Stable Phosphoranes Research Articles

Tandem Wittig – Reductive annulation decarboxylation approach for the synthesis of indole and 2-substituted indoles

A simple tandem Wittig reaction-reductive decarboxylation route is established for the synthesis of indoles from commercially available o-nitrobenzaldehydes and a stable phosphorane. The method allows access to indoles in a very fast manner without involving any metal or expensive reagents or inert atmosphere. Also 2-substituted indoles are obtained which forms an important core of many biological active compounds.

A Simple Synthesis of Stable Phosphoranes Derived from Imidazole Derivatives.

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A Simple Synthesis of Stable Phosphoranes Derived from Imidazole Derivatives

Stable crystalline phosphorus ylides were obtained in excellent yields from the 1:1:1 addition reaction between triphenylphosphine and dialkyl acetylenedicarboxylates, in the presence of strong NH-acids, such as imidazole, 2-methylimidazole, 4-methylimidazole, 2-ethylimidazole, benzimidazole, and 5,6-dimethylbezimidazole. These stable ylides exist in solution as a mixture of two geometrical isomers as a result of restricted rotation around the carbon–carbon partial double bond resulting from the conjugation of the ylide moiety with the adjacent carbonyl group.

An efficient synthesis of stable sulfur-containing phosphoranes derived from 2-mercapto-1-methylimidazole and 2-thiazoline-2-thiol

Stable crystalline phosphorus ylides were obtained in excellent yields from the 1:1:1 addition reaction between triphenylphosphine and dialkyl acetylenedicarboxylates in the presence of strong SH-acids, such as 2-mercapto-1-methylimidazole and 2-thiazoline-2-thiol. These stable ylides exist in solution as a mixture of two geometrical isomers as a result of restricted rotation around the carbon–carbon partial double bond resulting from conjugation of the ylide moiety with the adjacent carbonyl group.

High-energy intermediate or stable transition state analogue: theoretical perspective of the active site and mechanism of beta-phosphoglucomutase.

A recent crystal structure of beta-phosphoglucomutase from Lactococcus lactis is reported to contain a five-coordinate phosphorus with five oxygen ligands that is a high-energy reaction intermediate during the phosphoryl transfer in the isomerization of beta-glucose 1-phosphate to beta-glucose 6-phosphate. Subsequently, it has been suggested that this structure is a transition state analogue with a five-coordinate magnesium with two oxygen and three fluorine ligands. Two layer ONIOM(B3LYP:PM3MM) calculations have been performed to address the nature of this intermediate and the mechanism of the phosphoryl transfer. These calculations provide evidence that (1) the observed crystal structure is consistent with a five-coordinate magnesium (a stable transition state analogue), not a five-coordinate phosphorus (a phosphorane) as a high-energy intermediate, (2) the active site is stabilized by the extensive hydrogen-bonding network, (3) the transfer of the phosphoryl group proceeds through a moderate barrier (14 kcal mol-1) five-coordinate phosphorus without a stable phosphorane or metaphosphate intermediate, (4) this concerted transition state is directly coupled to a proton transfer from the oxygen of glucose to the carboxylic group of aspartate 10, and (5) a stable glucose 1,6-bis-phosphoglucose intermediate is formed.

An Efficient Synthesis of Stable Sulfur-Containing Phosphoranes Derived from 1-Methylimidazole-2-thiol

Stable crystalline phosphorus ylides are obtained in excellent yields from the 1:1:1 addition reaction between triphenylphosphine and dialkyl acetylenedicarboxylates in the presence of 1-methylimidazole-2-thiol. These sulfur-containing phosphoranes exist in solution as a mixture of two geometrical isomers as a result of restricted rotation around the carbon-carbon double bond resulting from conjugation of the ylide moiety with the adjacent carbonyl group. Using dibenzoylacetylene as Michael acceptor, yields 2-[1-methyl-1 H -imidazole-2-yl)sulfanyl]-1,4-diphenyl-butane-1,4-dione.

A Simple Synthesis of Stable Phosphoranes Derived from Imides or Acetanilide Derivatives

Stable crystalline phosphorus ylides are obtained in excellent yields from the 1:1:1 addition reaction between triphenylphosphine, dialkyl acetylenedicarboxylates, and strong NH-acids, such as acetanilide, 4-methylacetanilide, 2-cyanoacetanilide, 4-bromoacetanilide, 4-methoxyacetanilide, succinimide, malimide, or phthalimide. These stabilized phosphoranes exist as a mixture of two geometrical isomers as a result of restricted rotation around the carbon-carbon partial double bond resulting from conjugation of the ylide moiety with the adjacent carbonyl group.

First Representatives of Stable Phosphoranes Derived from Bicyclophosphorylated Carbohydrates

1,2-O-Isopropylidene-α-D-glucofuranose 3,5,6-phosphite was stidied in reactions with α-dicarbonyl compounds. Reagents with the electron-acceptor halogen atom form with the former stable phosphoranes, while unsubstituted α-dicarbonyl compounds, the corresponding normal phosphates.

