Addition of Organometallic Reagents to Chiral N‐Methoxylactams: Enantioselective Syntheses of Pyrrolidines and Piperidines

Enantioselective iridium‐catalyzed allylic substitutions were used to prepare N‐allyl hydroxamic acid derivatives that were suitable for ring‐closing metathesis, giving N‐methoxylactams. Reactions of these derivatives with Grignard or organolithium compounds gave hemiaminals, which could be reduced diastereoselectively via acyliminium intermediates to give cis‐piperidines or cis‐pyrrolidines with substituents in the 2,6‐ or 2,5‐positions, respectively. In addition, compounds with a quaternary carbon center could be synthesized by corresponding reactions with potassium cyanide/AcOH. The procedures were applied in the syntheses of alkaloids (?)‐209D and (+)‐prosophylline.     

Base-Catalyzed Polymerization of Vinyl Acetamide and Allyl Cyanide

The base-catalyzed polymerizations of vinyl acetamide and allyl cyanide have been studied. It was found by chemical and spectroscopic analyses that the polymer obtained from vinyl acetamide was poly(2-methyl-β-alanine), which was the same structure as the polymer prepared by base-catalyzed polymerization of crotonamide. It is concluded, therefore, that vinyl acetamide was polymerized through the isomerization of allyl group and the proton transfer reaction from amide group. The gas-chromatographic analysis of the polymerization system showed that vinyl acetamide was consumed faster than crotonamide. This, fact suggests that an intermediate other than crotonamide might be present in the process of isomerization of vinyl acetamide. On the other hand, in the base-catalyzed polymerization of allyl cyanide, the allyl group was isomerized, but the reaction of cyanide group hardly occurred.     

Highly active, regioselective, and enantioselective hydroformylation with Rh catalysts ligated by Bis-3,4-diazaphospholanes

Azines made by the reaction of hydrazine with ortho-formylbenzoic acid react with 1,2-diphosphinobenzene and either succinyl chloride or phthaloyl chloride in ca. 30% yield to give rac-bis-3,4-diazaphospholanes bearing benzoic acid groups in the 2 and 5 positions. Condensation of the benzoic acid functionalities with enantiomerically pure amines affords diastereomeric benzoamides which can be separated by flash chromatography. Application of the resolved bis-3,4-diazaphosholanes to Rh-catalyzed enantioselective hydroformylation of styrene, allyl cyanide, and vinyl acetate under mild pressures (20-500 psig of CO/H2) and temperatures (40-120 degrees C) reveals high activities and selectivities for all three substrates. At 60 degrees C and 500 psig syn gas, the best ligand provides outstanding regio- and enantioselectivities (styrene, 89% ee, b:l = 30:1; allyl cyanide, 87% ee, b:l = 4.8:1; vinyl acetate, 95% ee, b:l = 40:1) while achieving turnover frequencies of ca. 3000 h-1.     

Photoaccelerated synthesis of 2-vinylpyridines from unsaturated nitriles and ethyne

The heterocyclization of unsaturated nitriles and ethyne catalyzed by cyclopentadienyl-1,5-cis,cis-cyclooctadiene-cobalt(I) and promoted by light has been studied in toluene as solvent. Acrylonitrile and substituted acrylonitriles gave results of interest in the preparation of 2-vinylpyridines. No reaction could be observed using fumaronitrile, maleonitrile or allyl cyanide. The (E)/(Z)-ratio of educts and products seems to be not influenced by conditions in the reaction.     

An Unexpected Reaction of Allylic Propynoate under Palladium(II) Catalysis

ＩｎｔｒｏｄｕｃｔｉｏｎＩｎｔｈｅｐａｓｔｓｅｖｅｒａｌｙｅａｒｓ ,ｐａｌｌａｄｉｕｍ ｃａｔａｌｙｚｅｄｅｎｙｎｅｃｏｕｐｌｉｎｇｒｅａｃｔｉｏｎｓｈａｖｅｂｅｅｎｅｘｐｌｏｒｅｄａｓｔｏｏｌｓｆｏｒｔｈｅｓｙｎ ｔｈｅｓｉｓｏｆｌａｃｔｏｎｅｓｆｒｏｍａｃｙｃｌｉｃａｌｌｙｌｉｃａｌｋｙｎｏａｔｅｓ .1α Ａｌｋｙｌｉｄｅｎｅ γ ｂｕｔｙｒｏｌａｃｔｏｎｅｓｔｒｕｃｔｕｒｅｕｎｉｔｃｏｕｌｄｂｅｅａｓｉｌｙａｓｓｅｍｂｌｅｄｔｈｒｏｕｇｈｈａｌｏｐａｌｌａｄａｔｉｏｎ ,2 ｉｎｔｒａｍｏｌｅｃｕｌ…     

