Iron-Catalysed Remote C(sp3)−H Azidation of O-Acyl Oximes and N-Acyloxy Imidates Enabled by 1,5-Hydrogen Atom Transfer of Iminyl and Imidate Radicals: Synthesis of γ-Azido Ketones and β-Azido Alcohols

In the presence of a catalytic amount of iron(III) acetylacetonate [Fe(acac)₃], the reaction of structurally diverse ketoxime esters with trimethylsilyl azide (TMSN₃) afforded γ-azido ketones in good to excellent yields. This unprecedented distal γ-C(sp³)−H bond azidation reaction went through a sequence of reductive generation of an iminyl radical, 1,5-hydrogen atom transfer (1,5-HAT) and iron-mediated redox azido transfer to the translocated carbon radical. TMSN₃ served not only as a nitrogen source to functionalise the unactivated C(sp³)−H bond, but also as a reductant to generate the catalytically active Fe^II species in situ. Based on the same principle, a novel β-C(sp³)−H functionalisation of alcohols via N-acyloxy imidates was subsequently realised, leading, after hydrolysis of the resulting ester, to β-azido alcohols, which are important building blocks in organic and medicinal chemistry.     

An expedient route for the reduction of carboxylic acids to alcohols employing 1-propanephosphonic acid cyclic anhydride as acid activator

A simple and efficient method for the synthesis of alcohols from the corresponding carboxylic acids is described. Activation of carboxylic acid with 1-propanephosphonic acid cyclic anhydride (T3P) and subsequent reduction using NaBH₄ yield the alcohol in excellent yields with good purity. Reduction of several alkyl/aryl carboxylic acids and N^α-protected amino acids/peptide acids as well as N^β-protected amino acids was successfully carried out to obtain corresponding alcohols in good yields. All the products were fully characterized by ¹H NMR and mass spectral analyses. The procedure is mild, simple and the isolation of the products is easy.     

Synthesis,crystal structures and spectral properties of cobalt (Ⅱ) complexes:[ CoL (N_3) ] ·ClO_4 and CoL (N_3)_2 [L=tris ((3,5-dimethylpyrazol-1-yl) methyl) amine

Two monomeric cobalt(Ⅱ)complexes,[CoL(N3)] ClO4(1)and CoL(N3)2(2),where L is tris((3,5-dimethylpyrazol-1-yl)methyl)amine,were synthesized and their crystal structures were determined by X-ray diffraction technique.Complex 1 is five coordinated with one azide nitrogen atom and four nitrogen atoms of the tris((3,5-dimethylpyrazol-l-yl)-methyl)amine ligand,and the metal center is in distorted trigonal bipyramidal environment.Complex 2 is six coordinated distorted octahedron with the two azide nitrogen atoms and four nitrogen donors of the tris((3,5-dimethylpyrazol-1-yl)-methyl)amine ligand.The solution behaviors of the title complexes have been further investigated by UV-Vis,and 1H NMR analysis.It is found that the formation of 1 and 2 depends on the molar ratio of the azide ion to metal salt and ligand Complex 1 attached with one azide group is more stable and easy to generate than complex 2 incorporated with two azide groups,and the reasons were well discussed.     

Lewis Acid Promoted Single C–F Bond Activation of the CF3 Group: SN1′-Type 3,3-Difluoroallylation of Arenes with 2-Trifluoromethyl-1-alkenes

Activation of the sp³ C−F bond in 2-trifluoromethyl-1-alkenes was accomplished through treatment with a Lewis acid. In the presence of an equimolar amount of EtAlCl₂, the (trifluoromethyl)alkenes readily underwent an S_N1′-type reaction with arenes through a Friedel–Crafts-type mechanism via elimination of a fluoride ion to afford 3,3-difluoroallylated arenes in good yields. This selective activation of one C−F bond of the CF₃ group provides a synthetic method for accessing biologically and synthetically important 1,1-difluoro-1-alkenes.     

