Mild and efficient Cs2CO3-promoted synthesis of phosphonates

A mild and convenient synthesis for phosphonates using cesium carbonate (Cs₂CO₃), tetrabutylammonium iodide (TBAI) and DMF was developed at room temperature. Numerous dialkyl phosphites were screened using a diverse array of alkyl halides and these reaction conditions were found to be highly efficient producing various phosphonates exclusively in moderate to high yields.     

A mild and highly efficient protocol for the one-pot synthesis of primary α-amino phosphonates under solvent-free conditions

Under solvent-free reaction conditions and in the presence of solid LiClO₄ a novel and mild protocol for the one-pot, three-component synthesis of primary α-amino phosphonates from an aldehyde, hexamethyldisilazane and a trialkyl phosphite is described giving high yields and having short reaction times. The same products are obtained in very low yields, when the three-component reaction is carried out under microwave irradiation and in the absence of solid LiClO₄. Examples of some prepared 1-aryl-N,N′-bis(arylidene)methanediamines are also described.     

Expedient and High-Yield Synthesis of Alkylphos-Phonyl Bichlorides Under Mild,Neutral Conditions: Reaction of Bis(Trimethylsilyl)Alkyl Phosphonates with Oxalyl Chloride/Dimethylformamide

Structurally variant bis(trimethylsilyl)alkyl phosphonates were converted in high yields (80–88%, distilled) to the corresponding phosphonyl dichlor-ides upon reaction with (COCl)₂/DMF.     

Synthesis and utility of new amine/nucleobase addition products of allenylphosphonates

In the reaction of allenylphosphonates with amines/nucleobases, depending on the amine and the allenylphosphonate, either Z- or E-vinylphosphonate or allylphosphonate as a single isomer with a β-amino functionality was isolated. A simple route to phosphonates with a β-NH₂ group is developed by direct reaction with ammonia. In reactions with adenine, three different modes of reaction, with one of them involving an unusual cyclisation, are observed. The utility of (enamino)allyl phosphonate products thus obtained in the synthesis of (enamino)-1,3-butadienes via Horner-Wadsworth-Emmons (HWE) reaction is also demonstrated.     

Synthesis of 2-cyclopropyl-4-pyrones and 5-cyclopropyl-2-alkylene-3(2H)-furanones based on tandem cyclization-cyclopropanation strategy

In AgSbF₆/Rh₂(OAc)₄/DCE system, two-component diastereoselective reactions of 2-diazo-3,5-dioxo-6-ynoates (phosphonates and sulphones) and alkenes provided easy access to 2-cyclopropyl-γ-pyrones through 6-endo-dig cyclization-cyclopropanation. In AgOAc/Rh₂(OAc)₄/Et₃N/DCE system, two-component reaction of 2-diazo-3,5-dioxo-7-aryl-6-ynoates and alkenes afforded 2-cyclopropyl-2-alkylene-3(2H)-furanones through 5-exo-dig cyclization-cyclopropanation. The possible mechanism of reaction is discussed. A simple procedure and mild conditions are significant features of this strategy.     

Enhanced removal of phosphonates from aqueous solution using PMS/UV/hydrated zirconium oxide process

Traditional treatment processes cannot completely remove phosphonates in circulating cooling water by one-step method. Herein, we designed peroxymonosulfate/UV irradiation/hydrated zirconium oxide (PMS/UV/HZO) coupling process to enhance the phosphonates removal. In particular, nitrilotris-methylenephosphonic acid (NTMP) removal efficiency by PMS/UV/HZO process was much higher than that of PMS/UV process, UV/HZO process and other processes in comparison experiments. Specifically, almost 97.2% NTMP in water was degraded, and the total phosphorous (TP) reduced from 9.3 mg/L to 0.26 mg/L at pH 7 within 180 min. TP removal efficiency still reached above 90% after 5 cycles adsorption-desorption of HZO. Moreover, Clˉ, NO₃ˉ and SO₄²ˉ ions all had negligible effect on NTMP removal. During the process, NTMP was first destroyed to form phosphates and other intermediates by the reactive oxygen species (ROS), then phosphates were in situ immobilized via HZO adsorption. Sulfate radical (SO₄^??) has been confirmed to be the major ROS in the reaction system by quenching experiment and electron paramagnetic resonance (EPR) characterization. And the excellent selective adsorption capacity of HZO for phosphate produced was attributed to the strong inner-sphere coordination between H₂PO₄ˉ/HPO₄²ˉ and Zr-OH on the surface of HZO. These results suggest that PMS/UV/HZO process is a promising technique for enhanced phosphonates decontamination.     

