3,3-Bis(3,5-dimethylpyrazol-1-yl)propionic acid: A tripodal N,N,O ligand for manganese and rhenium complexes - Syntheses and structures

The tripodal N,N,O ligands 3,3-bis(3,5-dimethylpyrazol-1-yl)propionic acid (Hbdmpzp) (1) and 3,3-bis(pyrazol-1-yl)propionic acid (Hbpzp) (2) form the “missing link” between the well-known bis(pyrazol-1-yl)acetic acids and related ligands with a longer “carboxylate arm”. To illustrate the reactivity of this ligand, manganese and rhenium complexes bearing the ligand bdmpzp are reported. The complexes are compared to related compounds bearing other tripod ligands such as bis(3,5-dimethylpyrazol-1-yl)acetate (bdmpza) and 3,3-bis(1-methylimidazol-2-yl)propionate (bmip). Spectroscopic and structural data are used as a basis for comparison, as well as DFT calculations. Both ligands 1 and 2 and the complexes fac-[Mn(bdmpzp)(CO)₃] (3) and fac-[Re(bdmpzp)(CO)₃] (4) were characterised by X-ray crystallography.     

6,6′-Bis-substituted BINOL boronic acids as enantioselective and chemoselective fluorescent chemosensors for d-sorbitol

A new chiral fluorescent BINOL boronic acid 1 has been synthesized. The chiral recognition properties of 1 are drastically different from BINOL boronic acid c. Sensor 1 shows improved enantioselectivity as well as chemoselectivity toward sugar alcohols, such as d-sorbitol and d-mannitol.The enantioselectivity of sensor 1 toward d-sorbitol (K_R/K_S) is 1:35 (pH 9.0), and the chemoselectivity for d-sorbitol/d-mannitol is 20:1.     

New approaches to side-chain fluorinated bioimidazoles: 4-alkynylimidazoles as substrates for fluorination

4-Alkynylimidazoles have been prepared and their behavior as substrates for “FBr” addition (NBS+Et₃N·3HF) have been studied. Facile Markownikov addition to ethylnylimidazole 2 gave fluorobromoolefin 9a, a potential synthon for the 2-imidazolyl-2-fluoro-1-ethenyl moiety. Reaction of the lithium salt of 2 with diethyl oxalate produced imidazolylpropynoic ester 3b. However, because of the deactivating effect of the ester functionality, all attempts to carry out addition of “FBr” to 3b met with failure. Reduction of the ester gave the hydroxymethyl-substituted acetylene 4. Addition of “FBr” to this substrate and reductive removal of bromine from the product produced fluoroolefins 12, precursors to E- and Z-β-fluorourocanic acids. The same fluoroolefins can be used as intermediates in the synthesis of β-fluorohistidinols.     

Non-C2-symmetrical antimony-phosphorus ligand, (R/S)-2-diphenylphosphano-2′-di(p-tolyl)stibano-1,1′-binaphthyl (BINAPSb): preparation and its use for asymmetric reactions as a chiral auxiliary

A new non-C₂-symmetrical antimony-phosphorous ligand, (±)-2-diphenyl-phosphano-2′-di(p-tolyl)stibano-1,1′-binaphthyl (BINAPSb) 3, has been prepared from 2-bromo-2′-diphenylphosphano-1,1′-naphthyl 4 via its borane complex 6, and could be resolved by the separation of a mixture of the diastereomeric palladium complexes 8A and 8B derived from the reaction of (±)-3 with optically active palladium reagent (S)-7. The enantiomerically pure BINAPSb 3 has proved to be highly effective in the palladium-catalyzed asymmetric hydrosilylation of styrene as a chiral auxiliary.     

Synthesis and reactivity of new functionalized Pd(II) cyclometallated complexes with boronic esters