Dirhodium(II)-Catalyzed C(sp2)−H Azidation of Benzaldehydes

Multiple steps are needed to achieve the C−H functional of aromatic aldehyde, since the C−H functional reaction usually occurs preferentially at the aldehydic C−H bond over the aryl C−H bond. We report an efficient azidation method mediated by dirhodium(II) catalysts to achieve the direct aryl azidation of aromatic aldehydes avoiding the simultaneous use of protected aldehydes and prefunctionalized arenes. The regioselectivity of this method is similar to those of typical aromatic electrophilic substitution reactions. The resulting azidobenzaldehyde products are versatile building blocks or precursors for the synthesis of many biologically active compounds. The mechanism studies indicate that the one-electron oxidative intermediate Rh₂^(II,III)N₃ is responsible for the azide transfer.     

Reactions of arylacetylenic compounds with arenes in the presence of aluminum halides

Conjugated arylacetylenic ketones and aldehydes, propargyl-type alcohols, and arylacetylenes reacted with arenes in the presence of AlBr₃ or AlCl₃ as catalyst to give substituted indenes. 3-Arylpropynoic acids under analogous conditions gave rise to 3,3-diarylindan-1-ones, while the corresponding methyl esters were converted into methyl 3,3-diarylprop-2-enoates. The key intermediates in the transformations of acetylenic ketones and aldehydes and propargyl-type alcohols into indene derivatives are resonance-stabilized propargyl—allenyl cations -C≡ C-C⁺ ? -C⁺=C=C which reacted with one of the resonance structures to give isomeric indenes, depending on the substituent nature.     

Synthesis,spectroscopic and crystallographic characterization of the cobalt(III) ternary mixed-ligand complexes of N(4)-allyl/methyl thiosemicarbazones, <Emphasis Type="Italic">N,N,N</Emphasis>′<Emphasis Type="Italic">,N</Emphasis>′-tetramethylethylenediamine and azide

Mixed-ligand ternary cobalt(III) complexes consisting of N,N,N′,N′-tetramethylethylenediamine (tmen), R-salicylaldehyde-N(4)-allyl/methyl thiosemicarbazones (R=3-OMe (L^I/L^II) or H (L^III/L^IV) and azide, of general formula [CoL(tmen)(N₃)], were synthesized and characterized by physico-chemical and spectroscopic methods. The crystal structure of [CoL^I(tmen)(N₃)] has a slightly distorted octahedral coordination geometry involving the O, N and S atoms of thiosemicarbazone.     

An efficient approach for the synthesis of novel methyl sulfones in acetic acid medium and evaluation of antimicrobial activity

A series of nine methyl sulphones ( 3a –3 i ) starting from the aldehydes ( 1a–1i ) were synthesized in two consecutive steps. In the first step, preparation of allyl alcohols ( 2a–2i ) from their corresponding aldehydes by the reaction of sodium borohydride in methanol at room temperature is reported. Finally, methyl sulphones are synthesized by condensing sodium methyl sulfinates with allyl alcohols in the presence of BF ₃ .Et ₂ O in acetic acid medium at room temperature for about 2–3 h. The reaction conditions are simple, yields are high (85%–95%), and the products were obtained with good purity. All the synthesized compounds were characterized by their ¹ H, ¹³ C NMR, and mass spectral analysis. All the title compounds were screened for antimicrobial activity. Among the compounds tested, the compound 3f has inhibited both Gram positive and Gram negative bacteria effectively and compound 3i has shown potent antifungal activity. These promising components may help to develop more potent drugs in the near future for the treatment of bacterial and fungal infections.     