P(IV)-P(V) Coordinational Isomerism of Phosphorus N-α-Haloethylimines

The semiempirical MNDO-PM3 method in supramolecular approximation was used to study the structure of (N-α-haloethylimino)chloro(o-phenylenedioxy)phosphoranes R1 3CR2X-N-P(Cl)O2C6H2(R3-m)2, where R1 = H, Cl, F, R2 = R3 = H, Cl, and X = F, Cl, Br, and of their 1:2 solvates with chloroform, as well as alternative mechanisms of the P(IV)-P(V) holotropic rearrangement. It was found that the activation barrier of the sigmatropic rearrangement increases in the order Br < Cl < F, in parallel with increasing thermodynamic stability of a more stable phosphorane isomer with an axial-equatorial arrangement of the dioxaphos- phole ring. It was shown that the most favorable pathway of the phosphorus-carbon halotropic rearrangement of a phosphorus N-α-haloethylimine, both nonsolvated and solvated with two molecules of chloroform, is the sigmatropic transformation.

Synthesis of Pentacoordinate Phosphorus Haptens for Catalytic Antibody Production. Bait and Switch Concept

Abstract: Our objective is to obtain monoclonal antibodies which will catalyse the hydrolysis of phosphorus-based nerve agents. Our syntheses followed three strategies. The first was synthesis of stable pentacoordinate phosphoranes as haptens for the production of monoclonal catalytic antibodies based on the transition state for phosphonate hydrolysis. The second approach is based upon the potential addition of water to the phosphorus atom of a tetracoordinate fluorine containing phosphate to yield an intermediary pentacoordinate system. In the third approach the “bait and switch” concept was used.

Reactions of 5-arylimino-4-chloro-5 H-1,2,3-dithiazoles with stable phosphoranes: Novel preparation of dithiomethylenephosphoranes

The reactions of 5-arylimino-4-chloro-5H-1,2,3-dithiazoles with 2 equivalents of stable phosphoranes such as carboethoxymethylene-, acetylmethylene-, 4-chlorobenzoylmethylene-, and cyanomethylenetriphenylphosphoranes in the presence of pyridine in CH 2Cl 2 at room temperature gave a new type of the corresponding phosphoranes with aryliminocyanomethyldithiomethylene moiety as a major product.

Application of the aza-Claisen rearrangement to the total synthesis of natural products: (-)-Isoiridomyrmecin

Abstract

Phosphate ester hydrolysis: calculation of gas-phase reaction paths and solvation effects

Quantum-mechanical and solvation-effect calculations of the hydrolysis mechanism of dimethyl and ethylene phosphate, which are model compounds for the hydrolysis of DNA and RNA, respectively, are reported and used to explain the fact that in solution, five-membered-ring cyclic phosphates hydrolyse 106–108 times faster than acyclic esters. Ab initio energy profiles for the base-catalysed hydrolysis (i.e. attack by OH–) of dimethyl and ethylene phosphate are determined at the Hartree–Fock level and with MP2 correlation corrections. The reaction proceeds through the formation of a pentacovalent phosphorane transition state with attack by the hydroxide ion as the rate-determining step; stable phosphorane intermediates are not observed in the gas phase. A detailed analysis is made of the ring strain in the cyclic phosphate reactant, which had been proposed as the origin of the observed rate effect and the results for the reactants are compared with those for the transition state. Although there is strain in the ground state of the cyclic reactant, it does not contribute to the rate acceleration because of dihedral angle constraints present in the cyclic transition state. An estimate of solvation effects indicates that most of the rate acceleration observed in solution arises from differential solvation of the transition states.

Design, synthesis and anti-enzymatic activity of novel water-stable fluorine-containing phosphoranes

The first approach to antibodies with enzymatic activity in pyrophosphates is to find water-stable haptens which could show potential as substrates or inhibitors against phosphorolytic enzymes. In the simple case (competitive agents) this requires design of stable phosphoranes with a trigonal-bipyramidal structure such as in some fluorine-substituted phosphoranes. We established that the interatomic distances pattern in bipyramid residues is more suitable for the molecules II and III when the MMX calculations (PCMODEL program, N. Allinger) of Mg ++ — diphosphate (MgPP; I-transition state for the inorganic yeast pyrophosphatase substrate) and some model synthetic compounds were made. Correlation coefficients between interatomic distances in bipyramids for I–II and I–III pairs are 0.991 and 0.921 respectively. ▪ Compounds II and III were synthesized by our method. Anti-enzymatic activity was studied with MgPP as substrate. Compound II was more active than III, as expected, and both showed activities as syncatalithic inhibitors. Constant of the pseudo-irreversible inhibition for II is 1.2×10 7 M −1 min −1.

