A direct synthesis of α-(hydroxymethyl) and α-alkyl-vinyl alkyl ketones

Reaction of 2,4-diketoesters 3a-c with aqueous formaldehyde using potassium carbonate solution as base affords the corresponding α-methylene-β-hydroxyalkanones 4a-c which provide a route to α,β-unsaturated alkyl ketones 6a-e via coupling of α-acetoxymethyl alkyl vinyl ketone 5a with Grignard reagents in the presence of a catalytic amount of LiCuBr₂ at low temperature.     

Aluminum and zinc complexes supported by functionalized phenolate ligands: Synthesis, characterization and catalysis in the ring-opening polymerization of ε-caprolactone and rac-lactide

A series of aluminum and zinc complexes supported by functionalized phenolate ligands were synthesized and characterized. Reaction of 2-(3,5-R₂C₃N₂)C₆H₄NH₂ (R = Me, Ph) with salicylaldehyde or 3,5-di-tert-butylsalicylaldehyde afforded 2-((2-(1H-pyrazol-1-yl)phenylimino)methyl)phenol derivatives 2a-2d. Treatment of 2a-2d with an equiv. of AlR²₃ (R² = Me, Et) gave corresponding aluminum aryloxides 3a-3e, while reaction with an equiv. of ZnEt₂ afforded zinc aryloxides 4a-4d. Treatment of 2c with 0.5 equiv. of ZnEt₂ formed diphenolato zinc complex 5. All new compounds were characterized by ¹H and ¹³C NMR spectroscopy and elemental analyses. The structures of complexes 3a, 4a and 5 were further characterized by single crystal X-ray diffraction techniques. The catalytic activity of complexes 3-5 toward the ring-opening polymerization of ε-caprolactone was studied. The zinc complexes (4a-4d) exhibited higher catalytic activity than the aluminum complexes (3a-3e). The diphenolato zinc complex 5 showed lower catalytic activity than the ethylzinc complexes 4a-4d. The aluminum complex (3b) is inactive to initiate the ROP of rac-lactide, while the zinc complex (4d) is active initiator for the ROP of rac-lactide, giving atactic polylactide.     

Synthesis and characterization of titanium alkyl, oxo, and diene complexes bearing a SiMe2-bridged phenoxy-cyclopentadienyl ligand and their catalytic performance for copolymerization of ethylene and 1-hexene

A series of titanium complexes bearing a SiMe₂-bridged phenoxy-cyclopentadienyl ligand were synthesized and characterized, and their catalytic behavior for copolymerization of ethylene and 1-hexene was investigated. Treatment of dimethylsilyl(2,3,4,5-tetramethylcyclopentadienyl)(3-tert-butyl-5-methyl-2-phenoxy)-titanium dichloride (1) with appropriate nucleophiles afforded dimethoxy complex 2, dimethyl complex 3, and dibenzyl complex 4. Standing a toluene solution of 2 in air afforded a dinuclear μ-oxo complex 5 as a single isomer. 1,3-Diene complexes 6-8 were prepared by reaction of 1 with the corresponding 1,3-dienes in the presence of 2 equiv. of n-BuLi. X-ray analysis of 1,4-diphenyl-1,3-butadiene complex 6 revealed that the diene ligand coordinates to titanium in s-cis fashion with a prone orientation. The newly prepared titanium complexes were applied to copolymerization of ethylene and 1-hexene upon activation with AlⁱBu₃ and [C₆H₅NMe₂H][B(C₆F₅)₄]. It was found that the alkyl complexes 3-4 and the diene complexes 6-8 showed higher activities than 1 at elevated temperature.     

Preparation of glycoluril monomers for expanded cucurbit[n]uril synthesis

Glycoluril derivatives bearing free ureidyl groups (1) and bis(cyclic ethers) (2) are the fundamental building blocks for the synthesis of cucurbituril, its derivatives, and its congeners. The known derivatives of 1 and 2 fall into two main classes—those bearing alkyl or aryl functional groups on their convex face. In this paper we present a third class of glycolurils, namely those bearing substituents that are electron withdrawing in character. This class of compounds carries carboxylic acid derived functional groups on their convex face and are derived from diesters 1e and 2e. An improved synthesis of 1e and 2e is reported and their modification described. For example, 1e and 2e are converted into secondary amides (10-15) by heating in solutions of the neat primary amines. The secondary amides can be transformed into imides (19-22, 24, 25) by heating with PTSA in ClCH₂CH₂Cl. The isolation of these compounds in pure form in high yields is accomplished by simple and scalable washing or recrystallization procedures. We also present the X-ray crystallographic characterization of bis(cyclic ethers) 2e, 8, and 22. We anticipate that the ready availability of ester, carboxylate, acid, secondary amide, imide, and tertiary amide derivatives of 1 and 2 will expand the scope of the synthesis of cucurbituril derivatives by providing a new class of building blocks with electron withdrawing substituents.     

