that the oxidation follows an overall second-order reaction, being first-order in both Ag(III) and pyrrolidine. The observed second-order rate constants, k′, decreased with increasing [IO₄ ^?] but increased slightly with increasing [OH^?]. The influence of ionic strength on the reaction rate was also investigated. The oxidation resulted in oxidative deamination of pyrrolidine, giving 4-hydroxybutyrate as the product. A reaction mechanism is proposed which includes an equilibrium between [Ag(HIO₆)₂]^5? and [Ag(HIO₆)₂(OH)(H₂O)]^2?; these two Ag(III) species are reduced by pyrrolidine in parallel rate-determining steps. The rate equation derived from the proposed mechanism can explain the experimental observations. The rate constants of the rate-determining steps, together with the associated activation parameters, were calculated accordingly.     

Base dependent pyrrolidine ring pucker in aep-PNA monomers: NMR and PSEUROT analysis

The aep-PNA is a chiral and cyclic PNA analogue, which has a stronger and base dependent binding affinity with complementary DNA. To understand the base dependent properties at monomer level, the structural studies of aep-PNA-(T/C/A) monomers have been carried out focussing on the conformational analysis of pyrrolidine ring pucker in aep-PNA by ¹H NMR and the coupling constant data fitted into PSEUROT software. The results indicate that the type of pyrrolidine pucker depends on the electronic nature of substituent, implying the effect of pyrimidine or purine substituents in determining the ring pucker in monomers. This may consequently influence the aep-PNA oligomer conformation. Since pyrrolidine nucleic acids have emerged as an important class of PNA analogues, present results may have importance for their future development.     

Synthesis and spectroscopic characterization of [CoIII(salophen)(amine)2]ClO4 (amine=morpholine,pyrrolidine, and piperidine) complexes. The crystal structures of [CoIII(salophen)(morpholine)2]ClO4 and [CoIII(salophen)(pyrrolidine)2]ClO4

Three Co(III) complexes of the type [Co(salophen)(amine)₂]ClO₄, salophen=N,N′-disalicylidene-1,2-phenylendiamine dianion and amine=morpholine (1), pyrrolidine (2), and piperidine (3), have been synthesized and characterized by elemental analysis, IR, UV–Vis, ¹H, and ¹³C NMR spectroscopy. [Co(salophen)(morpholine)₂]ClO₄ (1) and [Co(salophen)(pyrrolidine)₂]ClO₄ (2) have been studied by X-ray diffraction. Compound 1 crystallizes in ribbons of complexes and perchlorates held together by weak NH⋯O and CH⋯O hydrogen bonds between morpholines and perchlorates. The latter also interconnect the chains to a 3D network. Some minor π–π interactions exist. Compound 2 crystallizes as endless chains of complexes linked by weak CH⋯O hydrogen bonds to the disordered perchlorates. The pyrrolidine moiety is turned by 90° with respect to 1 and forms intramolecular NH⋯O hydrogen bonds. The coordination polyhedra of 1 and 2 possess C_s symmetry, and the salophens are not planar in either of them.     

Structural studies of {Li} 2-lithiopyrrolidines using NMR spectroscopy

A selection of N-substituted 2-lithiopyrrolidines were prepared and their structures were investigated by ⁶Li and ¹³C NMR spectroscopy. Evidence is presented for aggregation and dynamic solvation effects, depending on the nature of the N-substituent and substituents on the pyrrolidine ring. Studies were performed with N-Boc (coordinating carbonyl group), N-methoxyethyl (coordinating methoxy group) and N-alkyl (no coordinating group) heterocycles to represent three different classes of organolithiums: dipole-stabilized, unstabilized and chelated, and unstabilized.     

Determination of chromium in sea water by atomic absorption spectrometry

A method for the determination of chromium in sea water is described which requires minimal sample preparation. The chromium from filtered samples is oxidized with permanganate, extracted with ammonium pyrrolidine dithiocarbamate into MIBK, and analyzed by atomic absorption spectrometry in a fuel-rich air-acetylene flame. Non-filterable solids are extracted with 12 M hydrochloric acid and analyzed. Detection limits for the methods are 0.05 μg 1^-1 in the soluble phase and 0.06 μg 1^-1 in the particulate phase.     

A Synthetic Method to Access Symmetric and Non-Symmetric 2-(<em>N</em>,<em>N</em><em>'</em>-disubstituted)guanidinebenzothiazoles

Symmetric and non-symmetric 2-(N-H, N-methyl, N-ethylenyl and N-aryl)guanidinebenzothiazoles were synthesized from the reaction of ammonia, methylamine, pyrrolidine and aniline with dimethyl benzo[d]thiazol-2-yl-carbono-dithioimidate (5) as intermediate. The products were characterized by ¹H-, ¹³C-NMR spectroscopy and three of them by X-ray diffraction analysis. HN-phenyl protons formed intramolecular hydrogen bonds that assist the stereochemistry of the second substituent, whereas the HN-alkyl protons were involved in intermolecular hydrogen bonding.     