CHEMISTRY OF PHOSPHORUS YLIDES 101REACTION WITH PHOSPHACUMULENES IV. SYNTHESIS OF PYRAN, PHOSPHORANYLIDENE, OXAPHOSPHORIN AND OXAZAPHOSPHORIN FROM THE REACTION OF 1,3-DIOXO-Δ2,α-INDANMALONONITRILE WITH PHOSPHORANES AND IMINOPHOSPHORANES

Abstract 1,3-Dioxo-Δ2,α-indanmalononitrile (1) reacts with the active ketenylidene-(2a) and thioketenylidenetriphenyl phosphorane (2b) to give the corresponding pyrans 3 (X[dbnd]O or S). The reaction of pyran 3 with p-nitrobenzaldehyde proceeds according to the Wittig reaction to give the respective ethylenes 4a, b. On the other hand, phosphoranylidenes 7a-e were isolated from the reaction of stable phosphoranes 5a-e with the dioxoindanmalononitrile 1. Moreover, the oxaphosphorin 9 and oxazaphosphorin 11, were prepared from the reaction of compound 1, with the phosphorane 8, and the iminophosphorane 10, respectively. Structures of the new compounds were assigned according to consistent analytical and spectroscopic measurements.

Transition-state structures for enzymatic and alkaline phosphotriester hydrolysis.

The primary and secondary 18O isotope effects for the alkaline (KOH) and enzymatic (phosphotriesterase) hydrolysis of two phosphotriesters, O,O-diethyl p-nitrophenyl phosphate (I) and O,O-diethyl O-(4-carbamoylphenyl) phosphate (II), are consistent with an associative mechanism with significant changes in bond order to both the phosphoryl and phenolic leaving group oxygens in the transition state. The synthesis of [15N, phosphoryl-18O]-, [15N, phenolic-18O]-, and [15N]-O,O-diethyl p-nitrophenyl phosphate and O,O-diethyl O-(4-carbamoylphenyl)phosphate is described. The primary and secondary 18O isotope effects for the alkaline hydrolysis of compound I are 1.0060 and 1.0063 +/- 0.0001, whereas for compound II they are 1.027 +/- 0.002 and 1.025 +/- 0.002, respectively. These isotope effects are consistent with the rate-limiting addition of hydroxide and provide evidence for a SN2-like transition state with the absence of a stable phosphorane intermediate. For the enzymatic hydrolysis of compound I, the primary and secondary 18O isotope effects are very small, 1.0020 and 1.0021 +/- 0.0004, respectively, and indicate that the chemical step in the enzymatic mechanism is not rate-limiting. The 18O isotope effects for the enzymatic hydrolysis of compound II are 1.036 +/- 0.001 and 1.0181 +/- 0.0007, respectively, and are comparable in magnitude to the isotope effects for alkaline hydrolysis, suggesting that the chemical step is rate-limiting. The relative magnitude of the primary 18O isotope effects for the alkaline and enzymatic hydrolysis of compound II reflect a transition state that is more progressed for the enzymatic reaction.

Trimethylsilylphosphite und Hexafluoraceton: Phosphonate versus Dioxaphospholane — 1:1- und/oder 1:2-Addukte / Trimethylsilylphosphites and Hexafluoroacetone: Phosphonates versus Dioxaphospholanes —1:1 and/or 1:2 Adducts

The [2,2,2-trifluoro-1-(trifluoromethyl)-1-(trimethylsiloxy)ethyl]phosphonates 2a-g and/or the 4,4,5,5-tetrakis(trifluoromethyl)-1,3,2λ5σ4-dioxaphospholanes 4a-c, e were obtained from the silylphosphites 1a-g and hexafluoroacetone depending on the reaction conditions. Intermediates were the λ5σ5-phosphoranes 3a-e formed by an 1:2 oxidative addition of hexafluoroacetone whereas in the case of the cyclic phosphites 1f and g thermally stable phosphoranes, 3f, 6 and 3g were found to undergo no substituent exchange

A PHOSPHORANE WITH A (λ5)-PHOSPHORUS-SILICON BOND

Abstract Reaction of bis(trimethylsilyl)magnesium with bis(catechyl)chlorophosphorane has furnished the first phosphorane with a (λ5)-phosphorus-silicon bond, extending the range of atoms known to give rise to stable phosphoranes when bonded to five-co-ordinate phosphorus. The novel phosphorane has been characterized by analysis, n.m.r. spectra and from its mass spectrum.

Perkov reaction in series of mixed bis(1,1,3-trihydroperfluoropropyl) alkyl phosphites

Mixed bis(1,1,3-trihydroperfluoropropyl) alkyl phosphites react under mild conditions with chloral to simultaneously give stable phosphoranes with a P-C bond and vinyl phosphates.

PENTACOORDINATE SPIROCYCLIC DERIVATIVES OF THE 2H-1,2,3-DIAZAPHOSPHOLE SYSTEM

Abstract Stable spirocyclic phosphoranes 2 have been prepared stereospecifically in high yields (90–95%) by reaction of o-azidophenol with cis and trans-diazaphosphole derivatives 1. Slow isomerization of pure diastereoisomer 2 was observed in acidic conditions.