Dehydrocoupling and Diels–Alder reactions on siloxane polymers

Dehydrocoupling reactions between linear poly(methylhydrosiloxane) {Me₃SiO–[MeSi(H)O]_n–SiMe₃} and alcohols such as cholesterol, anthracene‐9‐carbinol, (12‐crown‐4)‐2‐carbinol, pyrene‐1‐carbinol, 4‐methyl‐5‐thiazoleethanol, and 4‐pyridilpropanol were introduced under catalytically mild conditions. The degrees of conversion of Si? H bonds in polysiloxane were monitored with ¹H NMR spectra. The reaction of the 9‐methoxyanthracene adduct on siloxane polymers and maleimide derivatives (maleimide, N‐ethylmaleimide, and maleic acid anhydride) produced [2+4]‐cycloadducts in very high yields. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 4013–4019, 2002     

Ketalizations of aryl ω-(2-imidazolyl)alkyl ketones by glycerol and 3-mercapto-1,2-propanediol. synthesis and characterization of cis- and trans-{2-aryl-2-[ω-(2-imidazolyl)alkyl](1,3-dioxolan-4-yl and 1,3-oxathiolan-5-yl)}methanols

Aryl 2-[(2-imidazolyl)ethyl or 3-(2-imidazolyl)propyl]ketones were ketalized by glycerol or 3-mercapto-1,2-propanediol in boiling benzene in the presence of 4-toluenesulfonic acid to provide the title compounds. The aryl substituents are 4-chloro-, 4-bromo-, 4-fluoro-, or 2,4-dichlorophenyl. While aryl (2-imidazolyl)methyl ketones condensed with glycerol to form cis- and trans-{2-aryl-2-[(2-imidazolyl)methyl]-4-(hydroxymethyl)}-1,3-dioxolanes, related condensations with 3-mercapto-1,2-propanediol, under similar, or even more stringent reaction conditions, produced no 1,3-oxathiolane analogs, with the starting ketones being recovered. Separation and structure determination of these racemic cis and trans isomeric products are described. The structure of these stereoisomers was established by means of ¹H and ¹³C nmr correlation and nOe experiments. Selective methylation of the N-unsubstituted 2-imidazolyl alcohols with one equivalent sodium hydride and methyl iodide provided the corresponding N-methyl alcohols in excellent yields. With excess benzoyl chloride, N-unsubstituted 2-imidazolyl alcohols were initially converted to O, N-dibenzoates from which the N-benzoyl group was easily cleaved by ammonium hydroxide in ethanol to provide benzoate esters.     

Synthesis and characterization of controlled drug release carriers based on functionalized amphiphilic block copolymers and super‐paramagnetic iron oxide nanoparticles

In this study, synthesis and characterization of magnetic nanocarriers are reported for drug delivery based on the amphiphilic di‐block and tri‐block copolymers of poly(ethylene glycol) (PEG) and poly(ε‐caprolactone) (PCL) with surface modified super‐paramagnetite Fe₃O₄ nanoparticles (magnetic nanoparticles (MNPs)). The synthesized block copolymers (methoxy poly(ethylene glycol) (mPEG)–PCL and PCL–PEG–PCL) were characterized by Fourier transform infrared (FT‐IR), ¹H nuclear magnetic resonance (1H NMR), gel permeation chromatography (GPC), scanning electron microscopy (SEM), and differential scanning calorimetry (DSC), and their properties such as critical micelle concentration, hydrophilicity to lipophilicity balance, and hydrolytic degradation were investigated. The block copolymers were functionalized with terminal azide groups (mPEG–PCL(N₃) and (N₃)PCL–PEG–PCL(N₃)), and magnetic Fe₃O₄ nanoparticles were surface modified with poly(acrylic acid) (PAA) and propargyl alcohol (MNP–PAA–C≡CH). Magnetic nanocarriers were synthesized by click reaction between azide‐terminated block copolymers and MNP–PAA–C≡CH and characterized by FT‐IR, thermogravimetric analysis (TGA), dynamic light scattering (DLS), vibrating sample magnetometer (VSM), and transmission electron microscopy (TEM), and cytotoxicity was investigated by methyl thiazolyl tetrazolium assay. In vitro drug loading and release and release kinetics were investigated. Copyright © 2015 John Wiley & Sons, Ltd.     