Synthesis of chiral 2-(anilinophenylmethyl)pyrrolidines and 2-(anilinodiphenylmethyl)pyrrolidine and their application to enantioselective borane reduction of prochiral ketones as chiral catalysts

Chiral diamines, 2-(anilinophenylmethyl)pyrrolidines and 2-(anilinodiphenylmethyl)pyrrolidine, were prepared from N-(tert-butoxycarbonyl)pyrrolidine or (S)-proline as a starting material, respectively. These chiral diamines were efficient for the catalytic enantioselective borane reduction of acetophenone. Using (S)-2-(anilinodiphenylmethyl)pyrrolidine, chiral secondary alcohols were obtained from prochiral ketones with good to excellent enantiomeric excesses (up to 98% ee).     

A new type of organocatalyst for highly stereoselective Michael addition of ketones to nitroolefins on water

(S)-2-((Naphthalen-2-ylsulfonyl)methyl)pyrrolidine, prepared in three steps from (S)-N-Boc-2-[((4-toluenesulfonyl)oxy)methyl]pyrrolidine in 62% overall yield, was used as a new type of organocatalyst bearing a pyrrolidine and a sulfone moiety. It shows very high catalytic activity toward the direct asymmetric Michael reaction of cyclohexanone and nitroolefins. All the corresponding adducts can be furnished in 90-99% yields and with up to 98% ee and over 99:1 dr on water in the presence of this catalyst (15 mol %) without any additive.     

New organic activators for the enantioselective reduction of aromatic imines with trichlorosilane

N-Picolinoyl-(2S)-(diphenylhydroxymethyl)pyrrolidine was found to work as an organic activator in the reduction of aromatic imines to the corresponding amines by Cl₃SiH. The highest selectivity was 80% ee. These are the first data showing that N-formyl group is not always essential as N-protecting group of pyrrolidine derivatives for the reduction of imines by Cl₃SiH.     

Keto complexes from the oxidation of η6-xanthene or thioxanthene-η5-cyclopentadienyliron cation and some reactions of the fluorenone and xanthone complexes

Ligand exchange between xanthene and ferrocene gave the η⁶-xanthene-η⁵-cyclopentadienyliron cation which was oxidized in situ with KMnO₄ to give the η⁶-xanthone-η⁵-cyclopentadienyliron cation (III). Similar oxidation of the η⁶-thioxanthene-η⁶-cyclopentadienyliron cation gave a mixture of the thioxanthone complex IV and the corresponding complexed sulfone V. III and the η⁶-fluorenone-η⁵-cyclopentadienyliron cation (VI) were utilized as reactants in the synthesis of new complexes via reactions with a number of reagents. Stereospecific exo-addition to give complexed endo-alcohols were observed in the reaction of III with NaBH₄, NaBD₄ or CH₃Li, and in the reaction of VI with CH₃Li, the anion of acetonitrile, the anion of nitromethane or the phenylacetylide anion. Ring opening reactions to give complexed o,o′-disubstituted benzophenones were observed when III was treated with the anion of acetonitrile, the anion of nitromethane, methylamine, cyclohexylamine, benzylamine or pyrrolidine.     

Theoretical study on the polymerization mechanism of substituted maleimides by using a chiral catalyst with Zn

It is possible to synthesize poly(N-substituted maleimide) by using a chiral complex consisting of a zinc and N-diphenylmethyl-1-benzyl-2-pyrrolidinoethanamine (DPhBP). The optical specific rotations [α]₄₃₅²⁵ in obtained polymers depend on the chirality of ligands in the catalysts. In the present study, density functional theory (DFT) calculations were adopted to investigate the polymerization mechanism in detail. The bulky diphenylmethyl group in the chiral ligand is effective to enhance the formation of the product in the initiation reaction. The geometry related to the pyrrolidine ring of the chiral ligand in the Zn catalyst is responsible for determining the configuration of polymers. It was also confirmed that the bulky substituent on the N atom of the N-substituted maleimide is another factor for obtaining polymers with high [α]₄₃₅²⁵.     

Ruthenium(III) and iridium(III) complexes with nicotine

A new chloride-dimethylsulfoxide-ruthenium(III) complex with nicotine trans-[Ru^IIICl₄(DMSO)[H-(Nicotine)]] (1) and three related iridium(III) complexes; [H-(Nicotine)]trans-[Ir^IIICl₄(DMSO)₂] (2), trans-[Ir^IIICl₄(DMSO)[H-(Nicotine)]] (3) and mer-[Ir^IIICl₃(DMSO)(Nicotine)₂] (4) have been synthesized and characterized by spectroscopic techniques and by single crystal X-ray diffraction (1, 2, and 4). Protonated nicotine at pyrrolidine nitrogen is present in complexes 1 and 3 while two neutral nicotine ligands are observed in 4. In these three inner-sphere complexes coordination occurs through the pyridine nitrogen. Moreover, in the outer-sphere complex 2, an electrostatic interaction is observed between a cationic protonated nicotine at the pyrrolidine nitrogen and the anionic trans-[Ir^IIICl₄(DMSO)₂]^¯ complex.     