Rearrangement of fused tetracyclic heterocycles induced by alkyl halides and formation of a new type of ‘proton sponge’

Intramolecular criss-cross cycloaddition of 3-substituted symmetrical homoallenyl azines 2 by heating in xylene lead to interesting fused heterocyclic systems consisting of four five-membered rings with two nitrogen atoms in the skeleton 3. These compounds 3 were found to be sensitive to attack by alkyl halides. Their presence, depending on the reaction conditions, resulted in a new type of rearrangement leading to compounds 4 and 5, respectively. With an excess of alkyl halide and in the presence of NaBH₃CN a new structure 6 with signs of the molecule corresponding a ‘proton sponge’ moiety was created. The scope of the rearrangement and reaction products structure was investigated.     

Structure and reactivity of mono- and dinuclear diiminate zinc alkyl complexes

The synthesis, structure and reactivity of several diiminate ligands are presented. The syntheses of five representative β-diiminate (BDI) zinc alkyl complexes and one β-oxo-δ-diiminate (BODDI) zinc alkyl are described. BDI ligands with varying backbone and N-aryl substituents display different solid state structures. [(BDI)ZnR] are synthesized by the reaction of (BDI)H with ZnR₂ in quantitative yield. Previously reported (BDI-1)ZnEt is a three-coordinate monomer in the solid state whereas [(BDI-3)ZnEt]_∞ [(BDI-3)=2-((2,6-diisopropylphenyl)amido)-3-cyano-4-((2,6-diisopropylphenyl)imino-2-pentene] and [(BDI-4)ZnEt]_∞ [(BDI-4)=2-((2,6-diethylphenyl)amido)-3-cyano-4-((2,6-diethylphenyl)imino-2-pentene] form one dimensional coordination polymers. The bimetallic complex [(BODDI-1)(ZnEt)₂] [(BODDI-1)=2,6-bis((2,6-diisopropylphenyl)amido)-2,5-heptadien-4-one] is prepared through the reaction of (BODDI-1)H₂ with two equivalents ZnEt₂. Both [(BDI)ZnEt] and [(BODDI)ZnEt] complexes react with acetic acid to give the acetate complexes in moderate to high yields, offering a superior synthetic route to these complexes. [(BDI)ZnR] [BDI=(BDI-3) or 1,1,1-trifluoro-2-((2,6-diisopropylphenyl)amido)-4-((2,6-diethylphenyl)imino-2-pentene), (BDI-5)] complexes react with MeOH to produce [{(BDI)Zn(μ-OMe)}₂Zn(μ-OMe)₂] in moderate yields. The molecular structures of [(BDI-3)ZnEt], [(BDI-4)ZnEt], [(BODDI-1)(ZnEt)₂], [(BODDI-1)Zn₂(μ-OAc)₂], [{(BDI-3)Zn(μ-OMe)}₂Zn(μ-OMe)₂] and [{(BDI-5)Zn(μ-OMe)}₂Zn(μ-OMe)₂] have been determined by X-ray diffraction.     

Synthesis of D-mannitol substituted ether-linked bis-1,2,3-triazoles as models of gemini surfactants

Readily available and low cost D-mannitol was converted into 1,2,5,6-di-O-isopropylidene-D-mannitol (1) in the presence of acetone and zinc chloride. Williamson etherfication of 1 with propargyl bromide afforded the bisalkyne 2 in a very good yield. 1,3-Dipolar cycloaddition of 2 with four different alkyl azides using click conditions gave four novel bistriazoles 3a-d. Removal of the acetal groups of 3a-d afforded the deprotected bistriazoles 4a-d in excellent yields. Products 3 and 4 represent models of gemini surfactants.     

