Michael addition of malononitrile to indenones: Synthesis and characterization of 2-(1-oxo-2,3-dihydro-1H-inden-2-yl) (aryl)(methyl)malononitrile derivatives

Indanones 3 were prepared from the reaction of indanone (1) with corresponding benzaldehyde derivatives 2, as described in the literature. Then, indenones 3 were subjected to KOtBu-catalyzed Michael addition with malononitrile to give a mixture of diastereomers 5 with a low conversion and no diastereoselection. Utilization of phase-transfer catalyst such as benzyltriethylammonium chloride or N-benzylcinchonidinium chloride had a positive effect on both conversion and diastereoselection. The structure of diastereomers 5 was determined by spectroscopic methods (NMR, IR).     

Diastereoselective formation of cyclochiral amino acids-substituted resorcin[4]arenes

The Mannich reaction between selectively tetratosylated resorcin[4]arene, formaldehyde and (S)-phenylalanine (or (S)-phenylglycine) methylamide gave cyclochiral mono- or dibenzoxazines with high diastereoselection as revealed by NMR and X-ray structural studies. X-ray structures of the products show the variety of intramolecular interactions that can be responsible for the diastereoselection of this acid-catalyzed reaction.     

Diastereoselection in the formation of contiguous quaternary carbon stereocenters by the intramolecular Heck reaction

The second in a series of two papers, this study examines the origins of diastereoselection in the second ring closure of the highly diastereoselective double Heck cyclization of cyclohexenes 1 and 3 that form contiguous quaternary stereocenters. Seven model substrates were synthesized and cyclized to examine the structural features responsible for imparting diastereoselection in the second intramolecular Heck reaction. These studies demonstrate that stereoselection in the formation of the second spirooxindole ring results from the avoidance of steric interactions in the insertion step with the spirooxindole formed in the first Heck cyclization. An axial substituent (carbonyl or arene) is required at the allylic position for high levels of diastereoselection to be realized.     

Synthesis,characterization, and structures of nickel(II) and palladium(II) complexes of aromatic thiohydrazides

Nickel(II) and palladium(II) form neutral 1?:?2 chelates with aromatic thiohydrazides, for example. thiobenzhydrazide, o-hydroxythiobenzhydrazide, furan-2-thiohydrazide, and thiophen-2-thiohydrazide. All the compounds are diamagnetic and have been characterized by elemental analysis and spectroscopic methods. o-Hydroxythiobenzhydrazido complexes of nickel(II) and palladium(II) were crystallized from DMSO and their structures were solved by X-ray diffraction. The complexes are isostructural with planar structures. Metal ion is linked to two identical deprotonated ligands through trans hydrazinic nitrogen and sulfur. Hydrogen of OH is involved in intramolecular hydrogen-bonding.     

Template‐Assembled Synthetic G‐Quadruplex (TASQ): A Useful System for Investigating the Interactions of Ligands with Constrained Quadruplex Topologies

A new biomolecular device for investigating the interactions of ligands with constrained DNA quadruplex topologies, using surface plasmon resonance (SPR), is reported. Biomolecular systems containing an intermolecular‐like G‐quadruplex motif 1 (parallel G‐quadruplex conformation), an intramolecular G‐quadruplex 2 , and a duplex DNA 3 have been designed and developed. The method is based on the concept of template‐assembled synthetic G‐quadruplex (TASQ), whereby quadruplex DNA structures are assembled on a template that allows precise control of the parallel G‐quadruplex conformation. Various known G‐quadruplex ligands have been used to investigate the affinities of ligands for intermolecular 1 and intramolecular 2 DNA quadruplexes. As anticipated, ligands displaying a π‐stacking binding mode showed a higher binding affinity for intermolecular‐like G‐quadruplexes 1 , whereas ligands with other binding modes (groove and/or loop binding) showed no significant difference in their binding affinities for the two quadruplexes 1 or 2 . In addition, the present method has also provided information about the selectivity of ligands for G‐quadruplex DNA over the duplex DNA. A numerical parameter, termed the G‐quadruplex binding mode index (G4‐BMI), has been introduced to express the difference in the affinities of ligands for intermolecular G‐quadruplex 1 against intramolecular G‐quadruplex 2 . The G‐quadruplex binding mode index (G4‐BMI) of a ligand is defined as follows: G4‐BMI=K_D^intra/K_D^inter, where K_D^intra is the dissociation constant for intramolecular G‐quadruplex 2 and K_D^inter is the dissociation constant for intermolecular G‐quadruplex 1 . In summary, the present work has demonstrated that the use of parallel‐constrained quadruplex topology provides more precise information about the binding modes of ligands.     