Treatment of the functionalized Schiff base ligands with boronic esters 1a, 1b, 1c and 1d with palladium (II) acetate in toluene gave the polynuclear cyclometallated complexes 2a, 2b, 2c and 2d, respectively, as air-stable solids, with the ligand as a terdentate [C,N,O] moiety after deprotonation of the -OH group. Reaction of 1j with palladium (II) acetate in toluene gave the dinuclear cyclometallated complex 5j. Reaction of the cyclometallated complexes with triphenylphosphine gave the mononuclear species 3a, 3b, 3c, 3d and 6j with cleavage of the polynuclear structure. Treatment of 2c with the diphosphine Ph₂PC₅H₄FeC₅H₄PPh₂ (dppf) in 1:2 molar ratio gave the dinuclear cyclometallated complex 4c as an air-stable solid.Deprotection of the boronic ester can be easily achieved; thus, by stirring the cyclometallated complex 3a in a mixture of acetone/water, 3e is obtained in good yield. Reaction of the tetrameric complex 2a with cis-1,2-cyclopentanediol in chloroform gave complex 2c after a transesterification reaction. Under similar conditions complexes 3a and 3d behaved similarly: with cis-1,2-cyclopentanediol, pinacol or diethanolamine complexes 3c, 3b, 3g and 3f, were obtained. The pinacol derivatives 3b and 3g experiment the Petasis reaction with glyoxylic acid and morpholine in dichloromethane to give complexes 3h, and 3i, respectively.     

Synthesis and structure of two lithium terphenyls and a “halide rich” terphenyl lithium species

The syntheses and characterization of two new terphenyl iodides 2,6-(2,3,4,5,6-Me₅C₆)₂C₆H₃I (Ar^Pmp₂I) and (Ar^Dbp₂I) are described. Treatment of these with LiBuⁿ or LiBu^t afforded their lithium salts [Ar^Pmp₂Li]₂ (2), Ar^Dbp₂{Li(OEt₂)}₂I (3), and [Ar^Dbp₂Li]₂ (4), which were spectroscopically characterized. The X-ray crystal structures of 2 and the “halide-rich” species 3 as well as that of the previously known [2,6-(2,6-Me₂C₆H₃)₂C₆H₃Li]₂ (i.e. [Ar^Xyl₂Li]₂, 1) were determined. The structures of both 1 and 2 are dimers in which the lithiums bridge the ipso carbons of the central aryl ring of each terphenyl ligand and also interact with the ipso carbons of the flanking aryl rings. The structure of 3 is a rare example of a structurally characterized “halide rich” organolithium complex and has a monomeric arrangement in which two ether-coordinated lithiums are bridged by an ipso-carbon of the central aryl ring as well as an iodine atom.     

Synthesis,structural analysis,and thermal and spectroscopic studies of methylmalonate-containing zinc(II) complexes

The synthesis, crystal structure, thermal analysis and spectroscopic studies of five zinc(II) complexes of formulae [Zn(Memal)(H₂O)]_n (1) and [Zn₂(L)(Memal)₂(H₂O)₂]_n (2-5) [H₂Memal = methylmalonic acid, and L = 4,4′-bipyridine (4,4′-bpy) (2), 1,2-bis(4-pyridyl)ethylene (bpe) (3), 1,2-bis(4-pyridyl)ethane (bpa) (4) and 4,4′-azobispyridine (azpy) (5)] are presented here. The crystal structure of 1 is a three-dimensional arrangement of zinc(II) cations interconnected by methylmalonate groups adopting the μ₃-κ²O:κO’:κO”:κO”’ coordination mode to afford a rare (10,3)-d utp-network. The structures of the compounds 2-5 are also three-dimensional and they consist of corrugated square layers of methylmalonate-bridged zinc(II) ions which are pillared by bis-monodentate 4,4′-bpy (2), bpe (3), bpa (4) and azpy (5) ligands. The Memal ligand in 2-5 adopts the μ₃-κO:κO′:κO′′:κO′′′ coordination mode. Each zinc(II) ion in 1-5 is six-coordinated with five (1)/four (2-5) methylmalonate-oxygen atoms, a water molecule (1-5) and a nitrogen atom from a L ligand (2-5) building distorted octahedral environments. The rod-like L co-ligands in 2-5 appear as useful tools to control the interlayer metal-metal separation, which covers the range 8.4311(5) Å (2) – 9.644(3) Å (5). The influence of the co-ligand on the fluorescence properties of this series of compounds has been analyzed and discussed by steady-state and time resolved spectroscopy on all five compounds in the solid state.     

Total synthesis of benzo[c]phenanthridine alkaloids based on a microwave-assisted electrocyclic reaction of the aza 6π-electron system and structural revision of broussonpapyrine

Total syntheses of the des-N-methyl (nor) type of benzo[c]phenanthridine alkaloids 1a-f and 19 and benzo[c]phenanthridine alkaloids, chelerythrine (2d), and broussonpapyrine (2f) were achieved. The key step was the construction of tetracyclic 10,11-dihydrobenzo[c]phenanthridines using a microwave-assisted electrocyclic reaction of the 2-cycloalkenylbenzaldoxime methyl ether 4 as an aza 6π-electron system, which was derived in two steps from a Suzuki-Miyaura cross-coupling reaction of 2-bromobenzaldehyde 6 with 2-(3,4-dihydro-6,7-methylenedioxynaphthyl)boronic acid pinacol ester 7. In addition, the exact structure of broussonpapyrine (2f) (2,3,9,10-tetraoxygenated type) was determined to be chelerythrine (2d).     