Lewis acid-catalyzed Csp3–H functionalization of methyl azaarenes with α-trifluoromethyl carbonyl compounds

A Lewis acid promoted Csp³–H bond functionalization of methyl azaarenes with α-trifluoromethylated carbonyl compounds is described. Catalytic amounts of Yb(OTf)₃ provided a straightforward access to the corresponding trifluoromethylated alcohols in excellent yields up to 94% under mild reaction conditions.     

Die Struktur des Anhydro-isocalebassin-methyläthers; Säurekatalysierte Umlagerungen des Curare-Alkaloids C-Calebassin. 60. Mitteilung über Calebassen-Alkaloide [1]

Treatment of the Calebash alkaloid C-calebassine ( 1 ), C₄₀H₄₈N₄O₂⁺⁺·2X^?, with hot mineral acid yielded the anhydro-isocalebassine acid adduct 3H , with the formula C₄₀H₄₇N₄O⁺⁺⁺·3X^?.H₂O. This was converted into anhydro-isocalebassine methyl ether salts ( 4 ) C₄₁H₄₈N₄O⁺⁺·2X^?·H₂O with alkaline dimethyl sulphate. A total X-ray analysis of the orthorhombic diiodide led to formula 4 . The conversion of C-calebassine ( 1 ) into 4 involves a radical change in the central part of the molecule. The structure of the acid adduct 3H can be deduced from the structure of 4. Treatment of 3 H with warm methanol or treatment of C-calebassine ( 1 ) with acetic acid yielded a pale yellow compound 2 , C₄₀, H₄₄N₄⁺⁺·2X^?·H₂O. The central part of the molecule 2 contains a pyrrole ring, and most probably this is an intermediate in the conversion of 1 into 3 H by mineral acid. The changes of 3 H and 2 in acidic, neutral and basic media can be shown by electronic spectroscopy. Reaction of 3 H with 1 mole of oxygen at pH 4 converted it into a stable blood-red oxidation product C₄₀H₄₄N₄O₂⁺⁺·2X^? containing a merocyanine system. The structure 7 , proposed for this compound, is discussed.     

Synthesis of AB3‐type miktoarm star polymers with steroid core via a combination of “Click” chemistry and ring opening polymerization techniques

Well‐defined AB₃‐type miktoarm star‐shaped polymers with cholic acid (CA) core were fabricated with a combination of “click” chemistry and ring opening polymerization (ROP) methods. Firstly, azide end‐functional poly(ethylene glycol) (mPEG), poly(methyl methacrylate) (PMMA), polystyrene (PS), and poly(ε‐caprolactone) (PCL) polymers were prepared via controlled polymerization and chemical modification methods. Then, CA moieties containing three OH groups were introduced to these polymers as the end groups via Cu(I)‐catalyzed click reaction between azide end‐functional groups of the polymers ( mPEG‐N₃ , PMMA‐N₃ , PS‐N₃ , and PCL‐N₃ ) and ethynyl‐functional CA under ambient conditions, yielding CA end‐functional polymers ( mPEG‐Cholic , PMMA‐Cholic , PS‐Cholic , and PCL‐Cholic ). Finally, the obtained CA end‐capped polymers were employed as the macroinitiators in the ROP of ε‐caprolactone (ε‐CL) yielding AB₃‐type miktoarm star polymers ( mPEG‐Cholic‐PCL₃ , PMMA‐Cholic‐PCL₃ , and PS‐Cholic‐PCL₃ ) and asymmetric star polymer [ Cholic‐(PCL)₄ ]. The chemical structures of the obtained intermediates and polymers were confirmed via Fourier transform infrared and ¹H nuclear magnetic resonance spectroscopic techniques. Thermal decomposition behaviors and phase transitions were studied in detail using thermogravimetric analysis and differential scanning calorimetry experiments. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 3390–3399     

