Phase-Transfer-Catalyzed Michaelis-Becker Synthesis of Dialkyl Methyl Phosphonates

A liquid–liquid phase-transfer-catalyzed (PTC) Michaelis-Becker reaction was adopted in the preparation of dialkyl methyl phosphonate (R = Me, iPr, nBu, and iBu). This was performed by the reaction of an appropriate dialkyl hydrogen phosphonate with methyl iodide in the presence of benzyl triethyl ammonium chloride and sodium hydroxide as PTC and base, respectively. A liquid–liquid two-phase system (H₂O/CH₂Cl₂) introduced a suitable situation for the preparation of dialkyl methyl phosphonates with bulky alkyl groups (R = iPr, nBu, and iBu), but with R = Me, the hydrolysis of dimethyl hydrogen phosphonate (reagent) reduced the yield to 22%. In this case, a solid–liquid PTC-free system was successfully applied and yield of over 80% was obtained.     

Phosha-Meerwein Reaction of Diazo Esters

Abstract

Diazo esters (la,b) react with trialkyl phosphates (2a–c) in the presence of BF₃.OEt₂ to give the corresponding phosphates (3a–e) in 42–58 % yields. The competed intra/intermolecular protonation in the reaction of la with dimethyl hydrogen phosphite leads to phosphonate. 4,and phosphite 5.     

Synthesis of S-(28a-homobetulin-28a-yl) thiophosphate,thiophosphonate, and thiophosphinate

A concise synthesis of thiophosphate, phenylthiophosphonate, and diphenylthiophosphinate esters bearing a 28a-homolupane residue is reported. The new triterpenes were obtained from the readily available 3-O-acetylichopanol by a nucleophilic substitution of the corresponding mesylate with thiocyanate ion followed by a Michaelis–Arbuzov reaction. These results open the way to new lupane-type derivatives having a thiophosphorus moiety at the lupane core as potential anticancer compounds. Additionally, the cytotoxic activities of the new homolupane compounds were evaluated in vitro.     

Substrate- and temperature-controlled divergence in reactions of alcohols with TosMIC catalyzed by BF3 · Et2O: Facile access to sulfinates and sulfones

An efficient BF₃?·?Et₂O-catalyzed divergent synthesis of sulfinate esters and sulfones through C–O and C–S bond formation has been achieved from alcohols and p-toluenesulfonylmethyl isocyanide (TosMIC). Various alcohols reacted smoothly with TosMIC under the present conditions at room temperature providing sulfinate esters exclusively. By tuning the reaction temperature, the alcohols that provide highly stabilized carbocation in the reaction medium afforded sulfones as sole products. This study was aimed at understanding the regioselectivity of ambidentate sulfinate ion and to elucidate the interpretation of sulfinate/sulfone scaffolds.     

Task-Specific Ionic Liquid as Reagent and Reaction Medium for the One-Pot Horner–Wadsworth–Emmons–Type Reaction Under Microwave Irradiation

A task-specific imidazolium-based phosphinite ionic liquid (IL-OPPh₂) was used as the dual solvent–reagent for the synthesis of E-cinamates and coumarin derivatives via the one-pot Horner–Wadsworth–Emmons–type reaction. The ionic liquid containing its corresponding phosphinite moiety was reacted with α-chloro esters and benzaldehyde or salicylaldehyde derivatives in the presence of sodium methoxide under microwave irradiation to produce the related E-cinamates or coumarins, respectively. The satisfactory results were obtained with good yields, short reaction time, and simple experimental procedure.     

Organogelation and cytotoxic evolution of phosphonate ester functionalised hydrophobic alkanediamide motifs

Here we report various rigid alkanediamide derivatives, with three different substitution patterns of phosphonate ester for investigation of organogelation properties. The gelation properties of these compounds can be tuned by altering the number and position of the phosphonate esters. It was found that supramolecular self-assembly of the bisphosphonate esters (1a, 1d, 1h and 2a–b) resulted gel formation, whereas that of the tetraphosphonate esters (3a, 3d, 3h) resulted in construction of nanospheres and microspheres. The diverse morphology of the gel formation appears to depend predominantly on the substituted phenyl ring of the phosphonate ester functionality. Subsequent in vitro cytotoxic screening against four human tumour cell lines (A549, MDA-MB-231, MCF-7 and HeLa) using MTT assays revealed that derivatives 1f–h and 3a show cytotoxic potencies at concentrations less than 5 μM (IC₅₀ values). Compounds 1f–h exhibited promising activity against A549 cell line, 1g–h were highly effective against MDA-MB-231, 1f and 3a show potential against MCF-7 and 1f–g were active against the HeLa cell line.     