Palladium catalyzed Suzuki cross-coupling reactions using N,O-bidentate ligands

Palladium-catalyzed Suzuki cross-coupling reactions employing Schiff-bases as ligands toward a series of substituted arylbromides and boronic acids were pursued. In the presence of a N,O-bidentate ligand, 2-[1-(2,4,6-trimethyl-phenylimino)-ethyl]-phenol 5, the catalytic reactions could be carried out efficiently at room temperature with a wide array of arylbromides, even with electronically deactivated arenes. A deprotonated 5, 5′, chelated palladium acetate complex, [5′Pd(II)(OAc)(solv)] 8, was proposed as a precursor of a genuine catalytically active species.     

Nucleophilic substitution reactions at the Si-Cl bonds of the dichloro(methyl)silyl ligand in five- and six-coordinate complexes of ruthenium(II) and osmium(II)

Treatment of either RuHCl(CO)(PPh₃)₃ or MPhCl(CO)(PPh₃)₂ with HSiMeCl₂ produces the five-coordinate dichloro(methyl)silyl complexes, M(SiMeCl₂)Cl(CO)(PPh₃)₂ (1a, M = Ru; 1b, M = Os). 1a and 1b react readily with hydroxide ions and with ethanol to give M(SiMe[OH]₂)Cl(CO)(PPh₃)₂ (2a, M = Ru; 2b, M = Os) and M(SiMe[OEt]₂)Cl(CO)(PPh₃)₂ (3a, M = Ru; 3b, M = Os), respectively. 3b adds CO to form the six-coordinate complex, Os(SiMe[OEt]₂)Cl(CO)₂(PPh₃)₂ (4b) and crystal structure determinations of 3b and 4b reveal very different Os-Si distances in the five-coordinate complex (2.3196(11) Å) and in the six-coordinate complex (2.4901(8) Å). Reaction between 1a and 1b and 8-aminoquinoline results in displacement of a triphenylphosphine ligand and formation of the six-coordinate chelate complexes M(SiMeCl₂)Cl(CO)(PPh₃)(κ²(N,N)-NC₉H₆NH₂-8) (5a, M = Ru; 5b, M = Os), respectively. Crystal structure determination of 5a reveals that the amino function of the chelating 8-aminoquinoline ligand is located adjacent to the reactive Si-Cl bonds of the dichloro(methyl)silyl ligand but no reaction between these functions is observed. However, 5a and 5b react readily with ethanol to give ultimately M(SiMe[OEt]₂)Cl(CO)(PPh₃)(κ²(N,N-NC₉H₆NH₂-8) (6a, M = Ru; 6b, M = Os). In the case of ruthenium only, the intermediate ethanolysis product Ru(SiMeCl[OEt])Cl(CO)(PPh₃)(κ²(N,N-NC₉H₆NH₂-8) (6c) was also isolated. The crystal structure of 6c was determined. Reaction between 1b and excess 2-aminopyridine results in condensation between the Si-Cl bonds and the N-H bonds with formation of a novel tridentate “NSiN” ligand in the complex Os(κ³(Si,N,N)-SiMe[NH(2-C₅H₄N)]₂)Cl(CO)(PPh₃) (7b). Crystal structure determination of 7b shows that the “NSiN” ligand coordinates to osmium with a “facial” arrangement and with chloride trans to the silyl ligand.     