Competing Reaction Pathways in Heterogeneously Catalyzed Hydrogenation of Allyl Cyanide: The Chemical Nature of Surface Species

We present a mechanistic study on the formation of an active ligand layer over Pd(111), turning the catalytic surface highly active and selective in partial hydrogenation of an α,β-unsaturated aldehyde acrolein. Specifically, we investigate the chemical composition of a ligand layer consisting of allyl cyanide deposited on Pd(111) and its dynamic changes under the hydrogenation conditions. On pristine surface, allyl cyanide largely retains its chemical structure and forms a layer of molecular species with the CN bond oriented nearly parallel to the underlying metal. In the presence of hydrogen, the chemical composition of allyl cyanide strongly changes. At 100 K, allyl cyanide transforms to unsaturated imine species, containing the C=C and C=N double bonds. At increasing temperatures, these species undergo two competing reaction pathways. First, the C=C bond become hydrogenated and the stable N-butylimine species are produced. In the competing pathway, the unsaturated imine reacts with hydrogen to fully hydrogenate the imine group and produce butylamine. The latter species are unstable under the hydrogenation reaction conditions and desorb from the surface, while the N-butylimine adsorbates formed in the first reaction pathway remain adsorbed and act as an active ligand layer in selective hydrogenation of acrolein.     

Photodissociation/gas-diffusion separation and fluorimetric detection for the analysis of total and labile cyanide in a flow system

Total cyanide species are determined in a flow injection system which includes UV-photodissociation, gas-diffusion separation and spectrofluorimetric detection. Without the irradiation step, only cyanide easily released in acid medium, i.e. labile cyanide, is determined. Cyanide diffuses through a microporous PTFE membrane from an acid donor stream to a sodium hydroxide acceptor stream. Then, the transferred cyanide reacts with ?o-phthalaldehyde and glycine to form a highly fluorescent isoindole derivative. Complete cyanide recoveries were obtained for the most important metal cyanide complexes found in environmental samples, excepting cobaltocyanide. The sampling frequency for total cyanide was 4 samples h^–1 and the detection limit was 0.4 μg L^–1. Recoveries of total cyanide from river water obtained with this method are about 90% of those obtained with APHA Method 4500-CN C for total cyanide. Received: 10 February 1999 / Revised: 7 May 1999 / Accepted: 13 May 1999     

Cyclocopolymerization of allyl‐acrylate quaternary ammonium salts with diallyldimethylammonium chloride

A series of copolymers of N,N‐dialkyl‐N‐2‐(methoxycarbonyl)allyl allyl ammonium chloride, N,N‐dialkyl‐N‐2‐(ethoxycarbonyl)allyl allyl ammonium chloride, and N,N‐dialkyl‐N‐2‐(t‐butoxycarbonyl)allyl allyl ammonium bromide with diallyldimethylammonium chloride (DADMAC) were prepared in water at 60 °C with 2,2′‐azo‐bis(2‐amidinopropane)dihydrochloride. A strong effect of ester substituents on cyclopolymerization was observed. The methyl and ethyl ester monomers showed high cyclization efficiencies during homopolymerizations and copolymerizations. Unexpectedly, the t‐butyl ester derivatives showed high crosslinking tendencies. Water‐soluble copolymers were obtained only with a decrease in the molar fraction of t‐butyl ester monomer below 30%. Relative reactivities of the allyl‐acrylate monomers in photopolymerizations were compared with the relative reactivity of DADMAC. Allyl‐acrylate monomers were much more reactive than DADMAC; the photopolymerization rate decreased in the following order: N,N‐morpholine‐N‐2‐(t‐butoxycarbonyl)allyl allyl ammonium bromide > N,N‐piperidyl‐N‐2‐(t‐butoxycarbonyl)allyl allyl ammonium bromide > N,N‐dibutyl‐N‐2‐(ethoxycarbonyl)allyl allyl ammonium chloride > N,N‐piperidyl‐N‐2‐(ethoxycarbonyl)allyl allyl ammonium chloride ∼ N,N‐morpholine‐N‐2‐(ethoxycarbonyl)allyl allyl ammonium chloride ∼ N,N‐piperidyl‐N‐2‐(methoxycarbonyl)allyl allyl ammonium chloride > N‐methyl‐N‐butyl‐N‐2‐(ethoxycarbonyl)allyl allyl ammonium chloride. Intrinsic viscosities of the polymers measured in 0.09 M NaCl ranged from 1.06 to 3.20 dL/g. The highest viscosities were obtained for copolymers of the t‐butyl ester monomers with piperidine and morpholine substituents. The copolymer of the t‐butyl ester with piperidine substituent and DADMAC was hydrolyzed in acid to give a polymer with zwitterionic character. © 2001 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 39: 640–649, 2001     