Indium triflate-catalyzed coupling of indoles with acyl phosphonates: synthesis of bis(indolyl)methane phosphonates

The coupling reaction of N-methylindole with alkyl and aryl phosphonate is described. The reaction works in the presence of 10 mol % of indium triflate and furnished bis(indolyl)methane phosphonates in good yield and high selectivity.     

Synthesis of 2-amino-1,3-dihydroxypropylphosphonates from Garner aldehyde

In the presence of triethylamine or ionic fluoride catalysts, the addition of dimethyl or diethylphosphite to Garner aldehyde proceeded with good (1:9) diastereoselectivity leading to a separable mixture of (1S,2S)- and (1R,2S)-hydroxyphosphonates. Almost equal amounts (43:57) of the respective phosphonates were formed when titanium(IV) isopropoxide was applied as a catalyst. The e.e.s of the hydroxyphosphonates reached 93–97% in the reactions catalysed by Ti(OiPr)₄ and dropped to 80–91% when triethylamine was used to catalyse the reaction.     

Al(H_2PO_4)_3 as an Efficient and Reusable Catalyst for One-pot Three-component Synthesis of α-Amino Phosphonates under Solvent-free Conditions

Synthesis of α‐amino phosphonates is described under solvent‐free conditions at 100°C from reaction between aldehydes and amines in the presence of trialkyl phosphites using Al(H₂PO₄)₃ as an efficient and reusable heterogeneous catalyst. The advantages of this procedure are short reaction time, flexibility and having high to excellent yields.     

Iodocyclization of trifluoromethylallenic phosphonates: an efficient approach to trifluoromethylated oxaphospholenes

α-Trifluoromethylallenic phosphonates were prepared by the reaction of diethyl chlorophosphite (DECP) and 4,4,4-trifluorobut-2-yn-1-ols in the presence of Et₃N. The iodocyclization of these fluorine-containing allenic phosphonates was achieved with iodine under mild conditions to give the corresponding trifluoromethylated oxaphospholenes in moderate to good yields.     

Synthesis of Some Dialkyl Bromo-Substituted Benzyl Phosphonates

Arbuzov reaction of bromo-substituted benzyl bromides and trialkyl phosphites in benzene gave high yields of dialkyl bromo-substituted benzyl phosphonates, and —CH₂CH₂CH₂CH₃). The structural assignments of these phosphonates were confirmed by ¹H nmr, ¹³C nmr, ir and mass spectral analysis.     

Synthesis of α-CF3-substituted γ,δ-didehydro lysine derivatives

An efficient and selective access to novel α-CF₃-substituted γ,δ-didehydro lysine derivatives and their phosphorus analogues has been developed via the Cu-catalyzed Mannich reaction of α-amino α-propargyl α-trifluoromethyl carboxylates or phosphonates with different secondary amines and paraformaldehyde.     

Synthesis of 3-(furyl)acrylates containing several phosphonate groups

Isomeric (diethoxyphosphorylmethyl)furoyl phosphonates react with ethoxycarbonylmethylenetriphenylphosphorane to form 3-[(diethoxyphosphorylmethyl)fyryl]-3-(diethoxyphosphoryl)acrylates with trans-location of phosphonate and ester groups regardless of the structure of heterocyclic residue. 2,5-Bis(diethoxyphosphorylmethyl)-3-furoyl phosphonate and 4,5-bis(diethoxyphosphorylmethyl)-2-furoyl phosphonate prepared from the corresponding acid chlorides via the Arbuzov reaction behave analogously. The dependence of coupling costants J _PP and J _PC on the location of phosphorus-containing substituents in the furan ring of these compounds is analyzed.     

Palladium-catalysed aminocarbonylation of iodoarenes and iodoalkenes with aminophosphonate as N-nucleophile

The high-yielding synthesis of novel N-acyl phosphonates with unprecedented structure was carried out by a homogeneous carbonylation reaction under mild reaction conditions. The palladium-catalysed aminocarbonylation of iodoalkenes (1-iodo-cyclohexene, 1-iodo-4-tert-butyl-cyclohexene, 1-iodo-2-methyl-cyclohexene and α-iodostyrene) with diethyl α-aminobenzyl-phosphonate as N-nucleophile resulted in the exclusive formation of carboxamides. The same reaction with iodoaromatics (iodobenzene, 2-iodothiophene) provided the corresponding carboxamide in high yields and some 2-keto-carboxamides as side products due to single and double carbon monoxide insertion, respectively.     