Cobalt(0)-mediated addition of α-haloesters and α-haloketones to (R)-2,3-O-cyclohexylideneglyceraldehyde

Low-valent cobalt complexes were used in Reformatsky-type additions of α-haloesters and in aldol-type reactions of α-haloketones to (R)-2,3-O-cyclohexylideneglyceraldehyde. Addition products were obtained in good yield with reasonable to high diastereoselection. The addition of methyl 4-bromocrotonate, which took place exclusively at the γ-carbon, was regioselective.     

Bis(1,4-di-tert-butyl-1,4-diazabutadiene)copper(i) [(3,6-di-tert-butyl-o-benzosemiquinono)(3,6-di-tert-butyl-catecholato)cuprate(ii)]. The molecular structure and intramolecular electron transfer

Bis(1,4-di-tert-butyl-1,4-diazabutadiene)copper(i) [(3,6-di-tert-butyl-o-benzosemiquinono)(3,6-di-tert-butylcatecholato)cuprate(ii)] (1) was synthesized. Complex 1 contains the 1,4-di-tert-butyl-1,4-diazabutadiene and 3,6-di-tert-butyl-o-benzoquinone ligands in the reduced form. The structure of 1 was established by X-ray diffraction analysis. The ESR spectra indicate that dissolution of complex 1 in organic solvents (toluene, THF, CH₂Cl₂, etc.) leads to its symmetrization to give neutral complex 2, which occurs in solutions as an equilibrium mixture of two redox isomers, viz., catecholate (Cat) complex 2c and semiquinone (SQ) complex 2s. In the coordination sphere of the copper atom, the reversible intramolecular metal—ligand electron transfer can proceed as successive steps as exemplified by the reactions of 2 with CO and 2,6-dimethylphenylisonitrile. Copper(i) o-semiquinone complex 2s can be reversibly transformed into copper(ii) catecholate complex 2c through electron transfer from the copper(i) atom to the SQ ligand. The subsequent addition of the neutral ligand (CO or CNAr) to 2c induces, in turn, electron transfer from the Cat ligand to the copper(ii) atom accompanied by the transformation of the catecholate complex into the o-semiquinone complex. In the case of CO, this transformation is also reversible and is efficiently controlled by the temperature.     

Photoinitiated processes in 1-p-tolylsulfonylazo-2,4,6,8-tetrakis(tert-butyl)phenoxazine

New photochromic compound 1-p-tolylsulfonylazo-2,4,6,8-tetrakis(tert-butyl)phenoxazine containing the intramolecular hydrogen bond NH...N and the corresponding model structures 2,4,6,8-tetrakis(tert-butyl)-1-(veratroylazo)phenoxazine and 2,4,6,8-tetrakis(tert-butyl)-N-acetyl-1-(p-tolylsulfonylazo)phenoxazine were synthesized and studied. The data obtained suggested the mechanism of the photoreaction resulting in the accumulation of betaine 1-hydroxy-2,4,6,8-tetrakis(tert-butyl)-10-tolylsulfonylphenoxazin-9-one. The photochromic transformations in the molecule under study are due to intramolecular proton phototransfer followed by E–Z-isomerization about the N–N bond and the formation of betaine 1-hydroxy-2,4,6,8-tetrakis(tert-butyl)-10-tolylsulfonylphenoxazin-9-one. The molecular and crystal structure of the photoproduct was studied by X-ray analysis.     