A study of the structures of decomposing and non-decomposing [C4H5N]+˙ ions formed from different neutral species

[C₄H₅N]^+˙ ions have been generated from eleven neutral species. From a study of their metastable transitions and the translational energy released in the fragmentation in which C₂H₂ is lost, it is concluded that [C₄H₅N]^+˙ ions with sufficient energy to decompose do so from a common structure or mixture of structures when they are generated from crotonitrile, allyl cyanide, cyclopropyl cyanide, methacrylontrile, pyrrole, 2-, 3- and 4-hydroxypyridines and 2-aminopyridine. The [C₄H₅N]^+˙ ions formed from allyl isocyanide decompose from a different structure and those given by cyclopropyl isocyanide appear to decompose from a mixture of the two structures. Non-decomposing [C₄H₅N]^+˙ ions were investigated by means of their collision induced decomposition spectra using a B/E linked scan. Six different structures or mixtures of structures are suggested to explain these observations.     

Synthesis and application of a new bisphosphite ligand collection for asymmetric hydroformylation of allyl cyanide

A series of mono- and bidentate phosphites was prepared with (S)-5,5',6,6'-tetramethyl-3,3'-di-tert-butyl-1,1'-biphenyl-2,2'-dioxy [(S)-BIPHEN] as a chiral auxiliary and screened in the asymmetric hydroformylation of allyl cyanide. These hydroformylation results were compared with those of two existing chiral ligands, Chiraphite and BINAPHOS, whose utility in asymmetric hydroformylation has been previously demonstrated. Bisphosphite 11 with a 2,2'-biphenol bridge was found to be the best overall ligand for asymmetric hydroformylation of allyl cyanide with up to 80% ee and regioselectivities (branch-to-linear ratio, b/l) of 20 with turnover frequency of 625 [h(-)(1)] at 35 degrees C. BINAPHOS gave enantioselectivities up to 77% ee when the reaction was conducted in either acetone or neat but with poor regioselectivity (b/l 2.8) and activities 7 times lower than that of 11. The product of allyl cyanide hydroformylation using (R,R)-11 was subsequently transformed into (R)-2-methyl-4-aminobutanol, a useful chiral building block. Single-crystal X-ray structures of (S,S)-11 and its rhodium complex 19 were determined.     

Thiol‐ene clickable hyperscaffolds bearing peripheral allyl groups

Radical catalyzed thiol‐ene reaction has become a useful alternative to the Huisgen‐type click reaction as it helps to expand the variability in reaction conditions as well as the range of clickable entities. Thus, direct generation of hyperbranched polymers bearing peripheral allyl groups that could be clicked using a variety of functional thiols would be of immense value. A specifically designed AB₂ type monomer, that carries two allyl benzyl ethers groups and one alcohol functionality, was shown to undergo self‐condensation under acid‐catalyzed melt‐transetherification to yield a hyperbranched polyether that carries numerous allyl end‐groups. Importantly, it was shown that the kinetics of polymerization is not dramatically affected by the change of the ether unit from previously studied methyl benzyl ether to an allyl benzyl ether. The peripheral allyl groups were readily clicked quantitatively, using a variety of thiols, to generate an hydrocarbon‐soluble octadecyl‐derivative, amphiphilic systems using 2‐mercaptoethanol and chiral amino acid (N‐benzoyl cystine) derivatized hyperbranched structures; thus demonstrating the versatility of this novel class of clickable hyperscaffolds. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Trapping of fatty acid allyl radicals generated in lipoxygenase reactions in biological fluids by nitroxyl radical