Diastereomeric P,N-bidentate amidophosphites based on (S,S)- and (R,R)-hydrobenzoin as ligands in the Pd-catalyzed asymmetric allylation

New P,N-bidentate diastereomeric amidophosphite ligands were obtained by phosphorylation of (S)-2-[(phenylamino)methyl]pyrrolidine involving (4S,5S)- and (4R,5R)-2-chloro-4,5-diphenyl-1,3,2-dioxaphospholanes. Their efficiency in the Pd-catalyzed enantioselective allylic substitution was compared, it was found that the reaction involving (E)-1,3-diphenylallyl acetate and pyrrolidine gives up to 75% ee.     

Diastereomeric P1-chiral diamidophosphites with terpene fragments in asymmetric catalysis

Diamidophosphite P¹-monodentate, ligands based on terpene alcohols and (S)- or (R)-(2-anilinomethyl)pyrrolidine, induce high enantioselectivities (ee’s up to 99%) in Pd-catalyzed allylic substitution reactions. In the Pd-catalyzed deracemization of ethyl (E)-1,3-diphenylallyl carbonate up to 92% enantioselectivity has been achieved. The Rh-catalyzed asymmetric hydrogenation of α-dehydrocarboxylic acid esters leads to a maximum of 56% ee with quantitative conversion. Diastereomeric diamidophosphites prepared from [(1S)-endo]-(−)-borneol were found to be the most efficient stereoselectors.     

Aerobic intramolecular aminothiocyanation of unactivated alkenes promoted by in situ generated iodine thiocyanate

Aerobic intramolecular aminothiocyanation of unactivated alkenes has been developed by in situ generated iodine thiocyanate under open-flask conditions. This protocol provides a concise and efficient method for synthesizing SCN-containing pyrrolidine, piperidine and indoline derivatives with isolated yields of up to 87%. Furthermore, mixing iodine and sodium thiocyanate with oxygen afforded iodine thiocyanate (ISCN) and dithiocyanatoiodate [I(SCN)₂]^- which were testified by liquid chromatography mass spectrometry. A mechanistic investigation indicates that iodonium ion and sulfonium ion intermediates might be involved in this transformation.     

Solvent-free microwave assisted synthesis of morpholine–piperidine–pyrrolidine annulated quinoline-naphthyl based chalcones and their antimicrobial activity

A new series of 2-morpholine–piperidine–pyrrolidine substituted quinoline based chalcones have been synthesized by conventional and microwave irradiation methods. All synthesized compounds were characterised by IR, ¹H and ¹³C NMR, mass spectrometry, and elemental analysis. The products were evaluated in vitro for antibacterial activity against two bacterial strains (Staphylococcus aureus, Escherichia coli) and antifungal activity against two fungal strains (Aspergillus flavus, Candida metapsilosis). 2-Piperidine substituted quinoline chalcones demonstrated high antimicrobial activity.     

Synthesis and degradation of polyurethanes containing phosphorus—Part III: Thermal degradation of a series of polyurethanes incorporating butylene phenylphosphonate structures

The principal characteristics and products of thermal degradation of a series of polyurethanes incorporating a range of concentrations of phenyl phosphonate structures were examined.The products were carbon dioxide, tetrahydrofuran, dihydrofuran, aniline, p-toluidine, N-phenyl pyrrolidine, N-(p-tolyl)pyrrolidine, cyclobutylene phenylphosphonate, butanediol, methylene bis-(4-phenyl isocyanate), 4,4′-methylene dianiline and a polyurea, while carbodiimide structures were found in the residue.The evidence has been accounted for in terms of acceptable mechanisms.     

Enantiomerically pure cyclopalladated diazaphospholidine

Enantiomerically pure (S)-2-(anilinomethyl)pyrrolidine (S)-2 was obtained from (S)-proline using a modified four-step procedure in a total yield of 56%. Diamine (S)-2 was converted to diazaphospholidine (S)-1 using ^oTolP(NMe₂)₂. The enantiomeric purity of ligand (S)-1 and diamine (S)-2 was determined by ³¹P and ¹H NMR spectroscopy, respectively, using a CN-palladacycle for their chiral derivatization. Direct cyclopalladation of (S)-1, using Pd(OAc)₂ in toluene under mild conditions regioselectively afforded the cyclopalladated complex with the (sp²)C–Pd bond. The aromatic C–H bond activation was confirmed by NMR spectral data and X-ray diffraction study of the PPh₃ derivative of the new P¹,C¹,N¹-chiral phosphapalladacycle.     

Synthesis and biological evaluation of new oxime-ether derivatives of steroid as anti-bacterial agents

Various oxime-ether derivatives of cholesterol have been synthesized by the alkylation of the steroidal oxime with 1-(2-chloroethyl) pyrrolidine hydrogen chloride/chloroethylamine hydrochloride in the presence of sodium methoxide in dry methanol. The structures of these compounds were elucidated by IR ¹H NMR, FAB mass spectroscopic methods and elemental analyses. The anti-bacterial activity was first tested in vitro by the disk diffusion method against two Gram-positive and two Gram-negative bacteria, and then the minimum inhibitory concentration (MIC) of compounds were determined. The results showed that the chloro derivatives exhibited better anti-bacterial activity than the standard drug chloramphenicol.