Equilibrium studies of Mn(II), Mg(II), Ca(II), Sr(II) and Ba(II) withp-fluoro-,p-chloro-,p-bromo-,p-methyl-benzoylacetones and 1-(4-fluorophenyl)-1,3-pentanedione

The rawpH-data, obtained from the potentiometric titrations of the titled ligands with NaOH in 75% (v/v) dioxane-water mixture performed at 20, 30 and 40°C at constant ionic strength (=0.1M-NaClO₄), have been adequately corrected for dilution, and solvent effects in order to evaluate thermodynamic dissociation constants. Variance of the latter as a function of temperature has also been accounted for. The differing magnitudes of thermodynamic dissociation constants of the titled ligands have been explained on the basis of the non coplanar orientation of the phenyl ring in the ligands and a comparison has been made with those of unsubstituted benzoylacetone, dibenzoylmethane and acetylacetone.Following similar technique, thermodynamic stepwise and overall formation constants of the titled metal-ligand systems have been obtained and the results correlated with ligand basicity inverse metal crystal radii and second potentials of metals. Decrease in the free enthalpy (–G) of complexation reaction has also been evaluated.

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Untersuchung der Gleichgewichte von Mn(II), Mg(II), Ca(II), Sr(II) und Ba(II) mit p-Fluor-, p.-Chlor-, p-Brom-, p-Methyl-benzoylaceton und 1-(4-Fluorphenyl)-1,3-pentanedion

Zusammenfassung Aus der potenitometrischen Titration der Titelverbindungen mit NaOH in 75 (v/v) Dioxan—Wasser bei, 20, 30 und 40°C bei konstanter Ionenstärke (=0,1M-NaClO₄) wurden die thermodynamischen Dissoziationskonstanten ermittelt. Verdünnungs-, Lösungsmittel-und Temperatureffekte wurden berücksichtigt. Die unterschiedlichen Dissoziationskonstanten werden mit der Nichtplanarität des Phenylrings in den Liganden erklärt. Außerdem wurden die Komplexbildungskonstanten bestimmt; sie sind in die Diskussion miteinbezogen.

     

Synthesis and stereochemical nonrigidity of isomeric Zn(ii)bis-[N-isopropyloxy(mercapto)naphthaldiminates]

Kinetics and reaction mechanisms governing inversion of the tetrahedral configuration at the metal center in the series ofbis-chelate Zn(II) complexes of 3,2-, 1,2-, and 2,1-oxy(mercapto)naphthaldimines, respectively4–6, have been studied with the use of dynamic¹H NMR spectroscopy. A polytopal rearrangement of the diagonal twist type has been found to be an energetically preferable pathway of the inversion reaction for complexes4 and5 with a ZnN₂O₂ coordination site, whereas the inversion reaction for complexes with a ZnN₂S₂ coordination site occurs by an intramolecular dissociation-recombination pathway that involves cleavage of a Zn-N coordination bond. In the case of complexes6, the inversion reaction is governed mainly by intramolecular degenerate ligand exchange reactions.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11. pp. 2261–2265, November, 1995.This work was supported by the Russian Foundation for Basic Research (project No. 93-03-18692) and the International Science Foundation (grant No. RNJ 000).     

Catalytic enantioselective conjugate addition of dialkyl zinc reagents to α,β-unsaturated ketones mediated by new phosphite ligands containing binaphthalene/1,2-diphenylethane moieties: a practical synthesis of (R)-(−)-muscone

New diastereoisomeric phosphites based on either (R)- or (S)-2,2′-dihydroxy-1,1′-binaphthyl (BINOL) and having the chiral alcoholic moiety derived from the monobenzyl ether of (R,R)-1,2-diphenylethane-1,2-diol have been prepared and used as chiral ligands in the enantioselective copper-catalyzed 1,4-addition of diethylzinc to chalcone and 2-cyclohexen-1-one (enantiomeric excesses up to 48%). With the (aR,R,R) ligand dimethylzinc adds enantioselectively to (E)-cyclopentadecen-2-en-1-one to give (R)-(−)-muscone (68% yield, 78% ee). This provides an efficient access to a valuable ingredient of the perfume industry. However, with the (aS,R,R) ligand, (S)-(+)-muscone is obtained with longer reaction times (37% yield and 10% ee) with a very high double diastereoselection effect being observed.     