“Instant Methylide” Modification of the Corey–Chaykovsky Epoxide Synthesis

Abstract

We report that Me₃S(O)⁺I^? (1) and Me₃S⁺I^? (2) form stable, dry mixtures with KOt-Bu and NaH, respectively, which remain stable upon prolonged storage (>1 year). The corresponding methylides (Me₂SO=CH₂ and Me₂S=CH₂) are generated upon addition of DMSO or DMSO/THF solutions of carbonyl compounds, cleanly affording epoxides via the Corey–Chaykovsky reaction in good yields and short reaction times (as short as 20 min when 1–2 mmol of various ketones and aldehydes were treated with a mixture of 1 and KOt-Bu at 50–60°C).     

Reticular Chemistry of Uranyl Phosphonates: Sterically Hindered Phosphonate Ligand Method is Significant for Constructing Zero-Dimensional Secondary Building Units

Designability is an attractive feature for metal–organic frameworks (MOFs) and essential for reticular chemistry, and many ideas are significantly useful in the carboxylate system. Bi-, tri-, and tetra-topic phosphonate ligands are used to achieve framework structures. However, an efficient method for designing phosphonate MOFs is still on the way, especially for uranyl phosphonates, owing to the complicated coordination modes of the phosphonate group. Uranyl phosphonates prefer layer or pillar-layered structures as the topology extension for uranyl units occurs in the plane perpendicular to the linear uranium-oxo bonds and phosphonate ligands favor the formation of compact structures. Therefore, an approach that can construct three-dimensional (3D) uranyl phosphonate MOFs is desired. In this paper, a sterically hindered phosphonate ligand method (SHPL) is described and is successfully used to achieve 3D framework structures of uranyl phosphonates. Four MOF compounds ([AMIM]₂(UO₂)(TppmH₄) ⋅ H₂O ( UPF-101 ), [BMMIM]₂(UO₂)₃(TppmH₄)₂ ⋅ H₂O ( UPF-102 ), [Py14]₂(UO₂)₃(TppmH₄)₂ ⋅ 3 H₂O ( UPF-103 ), and [BMIM](UO₂)₃(TppmH₃)F₂ ⋅ 2 H₂O ( UPF-104 ); [AMIM]=1-allyl-3-methylimidazolium, [BMMIM]=1-butyl-2,3-dimethylimidazolium, [Py14]=N-butyl-N-methylpyrrolidinium, and [BMIM]=1-butyl-3-methylimidazolium) are obtained by ionothermal synthesis, with zero-dimensional nodes of uranyl phosphonates linked by steric tetra-topic ligands, namely tetrakis[4-(dihyroxyphosphoryl)phenyl]methane (TppmH₈), to give 3D framework structures. Characterization by PXRD, UV/Vis, IR, Raman spectroscopy, and thermogravimetry (TG) were also performed.     

A sequential reaction process to assemble polysubstituted indolizidines, quinolizidines and quinolizidine analogues

The ω-iodo-α,β-alkynoates and their ketone, sulfone or phosphonate analogues react with δ-chloropropylamines in MeCN assisted with K₂CO₃ to undergo a sequential S_N2/Michael addition/S_N2/S_N2 reaction process, giving polysubstituted indolizidines or quinolizidines in good to excellent yields. This sequential reaction process is also compatible with three other substituted α,β-alkynoates, affording quinolizidine analogues in moderate to good yields.     

Chemoselectivity Control in the Asymmetric Hydrogenation of γ‐ and δ‐Keto Esters into Hydroxy Esters or Diols

The asymmetric hydrogenation of aromatic γ‐ and δ‐keto esters into optically active hydroxy esters or diols under the catalysis of a novel DIPSkewphos/3‐AMIQ–Ru^II complex was studied. Under the optimized conditions (8 atm H₂ , Ru complex/t‐C₄H₉OK=1:3.5, 25 °C) the γ‐ and δ‐hydroxy esters (including γ‐lactones) were obtained quantitatively with 97–99 % ee. When the reaction was conducted under somewhat harsh conditions (20 atm H₂ , [t‐C₄H₉OK]=50 mm , 40 °C), the 1,4‐ and 1,5‐diols were obtained predominantly with 95–99 % ee. The reactivity of the ester group was notably dependent on the length of the carbon spacer between the two carbonyl moieties of the substrate. The reaction of β‐ and ?‐keto esters selectively afforded the hydroxy esters regardless of the reaction conditions. This catalyst system was applied to the enantioselective and regioselective (for one of the two ester groups) hydrogenation of a γ‐?‐diketo diester into a trihydroxy ester.     