Nitroxyl radicals can trap fatty acid allyl radicals on ferric‐lipoxygenases at lower oxygen content, which are an intermediate in the lipoxygenase reaction. In the present study, we examined whether nitroxyl radical‐trapping of fatty acid allyl radicals on the enzyme proceeds in biological fluids with abundant antioxidants. The fatty acid allyl radical–nitroxyl radical adducts were quantified by HPLC with electrochemical detection (HPLC‐ECD); the adducts in eluate degraded into nitroxyl radical by passing through heating coil at 100°C, and then nitroxyl radical was detected by electrochemical detector. Soybean 15‐lipoxygenase and nitroxyl radical (3‐carbamoyl‐2,2,5,5‐tetramethyl‐3‐pyrroline‐N‐oxyl, CmΔP) were mixed with rat serum prepared from fresh venous blood, and the solution was stood at 37°C for 1 h. One volume of the solution was mixed with 5 vols of cold acetonitrile. After centrifugation, the supernatant was subjected to HPLC‐ECD. Arachidonate allyl radical–CmΔP adducts as well as linoleate allyl radical–CmΔP adducts were detected in the solution, and the content of these adducts remarkably increased in the presence of phospholipase A₂. It is proved for the first time that nitroxyl radical traps fatty acid allyl radicals generated in the lipoxygenase reaction in biological fluid without competition from endogenous antioxidants. Copyright © 2010 John Wiley & Sons, Ltd.     

Unprecedented stereoselective synthesis of 3-methylisoxazolidine-5-aryl-1,2,4-oxadiazoles via 1,3-dipolar cycloaddition and study of their in vitro antioxidant activity

The stereoselective 1,3-dipolar cycloaddition between allyl cyanide and a menthone-derived nitrone led to the desired isoxazolidine in good yield. Once the nitrile group transformed to an amidoxime group, the cyclocondensation of various aldehydes with chiral amidoxime led to unprecedented enantiopure 3-methylisoxazolidine-5-aryl-1,2,4-oxadiazoles. The menthone chiral auxiliary was then removed with acid hydrolysis. The new compounds were also screened for their in vitro antioxidant activity using DPPH and FRAP assays. Some of the compounds showed promising antioxidant activity.     

Notiz über einen Zugang zu β, γ-ungesättigten Carbonsäurederivaten mit Hilfe der Amidacetal-Claisenumlagerung. Über synthetische methoden, 17. Mitteilung

Note on a preparation of β, γ-unsaturated carboxylic acid derivatives using the amide acetal Claisen rearrangement 3-(Trimethylsilyl)allyl alcohols smoothly undergo the amide acetal Claisen rearrangement furnishing allyl silanes. Subsequent protolysis with HF at ?20° provides a convenient, stereoselective method for the preparation of β, γ-unsaturated carboxylic acid derivatives. Three model examples illustrate the procedure.     

PHOSPHORORGANISCHE VERBINDUNGEN 901

Abstract

Aus Allylamido-phosphoniumsalzen wird durch trockenes Tetrabutylammoniumcyanid in Methylenchlorid die Allylgruppe unter Erhaltung der Konfiguration und Bildung von Phosphinigsäureamiden abgespalten (P-C-Cyanolyse). Allyl-O-alkyl-phosphoniumsalze reagieren unter den oben genannten Bedingungen nach Arbusov, Allyl-S-alkyl-phosphoniumsalze aber unter Spaltung der P-S-Bindung ab. (P-S-Cyanolyse).

Das System: Tetrabutyl-ammoniumcyanid in Methylenchlorid kann ohne Nachteil für die Ausbeute durch KCN und katalytische Mengen 18-Krone-6 in Methylenchlorid ersetzt werden. Optisch aktives Benzyl-methyl-phenyl-phosphinsulfid kann auf diese Weise unter Erhaltung der Konfiguration desulfuriert werden.

Auch Dithiophosphinsäureester und Thiophosphinsäureamide werden nach vorausgehender S-Alkylierung (Überführung in die entsprechenden Quasiphosphoniumsalze) mit Tetrabutylammoniumcyanid unter Bildung von Thiophosphinigsäureestern bzw. Phosphinigsäureamiden desulfuriert. Thiophosphinsäure-O-alkylester R₂P(S)OR' liefern über diese Reaktionsfolge nach Arbusov Thiophosphinsäure-S-alkylester R₂P(O)SR′.

Die P-C-Cyanolyse von Allyltriphenyl-phosphoniumbromid mit KCN/18-Krone-6 oder Tetrabutyl-ammoniumcyanid bleibt im aprotischen Medium auf der rotgefärbten Ylidstufe stehen. Erst nach Zugabe eines Protonendonators läuft die Isomerisierung zum Propenyl-phosphoniumsalz ab.

Treatment of allylamido-phosphorlum salts with dry tetrabutylammonium cyanide in methylenechloride delivers after removal of the allyl group phosphinous acid amides with retention of configuration (P-C-cyanolysis).

Allyl-O-alkylphosphonium salts undergo the Arbusov reaction under the above conditions, while allyl-S-alkyl phosphonium salts undergo fission of the P[sbnd]S bond (P-S cyanolysis).