Total synthesis and absolute stereochemical assignment of (+)- and (-)-galbulimima alkaloid 13

We describe the total synthesis of (+)- and (-)-galbulimima alkaloid 13. The absolute stereochemistry of natural (-)-galbulimima alkaloid 13 is revised to 2S. Sequential use of catalytic cross-coupling and cross-metathesis reactions followed by an intramolecular Diels-Alder reaction provided the required trans-decalin AB-ring system and masked the C16 carbonyl as an N-vinyl carbamate for late-stage unveiling in the form of the necessary C16 enone. A vinyl radical cyclization secured the C-ring, while successful execution of our strategy for introduction of the CDE-ring system in complex galbulimima alkaloids provided the target pentacycle with complete diastereoselection.     

Molecular and chemical dynamics of a biradical with six-coordinate silicon atom

The intramolecular dynamics of a silicon biradical complex witho-semiquinone ligands was studied in a frozen toluene solution. Analysis of the broadening and shifts of the canonical components in the ESR spectrum of this biradical allows one to detect the abrupt reorientation of the magnetic axes due to intramolecular single bond-unpaired electron exchange. The frequencies of chemical exchange at low temperatures were estimated. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1726–1730, October, 1993.     

Intramolecular hydrogen bonding in dichloridobis(3,5‐di‐tert‐butyl‐1H‐pyrazole‐κN2)cobalt(II) as a consequence of ligand steric bulk

The title compound, [CoCl₂(C₁₁H₂₀ClN₂)₂], forms two intramolecular hydrogen bonds [graph set S(5)] between the N atoms of the pyrazole ligands and the chloride ligands. This hydrogen‐bonding motif is uncommon among related compounds but occurs here because of the bulk of tert‐butyl substituents on the pyrazole ligands which shield the central metal atom to a significantly larger extent than pyrazole ligands with smaller 3,5‐substituents.     

Catalytic asymmetric assembly of stereodefined propionate units: an enantioselective total synthesis of (-)-pironetin

Double diastereoselection in alkaloid-catalyzed acyl halide-aldehyde cyclocondensation (AAC) reactions provides a strategy for realizing syn- or anti-selective propionate aldol additions from a common reaction manifold. Matched AAC homologation of enantioenriched aldehydes afford cis-disubstituted beta-lactones as surrogates for syn aldols; the mismatched AAC reactions provide anti-selective aldols in the form of trans-disubstituted 2-oxetanones. The utility of this reaction technology in synthesis activities is exemplified in a catalytic asymmetric total synthesis of (-)-pironetin.     

"Matched/mismatched" diastereomeric dirhodium(II) carboxamidate catalyst pairs. Structure-selectivity correlations in diazo decomposition and hetero-Diels-Alder reactions

Homo-ligated dirhodium(II) carboxamidates provide well-defined structural frameworks with which to investigate catalyst-controlled multiple asymmetric induction ("match/mismatch" effects). Diastereomeric pairs of methyl 2-oxoimidazolidine-4(S)-carboxylate ligands containing 2-phenylcyclopropane (4S,2'S,3'S-HMCPIM and 4S,2'R,3'R-HMCPIM) and N-benzenesulfonylproline (4S,2'S-HBSPIM and 4S,2'R-HBSPIM) attachments at the 1-N-acyl site have been prepared; the resulting (cis-2,2)-Rh(2)L(4) compounds have been produced in good yields, and the X-ray crystal structure of each dirhodium(II) compound has been obtained. The incorporation of additional stereocenters into the dirhodium(II) ligands leads to recognizable levels of double asymmetric induction for C-H insertion, cyclopropanation, and hetero-Diels-Alder cycloaddition applications. The configurationally "matched" cases provide modest increases in enantioselectivity for intramolecular C-H insertion reactions relative to the model catalyst Rh(2)(MPPIM)(4), but applications of the configurationally mismatched catalysts result in significant lowering of enantioselectivity. The Rh(2)(BSPIM)(4) catalysts show the highest degree of differential selectivity. Hetero-Diels-Alder reactions show inverse behavior from the configurationally matched and mismatched Rh(2)L(4) catalysts to that found in the metal carbene transformations.     