Addition of 2-tert-butyldimethylsilyloxythiophene to activated quinones: an approach to thia analogues of kalafungin

The uncatalyzed reaction of 2-tert-butyldimethylsilyloxythiophene 2 with 1,4-quinones bearing either an electron withdrawing acetyl or a carbomethoxy group at C-2, was investigated. No reaction was observed using 1,4-quinones 8 and 9 bearing an ester group at C-2 whereas use of 1,4-quinones 10 and 11 bearing an acetyl group at C-2 only provided low yields of the silyloxythiophenes 15 and 16 resulting from electrophilic substitution of the silyloxythiophene by the 1,4-quinone. Use of the Lewis acids InCl₃, Cu(OTf)₂ and BF₃·Et₂O were investigated in an effort to improve the yield of the desired annulation reaction. BF₃·Et₂O proved to be the optimum catalyst for the synthesis of thiolactone naphthofuran adducts 14 and 18 from 1,4-naphthoquinones 9 and 11, respectively. Reaction of 2-tert-butyldimethylsilyloxythiophene 2 with 1,4-benzoquinones 8 and 10 bearing a carbomethoxy or an acetyl group at C-2, respectively, afforded thiolactone benzofuran adducts 13 and 17, respectively, catalyzed by either InCl₃ or Cu(OTf)₂. Addition of 2-tert-butyldimethylsilyloxythiophene 2 to 3-acetyl-5-methoxy-1,4-naphthoquinone 12 afforded adduct 19 that underwent oxidative rearrangement to thiolactone pyranonaphthoquinone 20 using ceric ammonium nitrate in acetonitrile, thus providing a novel approach for the synthesis of a thia analogue of the pyranonaphthoquinone antibiotic kalafungin.     

Facile synthesis of 4-phenylquinolin-2(1H)-one derivatives from N-acyl-o-aminobenzophenones

An efficient synthesis of 4-phenylquinolin-2(1H)-one derivatives has been achieved in a one-pot reaction from N-acyl-o-aminobenzophenones 1a-c (a: acyl=acetyl; b: acyl=propanoyl; c: acyl=heptanoyl) using NaH as a base. Treatment of 1 with NaH provided the quinolones 2a-c with 62-83% yields, whereas the reaction in the presence of alkyl iodide (alkyl=methyl, ethyl, n-octyl) gave the corresponding N-alkylated quinolones 3a-g in 75-95% yields. The alkylation reaction of 4-phenylquinolin-2(1H)-one 2a with alkyl halide gave a mixture of N-alkylated and O-alkylated products. Comparison of IR and NMR data of the N-alkylated and O-alkylated compounds with those of 2a-c indicated that 2a-c exist as the lactam form.     

Synthesis of Closo-1,7-Carboranyl Alkyl Amines

Of the three closo-carborane isomers (C₂B₁₀H₁₂), closo-1,2-carborane has been used most widely in the synthesis of carboranyl amines. However, closo-1,2-carboranes are prone to deboronation to nido-7,8-carborane under various conditions including attack by basic amino groups. In order to overcome this problem, closo-1,7-carboranyl ethyl-, propyl-, and butylamine were synthesized, which should be more stable towards basic deboronation than their closo-1,2-carboranyl counterparts. These closo-1,7-carboranyl amines (5, 18 and 19) were synthesized using two different methods, both starting from the corresponding closo-1,7-carboranyl alkyl iodides (3, 14 and 15). One of the carboranyl alkyl amine (5) was conjugated with folic acid to form a closo-1,7-carborane-folic acid bioconjugate (20).     

A novel procedure for the preparation of zinc reagents: a practical synthesis of (+)-biotin

The use of bromine for activation of zinc dust allowed smooth and reproducible reduction of iodide 1 to the corresponding zinc reagent 2. The zinc reagent 2 obtained by the present protocol was allowed to the Fukuyama coupling reaction with thiolactone 3 to provide a key intermediate 4 for (+)-biotin in high yield using a reasonably fair amount of 1 (1.4 equiv).     

Microwave-assisted synthesis of novel bis(2-thioxothiazolidin-4-one) derivatives as potential GSK-3 inhibitors

(5Z,5′Z)-3,3′-(1,4-Phenylenebis(methylene)-bis-(5-arylidene-2-thioxothiazolidin-4-one) derivatives (5a-r) have been synthesized by the condensation reaction of 3,3′-(1,4- or 1,3-phenylenebis(methylene))bis(2-thioxothiazolidin-4-ones) (3a,b) with suitably substituted aldehydes (4a-f) or 2-(1H-indol-3-yl)2-oxoacetaldehydes (8a-c) under microwave conditions. The bis(2-thioxothiazolidin-4-ones) were prepared from the corresponding primary alkyl amines (1a,b) and di-(carboxymethyl)-trithiocarbonyl (2). The 2-(1H-indol-3-yl)-2-oxoacetaldehydes (8a-c) were synthesized from the corresponding acid chlorides (7a-c) using HSnBu₃.     