H‐shaped (ABCDE type) quintopolymer via click reaction [3 + 2] strategy

H‐shaped quintopolymer containing different five blocks: poly(ε‐caprolactone) (PCL), polystyrene (PS), poly(ethylene glycol) (PEG), and poly(methyl methacrylate) (PMMA) as side chains and poly(tert‐butyl acrylate) (PtBA) as a main chain was simply prepared from a click reaction between azide end‐functionalized PCL‐PS‐PtBA 3‐miktoarm star terpolymer and PEG–PMMA‐block copolymer with alkyne at the junction point, using Cu(I)/N,N,N′,N″,N″‐pentamethyldiethylenetriamine (PMDETA) as a catalyst in DMF at room temperature for 20 h. The H‐shaped quintopolymer was obtained with a number–average molecular weight (M_n) around 32,000 and low polydispersity index (M_w/M_n) 1.20 as determined by GPC analysis in THF using PS standards. The click reaction efficiency was calculated to have 60% from ¹H NMR spectroscopy. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 4459–4468, 2008     

Synthesis and structure of lower rim C-linked tetra-N-tosyl peptidocalix[4]arenes

Chiral p-tert-butylcalix[4]arenes perfunctionalised at the lower rim with amino acid residues have been prepared. The ¹H and ¹³C NMR spectra indicate that the macrocycles adopt a cone conformation. Calix[4]arenes bearing amino acid moieties 5a shows strong complexation towards Cl⁻, Br⁻, HSO₄⁻, H₂PO₄⁻ and N-tosyl-(l)-alaninate.     

Reduced 3,4′‐bipyrazoles from a simple pyrazole precursor: synthetic sequence,molecular structures and supramolecular assembly

The reaction of 5‐chloro‐3‐methyl‐1‐phenyl‐1H‐pyrazole‐4‐carbaldehyde and N‐benzylmethylamine under microwave irradiation gives 5‐[benzyl(methyl)amino]‐3‐methyl‐1‐phenyl‐1H‐pyrazole‐4‐carbaldehyde, C₁₉H₁₉N₃O, (I). Subsequent reactions under basic conditions, between (I) and a range of acetophenones, yield the corresponding chalcones. These undergo cyclocondensation reactions with hydrazine to produce reduced bipyrazoles which can be N‐formylated with formic acid or N‐acetylated with acetic anhydride. The structures of (I) and of representative examples from this reaction sequence are reported, namely the chalcone (E )‐3‐{5‐[benzyl(methyl)amino]‐3‐methyl‐1‐phenyl‐1H‐pyrazol‐4‐yl}‐1‐(4‐bromophenyl)prop‐2‐en‐1‐one, C₂₇H₂₄BrN₃O, (II), the N‐formyl derivative (3RS )‐5′‐[benzyl(methyl)amino]‐3′‐methyl‐1′,5‐diphenyl‐3,4‐dihydro‐1′H ,2H‐[3,4′‐bipyrazole]‐2‐carbaldehyde, C₂₈H₂₇N₅O, (III), and the N‐acetyl derivative (3RS )‐2‐acetyl‐5′‐[benzyl(methyl)amino]‐5‐(4‐methoxyphenyl)‐3′‐methyl‐1′‐phenyl‐3,4‐dihydro‐1′H ,2H‐[3,4′‐bipyrazole], which crystallizes as the ethanol 0.945‐solvate, C₃₀H₃₁N₅O₂·0.945C₂H₆O, (IV). There is significant delocalization of charge from the benzyl(methyl)amino substituent onto the carbonyl group in (I), but not in (II). In each of (III) and (IV), the reduced pyrazole ring is modestly puckered into an envelope conformation. The molecules of (I) are linked by a combination of C—H…N and C—H…π(arene) hydrogen bonds to form a simple chain of rings; those of (III) are linked by a combination of C—H…O and C—H…N hydrogen bonds to form sheets of R ²₂(8) and R ⁶₆(42) rings, and those of (IV) are linked by a combination of O—H…N and C—H…O hydrogen bonds to form a ribbon of edge‐fused R ²₄(16) and R ⁴₄(24) rings.     