“Instant Methylide” Modification of the Corey–Chaykovsky Cyclopropanation Reaction

Treatment of various electron‐deficient alkenes in DMSO with stable, dry, equimolar mixtures of either Me₃S(O)I/KOt‐Bu or Me₃S(O)I/NaH cleanly afforded the corresponding substituted cyclopropanes in good yields and short reaction times (<20 min for reactions at 50–60°C using 0.4–4.0 mmol alkene).     

CuI–Ionic Liquids as Efficient Reaction Media for the Synthesis of Pyran Skeleton via Domino Knoevenagel–Hetero–Diels–Alder Reaction with Unactivated Alkynes

The article describes ionic liquids [bmim][NO₃] in the presence of 30% mol CuI as efficient media for the domino Knoevenagel–hetero–Diels–Alder reaction of o-propargyloxy benzaldehydes as unactivated terminal alkynes with some active methylene compounds. Short reaction time, easy workup, good to excellent yields, and mild conditions are advantages of this new media.

Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.     

Synthesis of Some New Triphenylphosphanylidenes,Alkylphosphonates, and Heterocycles of Pyrazole Derivatives and Their Antimicrobial Activity

Abstract

The reaction of 5(4H)-pyrazolone with phosphorus ylides afforded new triphenylphosphanylidene alkanone derivatives. Moreover, its benzylidene derivative reacted with Wittig–Horner reagents to give the corresponding dialkoxyphosphoryl, alkyl phosphonate, and heterocyclic products. Treatment of pyrazole-4-carbaldehyde with Wittig–Horner reagents and trialkyl phosphites gave the respective alkyl phosphonate adducts. Mechanisms accounting for the formation of the new products are discussed. The biological activity of some of the newly synthesized compounds was also examined.     

Catalase-like catalytic reaction of the dinuclear manganese–salen complex

Catalase-like activity of a dinuclear manganese-salen (Mn–salen) complex, [Mn(salen)(H₂O)]₂(ClO₄)₂ (salen = N,N ′-bis(salicylidene)-1,2-diaminoethane), was investigated. The dinuclear Mn–salen complex exhibits higher catalase-like activity than that of the mononuclear Mn–salen compound, and its activity can be enhanced by an external base. Different reaction intermediates in the presence and absence of an external base were observed, and the catalytically active species was dimeric as evidenced by UV-Vis spectroscopic studies and mass spectrometry data.     

Poly‐(p‐phenylene vinylenes) with pendent 2,4‐difluorophenyl and fluorenyl moieties: Synthesis,characterization, and device performance

To improve efficiency, processability, and stability, three novel poly‐(p‐phenylene vinylenes) (PPVs) derivatives ( P _a , P _b , and P _c ) with pendent 2,4‐difluorophenyl and fluorenyl moieties were synthesized via Gilch reaction. Their structures were characterized by ¹H NMR, ¹³C NMR, and ELEM. ANAL . Compared with those of PPV and MEH‐PPV, the absolute quantum efficiencies of these polymers showed remarkable improvement (measured at 38.7, 37.2, and 20.3%, respectively), which can be attributed to the presence of twisted multiaryl segments and fluorine atoms. TGA revealed that the inflection temperatures of their thermal decomposition curves were above 400 °C. Double‐layered electroluminescent devices with these polymers as light‐emitting layers [ITO/PEDOT:PSS/Polymer/Ba/Al] showed peak emissions at 493/515, 503, and 600 nm and maximum luminance of 2700, 450, and 4700 cd/m² for P _a , P _b , and P _c , respectively, with onset voltages of ～4 V. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 2500–2508, 2009     

Organocatalytic Enantioselective Mukaiyama–Mannich Reaction of Isatin-Derived Ketimines for the Synthesis of Oxindolyl-β3, 3-Amino Acid Esters