Equally good results were obtained using KCN in methylene chloride accompanied by catalytic amounts of 18-crown-6 ether; thus optically active benzyl-methyl-phenyl-phosphine-sulfid gave the corresponding phosphine with retention of configuration.

Dithiophosphinic acid esters and thiophosphinic acid amides, after conversion to the corresponding quasiphosphonium salts via S-alkylation and subsequent treatment with tetrabutylammonium cyanide in methylenechloride, also give the corresponding thiophosphinous acid ester and phosphinous acid amide respectively. Thiophosphinic acid O-alkyl esters (R₂P(S)OR′) give however the thiophosphinic S-alkyl ester (R₂P(O)SR′) via an Arbusov reaction.

The P-C cyanolysis of allyl-triphenylphosphoniumbromide using KCN/18-crown-6 or tetrabutylammonium cyanide in aprotic medium stops at the stage of the intermediary red-coloured ylide; addition of a proton-donor then results in the subsequent rearrangement to the corresponding propenyl-phosphonium salt.     

Metathesis of allyl cyanide in the presence of a catalytic system containing tungsten hexachloride and 1,1,3,3-tetramethyl-1,3-disilacyclobutane

Conclusions The metathesis of allyl cyanide was carried out by the action of a catalytic system containing tungsten hexachloride by 1,1,3,3-tetramethyl-1,3-disilacyclobutane.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 4, pp. 920–921, April, 1988.     

Syntheses and characterizations of allyl cellulose and glycidyl cellulose

Allyl cellulose was synthesized by reacting cellulose with allyl bromide in homogeneous LiCl/DMAc solution containing NaOH powder. The degree of substitution (DS) per anhydroglucose (AHG) unit was determined by titrating the allyl cellulose with bromine in chloroform solution, and an allyl DS of 2.80 was found. Glycidyl cellulose was then prepared by reacting this allyl cellulose with peracetic acid in methylene chloride at ambient temperature for 6 days. The measured reaction rate constant was 1.33 × 10^?3 min^?1. The glycidyl cellulose thus obtained with a glycidyl DS of 2.58 was determined by titrating the product with perchloric acid in conjunction with tetrabutylammonium iodide. The 2.58 of glycidyl DS was also confirmed by ¹H-NMR integration. Both allyl cellulose and glycidyl cellulose were analyzed and characterized with FTIR, ¹H-NMR, ¹³C-NMR, TGA, and GPC. During epoxidation of allyl cellulose, possible side reaction leading to ester formation was evidenced from the continuous increase of v_{C? O} at 1735 cm^?1 in FTIR analyses. In addition, a bimodal distribution and a decreased molecular weight for glycidyl cellulose were found from GPC data, which might suggest a possible chain scission at the cellulosic ether linkage. © 1992 John Wiley & Sons, Inc.     

Unexpected formation of pyrido[2,3-d]pyrimidine system from simple linear components

A system of pyrido[2,3-d]pyrimidine series was obtained in a one-pot synthesis from diethyl ethoxymethylidenemalonic acid, cyanothioacetamide, and allyl bromide.     

Kinetics of Chlorohydrination of Allyl Chloride

The chlorohydrination of allyl chloride with chlorine in water was studied at 20–80°C. The effect of the concentration of chloride ions within the range 0–3.6 mol/l on the selectivity of formation of glycerol dichlorohydrins was studied. An equation that relates the selectivity and the concentration of Cl^–was derived, which adequately describes experimental data. The schemes of parallel and consecutive reactions occurring in the system were suggested. The ratios between the rate constants of the following reactions were found: the reactions of chlorine with water and allyl chloride dissolved in water (k ₁/k ₄= 4.1 × 10^–4), the reaction of allyl chloride with hypochlorous acid and the decomposition of hypochlorous acid (k ₂/k ₃= 1.7 × 10³), and the reactions of the allyl chloride–chlorine complex with a water molecule and Cl^–(k ₅/k ₆= 2.9 × 10^–2).     

Preparation of a new hydrophilic copolymer from poly(α-hydroxyacrylic acid)

A new hydrophilic copolymer containing α-hydroxy allyl alcohol segments was prepared by reducing poly(α-hydroxyacrylic acid) (PHA) with NaBH₄ in water and mixed solvents of methanol and polar solvents. Conversion to the desired allyl alcohol group in the resultant polymers was confirmed with ICP, FT-IR, and ¹³C NMR spectroscopies. The degree of conversion was as low as 5% for PHA reduced in aqueous solution, while for those reduced in the mixed solvents it was significant (ca. 60–70%).