Quantum chemical study of the transformation of 2-(N-alkylamino)-3-(indol-1-yl)-and 2-(N-alkylamino)-3-(indol-3-yl)maleimides by protic acids: Tandem hydride transfer/cyclization mechanism

The geometric parameters, the charge distribution, and the energetics of N-methyl-2-(N-ethylanilino)-3-(indol-1-yl)-and N-methyl-2-(N-ethylanilino)-3-(indol-3-yl)maleimides and their conjugated acids were studied by density functional theory calculations at the B3LYP/6-31G(d) level. The mechanism of the tandem hydride transfer/cyclization sequence, which occurs after protonation of N-methyl-2-(N-ethylanilino)-3-(indol-1-yl)-and N-methyl-2-(N-ethylanilino)-3-(indol-3-yl)maleimides, was analyzed. The investigation of the potential energy surface for the tandem hydride transfer/cyclization of the iminium cation that formed upon protonation revealed that the hydride transfer followed by intramolecular cyclization at position 7 of the indole fragment in N-methyl-2-(N-ethylanilino)-3-(indol-1-yl)maleimide is the preferable process, unlike alternative intramolecular cyclization involving the cationic center at the C(2) atom of the indole fragment and the benzene ring of the N-ethylaniline fragment of the indoleninium cation in N-methyl-2-(N-ethylanilino)-3-(indol-3-yl)maleimide. A study of the key intermediates of the assumed reaction mechanism demonstrated that these intermediates are actually stationary points on the potential energy surface (minima and transition states). Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2069–2073, December, 2006.     

Theoretical investigation of the decomposition mechanisms of N-(2-chloroethyl)-N-nitrosourea

The initial reaction mechanisms of N-(2- chloroethyl)-N-nitrosourea (CENU) decomposition have been investigated at the MP2/6-311+G(d,p) level. The mechanistic processes considered were the hydrogen shifting from the nitrogen to the oxygen of the nitroso group, the oxygen of the nitroso and the carbonyl groups nucleophilic displacing the chlorine. The computational results showed that the energy barrier of retro-ene reaction was lower in the gas phase than that of substitution reactions. In the solvent, however, the energy values of each barrier in these three processes approach each other. It is concluded that the CENU decomposition in solvent can proceed via retro-ene reaction and intramolecular substitution reactions.     

A Reusable MOF‐Supported Single‐Site Zinc(II) Catalyst for Efficient Intramolecular Hydroamination of o‐Alkynylanilines

The exploitation of new and active earth‐abundant metal catalysts is critical for sustainable chemical production. Herein, we demonstrate the design of highly efficient, robust, and reusable Zn^II‐bipyridine‐based metal–organic framework (MOF) catalysts for the intramolecular hydroamination of o‐alkynylanilines to indoles. Under similar conditions homogeneous catalytic systems mainly provide hydrolysate. Our results prove that MOFs support unique internal environments that can affect the direction of chemical reactions. The Zn^II‐catalyzed hydroamination reaction can be conducted without additional ligands, base, or acid, and is thus a very clean reaction system with regard to its environmental impact.     

Dichlorobis(cycloalkylamine)platinum(II) complexes structure activity relationship on the human MDA-MB-231 breast cancer cell line

Summary The syntheses of dichlorobis(cycloalkylamine)platinum(II) complexes withcis andtrans cycloalkylamine ligands [cis-PtCl₂(C₃H₅NH₂)₂ tocis-PtCl₂(C₈H₁₅NH₂)₂ (3–8) andtrans-PtCl₂(C₇H₁₃NH₂)₂ (9) andtrans-PtCl₂(C₈H₁₅NH₂)₂ (10)] are described. The distinction betweencis andtrans isomers was achieved by¹H-NMR spectroscopy. The antitumor activity was determined on the cell proliferation of the human MDA-MB-231 breast cancer cell line during long-term drug exposure. The complexes with small cycloalkylamine ligands (3–6) were inferior, those with large cycloalkylamine ligands were comparable (7) or superior (8) to cisplatin. Surprisingly, thecis/trans isomers7/9 and8/10 were equally active. All cycloalkylamine ligands were inactive. IR-spectroscopic studies showed that the size of the cycloalkylamine ring does not lead to significant differences in the Pt-Cl binding strength. Therefore it is assumed that the markedly stronger antitumor activity of the higher homologues,7–10, is not the result of a faster reaction with bionucleophils such as DNA. A possible explanation of the high activity of7–10 is the strong lipophilicity of the complexes. This assumption was confirmed by toxicity tests against confluent cultures.In memory of Professor Dr. Günter Gliemann, late director of the Institut für Physikalische und Theoretische Chemie, Universität Regensburg.