High-spin iron(III) complexes: structural,spectroscopic, and photochemical studies

Reaction of FeCl₃ with one equivalent of acac (acac = pentane-2,4-dionate) and KTp^Me2 (Tp^Me2 = hydrotris(3,5-dimethyl-pyrazol-1-yl)borate) yielded Tp^Me2Fe(acac)Cl (3), which upon reaction with methanolic solution of sodium azide resulted in the formation of a six coordinate compound Tp^Me2Fe(acac)N₃ (4) with a single azide. When the reaction of FeCl₃ and KTp^Me2 was performed with two equivalents of sodium azide and one equivalent of 3,5-dimethylpyrazole (Pz^Me2H), a six coordinate cis azide compound [Tp^Me2Fe(Pz^Me2H)(N₃)₂] (5) was obtained. These compounds were characterized by spectroscopic methods and single crystal X-ray crystallography. Electrochemical studies of 5 show that it can be irreversibly reduced at relatively lower potential than 4. The photolysis of 5 was performed at 77 K at different wavelengths (480, 419, and 330 nm) showing that 5 was photoreduced to a high-spin Fe(II) species instead of photooxidized to Fe(V).     

Formation of an Imino‐Stabilized Cyclic Tin(II) Cation from an Amino(imino)stannylene

The novel amino(imino)stannylene 1 was prepared by conversion of HNIPr (NIPr=bis(2,6‐diisopropylphenyl)imidazolin‐2‐imino) with one equivalent of Lappert’s tin reagent (Sn[N(SiMe₃)₂]₂). Treatment of 1 with DMAP (4‐dimethylaminopyridine) yields its Lewis acid–base adduct 2 . The reaction of 1 with one equivalent of trimethylsilyl azide results in replacement of the amino group at the tin center by an N₃ substituent with concomitant elimination of N(SiMe₃)₃ to afford dimeric [N₃SnNIPr]₂ ( 3 ). Remarkably, the reaction of 1 with B(C₆F₅)₃ produces the novel tin(II) monocation 4 ⁺[MeB(C₆F₅)₃]^? comprising a four‐membered stannacycle through methyl‐abstraction from the trimethylsilyl group.     

Synthesis of new carbamate derivatives of indole and their modification

Oximation of indoles having a methoxycarbonylamino group on C⁵ and an acyl group on C³ with hydroxylamine hydrochloride in the presence of pyridine gave the corresponding oximes. The reduction of the 3-C=O group with sodium tetrahydridoborate in the presence of sodium hydroxide was accompanied by removal of the methoxycarbonyl group at the pyrrole nitrogen atom with formation of racemic alcohols. 1,4-Addition of 1-(pyridin-3-yl)butane-1,3-dione to dimethyl 1,4-benzoquinone diimine N,N′-dicarboxylate in dioxane in the presence of sodium methoxide, followed by heating in boiling 22% hydrochloric acid, afforded methyl 2-methyl-5-(methoxycarbonylamino)-3-(pyridin-3-ylcarbonyl)-1H-indole-1-carboxylate. 3-(Dimethylamino)-1-(4-methyl-1,2,5-oxadiazol-3-yl)prop-2-en-1-one reacted with N,N′-bis(methoxycarbonyl)- and N,N′-bis(phenylsulfonyl)-1,4-benzoquinone diimines in methylene chloride and acetic acid, respectively, in the presence of BF₃ · Et₂O to produce indoles having a 1,2,5-oxadiazolylcarbonyl group on C₃.