Direct oxidative phosphonylation of amines under metal-free conditions

Direct oxidation coupling of tertiary amines and dialkyl- or diphenyl-substituted phosphonates was developed. The reaction was mediated by DDQ under room temperature. Various phosphonates and N-aryl tetrahydroisoquinolines were tolerated in this reaction, and α-aminophosphonates were obtained with up to 99% yield.     

Lanthanide‐Catalyzed Selective Addition of Diethyl Phosphite to Chalcones

Lanthanide‐catalyzed addition of diethyl phosphite with chalcones was achieved under mild conditions. The reaction exhibited good product selectivity using different catalysts. γ‐Oxophosphonates were obtained in high yields in the reactions catalyzed by Yb(OAr)₃(THF)₂, while those catalyzed by [(Me₃Si)₂N]₃La(μ‐Cl)Li(THF)₃ afforded 1,2‐oxaphospholane‐5‐phosphonates as the main products in moderate to good yields. This methodology provides facile and practical approaches to the corresponding organophosphorus compounds with biological interest.     

An efficient and recyclable silica‐supported carbene–Cu(II) catalyst for the oxidative coupling reaction of terminal alkynes with H‐phosphonates under base‐free reaction conditions

The oxidative coupling reactions of terminal alkynes with H‐phosphonates were explored using SiO₂−NHC−Cu(II) (5.0 mol%) as catalyst at room temperature under base‐free reaction conditions. The reactions of a variety of terminal alkynes with H‐phosphonates generated the corresponding alkynylphosphonate products in good to excellent yields. In addition, SiO₂−NHC−Cu(II) could be recovered and recycled for six consecutive trials without significant loss of its reactivity. Copyright © 2011 John Wiley & Sons, Ltd.     

Synthesis of phosphorylated isoindolinone derivatives

The synthesis of diethyl [2-(2-alkyl-3-oxo-2,3-dihydro-1H-isoindol-1-yl)ethyl]phosphonates and diethyl [3-(2-alkyl-3-oxo-2,3-dihydro-1H-isoindol-1-yl)propyl]phosphonates, via metallation (sec-BuLi) of N-substituted isoindolin-1-ones and then the reaction of the generated lithiated species 4 with diethyl vinylphosphonate or diethyl 3-bromopropylphosphonate, respectively, is described.     

Synthesis of N-(alkoxycarbonyl or alkoxycarbonyl-methyl-alkoxyphosphonyl)-α-amino-O, O-diphenyl phosphonates and their bioactivities

With phosphonoformic acid (PFA) and its analog, phosphonoacetic acid (PAA), as the lead compounds, α-amino phosphonates were introduced into PFA and PAA. The derivatives of N-(alkoxycarbonyl-alkoxyphosphonyl)-α-amino phosphonates (I) and N-(alkoxycarbonyl-methyl-alkoxyphosphonyl)-α-amino phosphonates (II) with the N-terminal of amino phosphonates bonding to phosphorus atom of PFA andPAA were synthesized via the reaction of the corresponding phosphonyl chloride with α-amino phosphonates in the presence of a base. The³¹P NMR spectra of I and II were determined. It is found that the coupling constants³ J _pp with R³ being alkyl group were lower than those with R³ being (substituted) phenyl, and this result was discussed. The preliminary bioassay showed that some of the compounds I and II have better activities against tobacco mosaic virus (TMV). The inhibitory was higher than that of DHT (2, 4-dioxyhexahydro-1, 3, 5-triazine). In addition, some of the compounds showed the activity against cancer cells. Project supported by the National Natural Science Foundation of China.     

Stereochemistry of the addition of dialkyl phosphites to (S)-N,N-dibenzylphenylglycinal

The addition of various dialkyl phosphite derivatives to (S)-N,N-dibenzylphenylglycinal 6 led to the preponderance of anti over syn diastereoisomers: from 75:25 when NEt₃ or Ti(OiPr)₄ were used to 51:49 for Li or Mg salts. In the NEt₃-catalysed reaction, partially racemised phosphonates were formed, while enantiomeric products were obtained after addition of lithium O,O-dimethylphosphonate to (S)-6 at −70°C. Because the syn-isomers were found to be resistant to O-benzoylation, mixtures of diastereoisomers were easily separated after esterification of the anti products. Hydrogenation of the syn-phosphonates in the presence of Boc₂O gave enantiomeric dialkyl N-Boc-2-amino-1-hydroxy-2-phenylethylphosphonates—phosphonate analogues of the docetaxel C-13 side chain.