Synthesis, crystal structures and properties of three new mixed-ligand d metal complexes constructed from pyridinecarboxylate and in situ generated amino-tetrazole ligand

Three new metal-organic frameworks, [Zn(atz)(nic)]_n(1), [Zn(atz)(isonic)]_n·nHisonic(2) and [Cd(atz)(isonic)]_n(3) (Hnic=nicotinic acid, Hisonic=isonicotinic acid), have been firstly synthesized by employing mixed-ligand of pyridinecarboxylate with the in situ generated ligand of 5-amino-tetrazolate(atz⁻), and characterized by elemental analysis, IR spectroscopy, TGA and single crystal X-ray diffraction. The results revealed that 1 presents a two-dimensional (2D) “sql” topological network constructed from the linear chain subunit of Zn(nic)₂ and atz⁻ ligand. A remarkable feature of 2 is a 2-fold interpenetrated diamondoid network with free Hisonic molecules locating in the channels formed by the zigzag chain subunits of Zn(isonic)₂. Complex 3 is a 3D non-interpenetrated pillared framework constructed from the double chain subunits of Cd-COO⁻-Cd. It possesses a rarely observed (4,6)-connected “fsc” topology. The thermal stabilities and fluorescent properties of the complexes were investigated. All of these complexes exhibited intense fluorescent emissions in the solid state at room temperature.     

Synthesis of novel halopyridinylboronic acids and esters. Part 4: Halopyridin-2-yl-boronic acids and esters are stable, crystalline partners for classical Suzuki cross-coupling

This paper describes some methods for the synthesis and the isolation of novel 5 or 6-halopyridin-2-yl-boronic acids and esters 3, 4, 7. These compounds are prepared via a regioselective halogen-metal exchange using n-butyllithium and subsequent quenching with triisopropylborate starting from appropriate dihalopyridines. All substrates studied to date provided a single regioisomeric boronic acid or ester product. Additionally, these compounds have been found to undergo Pd-catalysed coupling with arylhalides and authorise a strategy to produce new pyridines libraries.     

Endo and exo cyclometallated iron carbonyl complexes derived from N-(N′-methyl-2-pyrrolylmethylidene)-2-thienylmethylamine

The reaction of N-(N′-methyl-2-pyrrolylmethylidene)-2-thienylmethylamine (1) with Fe₂(CO)₉ in refluxing toluene gives endo cyclometallated iron carbonyl complexes 2 and 5, exo cyclometallated iron carbonyl complex 3, and unexpected iron carbonyl complex 4. Complexes 2, 3, and 5 are geometric isomers. Complex 5 differs from complex 2 in the switch of the original substituent from α to β position of the pyrrolyl ring, and the pyrrolyl ring bridges to the diiron centers in μ-(3,2-η¹:η²) coordination mode in stead of μ-(2,3-η¹:η²). In complex 4, the pyrrolyl moiety of the original ligand 1 has been displaced by a thienyl group, which comes from the same ligand. Single crystals of 2, 3, and 5 were subjected to the X-ray diffraction analysis. The major product 2 undergoes: (i) thermolysis to recover the original ligand 1; (ii) reduction to form a hydrogenation product, 6, of the original ligand; (iii) substitution to form a monophosphine-substituted complex 7; (iv) chemical as well as electrochemical oxidation to produce a carbonylation product, γ-butyrolactam 8.     

Synthetic studies of neoclerodane diterpenoids from Salvia splendens and evaluation of opioid receptor affinity

Salvinorin A (1), a neoclerodane diterpene from the hallucinogenic mint Salvia divinorum, is the only known non-nitrogenous and specific κ-opioid agonist. Several structural congeners of 1 isolated from Salvia splendens (2-8) together with a series of semisynthetic derivatives (9-24), some of which possess a pyrazoline structural moiety (9, 19-22), have been tested for affinity at human μ, δ, and κ opioid receptors. None of these compounds showed high affinity binding to these receptors. However, 10 showed modest affinity for κ receptors suggesting that other natural neoclerodanes from different Salvia species may possess opioid affinity.     

Palladium complexes of amido-functionalized N-heterocyclic carbenes as effective precatalysts for the Suzuki-Miyaura C-C cross-coupling reactions of aryl bromides and iodides

A series of air-stable, robust and highly active palladium based precatalysts of amido-functionalized N-heterocyclic carbenes for the Suzuki-Miyaura C-C cross-coupling reaction has been designed. In particular, the [1-R-3-{N-(benzylacetamido)imidazol-2-ylidene]₂PdCl₂ [R = i-Pr (1c) and CH₂Ph (2c)] complexes efficiently carried out the Suzuki-Miyaura coupling of the aryl bromide and iodide substrates with phenyl boronic acid in good to excellent yields in air at 90 °C in 12 h. Quite interestingly, of these palladium precatalysts, the i-propyl derivative (1c) exhibited superior activity as compared to the benzyl derivative (2c). The density functional theory (DFT) studies carried out on the 1c and 2c complexes revealed the strong σ-donating nature of the NHC ligand as reflected in their high d/b ratio [i.e. forward σ-donation (d) to backward π-donation (b)] of these complexes and, thus, point towards greater stability of the Pd-NHC interaction in these complexes.     