Mukaiyama–Mannich reactions of ester enolate equivalents with aldimines have been elegantly used for the asymmetric synthesis of β-amino acids; nevertheless, the corresponding asymmetric reaction employing ketimines are unexplored. Herein, the first organocatalytic enantioselective Mukaiyama–Mannich reaction employing isatin-derived ketimines with unsubstituted silyl ketene acetals is disclosed towards the scalable synthesis of 2-oxoindolinyl-β^{3, 3}-amino acid esters at room temperature with excellent enantioselectivities (ee >99.5 %). Ultra-low catalyst loadings (as low as 250 ppm) could be used for the quantitative product formation with high enantiopurity. The synthetic utility of this protocol has been showcased in the short formal synthesis of pharmaceutically demanded (+)-AG-041R, a potent gastrin/CCK-B receptor antagonist.     

Synthesis of a New Phosphonate Methacrylate Monomer

In this work, a new methacrylate phosphonate monomer synthesis was described according to a two-step reaction. First the monoaddition of thioglycolic acid onto dimethylvinyl phosphonate monomer led to dimethyl–5-carboxymethyl-2-thiaethylphosphonate, a new phosphonate acid compound. This reaction also led to the thioester homologue of dimethyl–5-carboxymethyl-2-thiaethylphosphonate with a 15% yield by reaction of a thioglycolic acid thioester with dimethylvinyl phosphonate. Second, dimethyl carboxy-4-thia-butyl phosphonate reacted with glycidyl methacrylate. This epoxy-acid addition reaction was catalyzed by chromium salt at 70°C and led to the new methacrylate phosphonate monomer. We showed that only the secondary alcohol was obtained via a β addition. The two-step reaction final yield was calculated to be about 85%.     

P and H NMR studies of the transesterification polymerization of polyphosphonate oligomers

Polymeric phosphonate esters are an interesting class of organophosphorus polymers because both the polymer backbone and phosphorus substituents can be modified. These polymers have been prepared by ring-opening polymerizations of cyclic phosphites, stoichiometric polycondensations of dimethyl phosphonate with diols in conjunction with diazomethane treatment and by transesterification of polyphosphonate oligomers. Our initial attempts to prepare high molecular weight polymeric phosphonate esters by the transesterification methods were unsuccessful. Results indicate that the reactions of dimethyl phosphonate with diols to form polyphosphonate oligomers with only methyl phosphonate end groups are plagued by a serious side reaction that forms phosphonic acid end groups. These end groups do not participate in the transesterification reaction and limit the molecular weights of the polymers that can be obtained. The phosphonic acid end groups can be converted into reactive methyl phosphonate end groups by treatment with diazomethane, however diazomethane is explosive and the polymerization is slow. An alternative route for the production of high molecular weight polymers is the transesterification of the 1,12-bis(methyl phosphonato)dodecane, formed by the reaction of excess dimethyl phosphonate and 1,12-dodecanediol, with a Na₂CO₃ promoter. This allows polymers with molecular weights of up to 4.5×10⁴ to be prepared, and no phosphonic acid end groups are observed in these polymers. Thermal analyses of the poly(1,12-dodecamethylene phosphonate) have shown that this polymer has reasonable thermal stability (onset of thermal decomposition at 273 °C). This polymer also undergoes a cold crystallization process at 15 °C similar to that which has been observed in some polyesters, polyamides and elastomers.     

First mechanosynthesis of piperlotines A,C, and derivatives through solvent-free Horner–Wadsworth–Emmons reaction

Piperlotines are natural products characterized by an α,β-unsaturated amide moiety. These compounds found wide applications in Medicinal Chemistry like antibacterials, cytotoxic agents, anticoagulants, among others. To date, diverse methods of synthesis have been reported for piperlotines, but involving the use of catalysts, hazard reagents, anhydrous media or coupling reagents. Thus, in this work, we developed a greener method of synthesis of piperlotines A, C, and derivatives, through mechanochemical activation under solvent-free conditions. The reaction of a β-amidophosphonate, K₂CO₃, and an aromatic aldehyde afforded target compounds in moderate to good yields (46–77%), in an open atmosphere by grinding. It is worth to mention that this mechanochemical process was under thermodynamic control because just E isomer was isolated for every reaction. Moreover, synthesized piperlotines have been predicted by means of chemoinformatic analysis as potential therapeutic agents for the treatment of arthritis or cancer.