Zn-promoted regio- and sequence-selective one-pot joining reactions of three components: vinylpyridines, alkyl iodides, and carbonyl compounds (or nitriles)

Addition of alkyl iodides (3) into the solution containing 2-(or 4-)vinylpyridine (1 or 2) and carbonyl compounds (6) in the presence of Zn-powder (99.9%) in acetonitrile under refluxing brought about regio- and sequence-selective joining reaction of three components to give the corresponding (2-hydroxyethyl)pyridines (7 or 8) in good to moderate yields. On the other hand, 2-(2- or 4-pyridyl)ethyl alkyl ketones (10 or 11) were obtained from the similar joining reaction of three components by addition of alkyl iodides (3) into the solution of 2-(or 4-)vinylpyridine (1 or 2), and nitriles (9) in toluene containing Zn-powder (99.9%) under the similar reaction conditions.     

Oxidation of sulfides with hydrogen peroxide catalyzed by synthetic flavin adducts with dendritic bis(acylamino)pyridines

The catalytic activities of the cationic synthetic flavin adduct 1 with various dendritic and non-dendritic 2,6-bis(acylamino)pyridines 2 were examined for the oxidation of organic sulfides with H₂O₂. The adduct of 5-ethyllumiflavinium perchlorate 1a with 2b–d bearing poly(benzyl ether) dendron units acts as an efficient organocatalyst for the oxidative transformation of sulfides to the corresponding sulfoxides under mild conditions.     

An expedient, regioselective synthesis of 2-alkylamino- and 2-alkylthiothiazolo[5,4-e]indoles

1-Benzenesulfonyl-5-aminoindole 5, prepared from 5-nitroindole 3, was condensed with alkyl isothiocyanates and separately with carbon disulfide and alkyl bromides/iodides to furnish efficiently the corresponding N-alkyl-thioureidoindoles 6a-c and the alkyl N-(indol-5′-yl)dithiocarbamates 9a-e, respectively. Their cyclisation using N-bromosuccinimide (NBS) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), in the cold, followed by indolic N-deprotection, furnished regioselectively the 2-alkylamino- and the 2-alkylthiothiazolo[5,4-e]indoles 8a-c and 11a-e, respectively, in good overall yields.     

Informative secondary chiroptics in binary molecular organogel systems for donor-acceptor energy transfer

Pyrene-doped l-glutamide-based lipidic derivatives with different alkyl lengths (C_n-g-Pyr; n = 4, 8 and 12) were newly synthesized. All of the C_n-g-Pyr dissolved and showed thermotopically and lyotropically-induced excimer formations accompanied by induction of the positive Cotton effect in their CD spectra, indicating chirally ordered stacking. However, when C₄-g-Pyr and C₁₂-g-Pyr were mixed in a certain molar ratio, an unusual CD pattern from positive to negative ones was observed. In this study, energy transfer efficiency was investigated in a binary system of C_n-g-Pyr with C₁₂-g-TPP. The results revealed that simple modification of the alkyl length of C_n-g-Pyr enables enhancement of the energy transfer efficiency with C₁₂-g-TPP.     

Pyrrolide-imine benzyl complexes of zirconium and hafnium: synthesis, structures, and efficient ethylene polymerization catalysis