Synthesis of novel fluorescent 3-aryl- and 3-methyl-7-aryl-[1,2,3]triazolo[1,5-a]pyridines by Suzuki cross-coupling reactions

Two series of compounds, 3-aryl- (series A, compounds 2a-j) and 3-methyl-7-aryl-[1,2,3]triazolo[1,5-a]pyridines (series B, compounds 3a-j) have been synthesized by Suzuki cross-coupling reactions, with a triazolopyridine halide and an aryl or heteroaryl boronic acid in moderate to good yields. All compounds obtained are fluorescents, the quantum yields, particularly those of compounds 3f-j, are very high.     

Preparation of α,α-difluoroalkanesulfonic acids

Chlorodifluoromethanesulfonic acid (1) was prepared using a new procedure starting from perchloromercaptan, which is readily obtained from chlorination of CS₂. Modified Swarts reaction transformed N,N-diethyl trichloromethanesulfenamide into N,N-diethyl chlorodifluoromethanesulfenamide, and the latter species was further oxidized and hydrolyzed into chlorodifluoromethanesulfonic acid. The preparations of other two new α,α-difluoroalkanesulfonic acids, phenyl difluoromethanesulfonic acid (2) and 2-phenyl-1,1,2,2,-tetrafluoroethanesulfonic acid (3), are also disclosed. The acids 2 and 3 are stable in the forms of sodium (lithium) salts or in aqueous solutions; however, the pure forms of 2 and 3 can readily undergo defluorinations. 1-3 and their salts have potential applications as superacid catalysts and lithium battery electrolytes.     

Synthesis and pharmacological evaluation of 6a,7-dihydro-6H,13H-pyrazino[1,2-a;4,5-a′]diindole analogs as melatonin receptor ligands

The synthesis of two melatonin-derived analogs of the novel 6a,7-dihydro-6H,13H-pyrazino[1,2-a;4,5-a′]diindole ring system is described. The non-methoxy and methoxy analogs, 4a and 4b were prepared in seven steps starting from indoline-2-carboxylic acid 5a and 5-methoxyindoline-2-carboxylic acid 5b, respectively. While 4a exhibited micromolar affinities for both melatonin receptors, the methoxy analog 4b displayed moderate affinity for MT₂ receptors (K_i=0.41 μM) being 4.4-fold higher than for the MT₁ subtype.     

EPR studies on regio-selective H-abstraction by “magic blue” reagent from polymers

The radical reactions of polyolefin and olefin copolymers (4-9), polydienes and diene coplymers (10-15), and polysiloxane (16) with “magic blue” reagent containing H-abstracting agent-bis{perfluoro-1-[1-(2-fluorosulfonyl)ethoxy]ethyl}nitroxide [FSO₂CF₂CF₂OCF(CF₃)]₂N(O) (2)and spin trap-perfluoro-1-nitroso-[1-(2-fluoro-sulfonyl)ethoxy]ethane FSO₂CF₂CF₂OCF(CF₃)NO (3) were studied by EPR detection of the spin adducts of the corresponding polymeric radicals generated in the H-abstraction step to the spin trap 3, namely, the nitroxides FSO₂CF₂CF₂OCF(CF₃)N(O) (polymer-H) 17-29. EPR studies have provided information about the regio-selectivity of H-abstraction, the subsequent radical steps followed H-abstraction and grounded a possibility of employing “magic blue” reagent in polymer modification via H-abstraction-initiated grafting polymerization.     

EPR studies on H-abstraction from methylbenzenes by “magic blue” reagent

After mixing a methylbenzene 4 with “magic blue” solution in F113 (CClF₂CCl₂F) containing bis{perfluoro[1-(2-fluorosulfonyl)ethoxy]ethyl}nitroxide 2 and perfluoro-1-nitroso-1-[1-(2-fluorosulfonyl)ethoxy]ethane 3 at room temperature, benzylic H-atom of 4 could be selectively abstracted by 2, and benzyl radical 5 thus generated was immediately trapped by 3. Based on hyper-fine splitting constants (hfsc), the structure of the spin adducts perfluoro[1-(2-fluorosulfonyl)ethoxy]ethyl benzyl nitroxides 6 derived from seven methylbenzenes have been identified. The mechanism of the H-abstraction/spin trapping process is also discussed.