A series of pyrrolyl-imines HL^1-6 was prepared by the condensation of pyrrole-2-carboxyaldehyde with different amines. The reaction of 2 equiv of pyrrolyl-imine with tetrabenzyl complexes of hafnium and zirconium M(CH₂Ph)₄ (M=Hf or Zr) gave dibenzyl complexes (L^3-6)₂M(CH₂Ph)₂, which were characterized by NMR spectroscopy and crystal structure analysis. NMR spectra of the complexes with secondary alkyl substituents at the imine nitrogen (isopropyl: 3a, 4-tert-butylcyclohexyl: 4a and 4b) suggest that rapid racemization between Δ and Λ configurations occurs in solution on the NMR time scale. The complexes with pyrrolide-imine ligands with a tertiary alkyl group such as tert-butyl (5a and 5b) or 1-adamantyl (6a and 6b) at the imine nitrogen possess cis-configured benzyl groups. Hafnium complexes 5a and 6a react with B(C₆F₅)₃ in bromobenzene-d₅ to give the corresponding cationic benzyl complexes, which exhibit high activity for ethylene polymerization (5a: 2242 kg-polymer/ mol-Hf h bar, 6a: 2096 kg-polymer/ mol-Hf h bar). Zirconium complexes 5b and 6b display a remarkably high ethylene polymerization activity when activated with methylaluminoxane (5b: 17,952 kg-polymer/mol-Zr h bar, 6b: 22,944 kg-polymer/mol-Zr h bar).     

The synthesis of 2,4-dienyl fluoroalkyl ketones by a tandem three-stage sequence of propargyl 2-fluoroalkylvinyl ether formation, Claisen rearrangement, and allene-to-conjugated diene isomerization

A tandem three stages process to a series of trifluoromethyl and halodifluoromethyl 2,4-unsaturated ketones 4a-c is described. This process started with the preparation of 2-fluoroalkyl substituted propargyl vinyl ether 3a-d by treatment of a mixture of individual ethyl α-per(poly)fluoroalkyl acetates 1a-d and propargyl alcohol 2 in CH₂Cl₂ with the mixed base (Na₂CO₃/TEA) at ambient temperature. When heated in toluene at 80°C, these ethers readily underwent a tandem propargyl-allenyl Claisen rearrangement and isomerization of the resultant 3,4-dienone to give 2,4-unsaturated fluoroalkyl ketones 4a-c (Z/E mixture). The reaction of ethyl α-per(poly)fluoroalkyl acetate 1 with 1-phenyl propargyl alcohol 5 in refluxing CH₂Cl₂ in the presence of the mixed base (Na₂CO₃/TEA) directly afforded the corresponding unsaturated fluoroalkyl ketone 6a-c in one pot. In the presence of NaH, the reaction of ethyl 3-halo-3-fluoroalkylacrylates 8a-b with 1,1-dimethyl propargyl alcohol 9 at −50°C to 0°C also gave the unsaturated fluoroalkyl ketones 10a-b in one pot. The difluorovinyl propargyl ether 11 produced by reduction of 2-bromodifluoromethyl substituted propargyl vinyl ether 3b rearranged in hot benzene to give the corresponding allene 12 bearing a gem-difluoromethylene group in the middle of the aliphatic chain.     

Light-harvesting composites of directly connected porphyrin-phthalocyanine dyads and their coordination dimers

Directly linked porphyrin (Por)-phthalocyanine (Pc) heterodyads (H₂Por-H₂Pc and H₂Por-ZnPc) with an imidazolyl group at porphyrin’s meso-position were synthesized. Introduction of a zinc ion into the porphyrin afforded stable complementary dimers of the heterodyads. The heterodyads and their dimers gave extensive and strong absorption bands owing to the porphyrin and phthalocyanine components and induced an efficient energy transfer from porphyrin to phthalocyanine. Strong fluorescence from phthalocyanine was observed in the case of H₂Por-H₂Pc.     

Ionic liquid phase organic synthesis (IoLiPOS) methodology applied to the three component preparation of 2-thioxo tetrahydropyrimidin-4-(1H)-ones under microwave dielectric heating

An ionic liquid phase organic synthesis (IoLiPOS) has been developed for the preparation of 2-thioxo tetrahydropyrimidin-4(1H)-ones. Treatment of the starting poly(ethyleneglycol)ionic liquid phases (PEG_n-ILPs) 1 with acryloyl chloride 2 afforded a serie of (PEG_n)-ILPs bound acrylate 3 in quantitative yields. Michael addition of aliphatic primary amines 5 to the PEG₁-ILPs 3(a,d) allowed the preparation of β-aminoesters 6 in high yields. Addition of alkyl isothiocyanates 7 to 6 gave the corresponding thioureido esters 8 in the third step. The final cyclization-cleavage under microwave/solventless strategy provides, under basic conditions, the expected 2-thioxo tetrahydropyrimidin-4(1H)-ones 9 in high purity after flash chromatography. According to the IoLiPOS methodology, the NMR method was used to establish loading of all the PEG-ionic liquid phases intermediates.