Studies on Ptc-Wittig Reaction of Diphenyl Ylids

Abstract

The phase transfer catalyzed (PTC) Wittig reaction has the advantage of not requiring additional catalyst due to the catalytic property of phosphonium salt itself. This report presents the studies on such a reaction of diphenyl-, di-alkyl- and methyl-2-butenyl phosphonium ylids which are produced in situ from the corresponding phosphonium salts.     

Scope and Limitation of the Reactions of 3-Imino Derivatives of Pentane-2,4-Diones with Organophosphorus Reagents

Abstract

3-(Hydroxyimino)pentane-2,4-dione reacts with phosphonium ylides, Wittig–Horner reagents, trialkyl phosphites, and Lawesson's reagents to give the olefinic and cyclic products, the phosphonate adducts, the dialkyl phosphate products, the phosphinodithioic acid, and 2,4-dithione products, respectively. Furthermore, the reaction of 3-(phenylimino)pentane-2,4-dione with Wittig, Wittig–Horner reagents and trialkyl phosphite resulted in the formation of 2,5-diendioate, diethoxy phosphoryl hexanoate and the phosphate products. Possible reaction mechanisms are considered and the structural assignments are based on analytical and spectroscopic results. The antibacterial and antifungal activities for some of the new compounds are also reported.     

Stereocontrol in Organic Synthesis Using the Diphenylphosphoryl Group

In 1959, Horner showed that metalated alkyldiphenylphosphane oxides react with aldehydes or ketones to give alkenes. With this reaction, the diphenylphosphoryl (Ph₂PO) group made its entrance into synthetic organic chemistry. In the thirty-six years since that date, extensive research has shown that this olefination, the Horner–Wittig reaction, has unique properties that make it much more than simply the phosphane oxide cousin of the more famous phosphorus-based olefinations—the Wittig reaction (based on phosphonium salts) and the Wadsworth–Emmons reaction (based on phosphonate esters). Early work on the Horner–Wittig reaction concentrated on the reactivity of phosphane oxides and the regioselectivity of their reactions, but more recently the power of the Ph₂PO group to control the stereochemistry of alkenes, and to produce “on demand” either stereoisomer in high stereochemical purity, has emerged. From the study of these stereocontrolled Horner–Wittig reactions arose the realization that the Ph₂PO group is useful not only for the control of the two-dimensional stereochemistry of alkenes, but also of three-dimensional stereochemistry in general. After a brief introduction to phosphane oxide chemistry, this review will examine the Horner–Wittig reaction, in both its original and “stereocontrolled” varieties. From there, we will move on to an account of the stereoselective construction of molecules containing the Ph₂PO group, concentrating on the stereochemical directing effects of the Ph₂PO group and on the role of its unique combination of attributes—steric bulk, electronegativity, and Lewis basicity—in controlling these reactions. Finally, we will present what is intended as a practical guide to this chemistry, covering the type of functionalized alkenes that have been made with the help of the Ph₂PO group and giving guidelines that we hope will help the organic chemist to make the most of the chemistry the Ph₂PO group has to offer.     

Theoretical and experimental study of triphenylphosphonium Schiff base of 5-hydroxy-3-methyl-1-phenyl-4-formylpyrazole

The Schiff base (HLBr), containing a chelating unit and triphenylphosphonium moiety has been synthesized in the reaction of 4-aminobenzyl(triphenyl)phosphonium bromide with 5-hydroxy-3-methyl-1-phenyl-4-formylpyrazole. The composition and structure of HLBr have been determined by elemental analysis, IR, 1D and 2D NMR, electronic spectroscopy and mass spectrometry. Density functional theory (DFT) calculations (6-311G(d,p) level of theory) have been carried out to investigate tautomeric forms of HL⁺ and the reaction mechanism of its formation and spectral properties. The most stable form in the solid state and in DMSO solution is pyrazolone (keto-amine) tautomeric form.     

Behavior of 1,1-diphenyl-2,5-dihydrophospholium salts toward bases: Ylide formation or ring opening

Efficient procedures are described leading to pure 3,4-R¹, R²-substituted 1,1-diphenyl-2,5-dihydrophospholium salts (R¹ = R² = CH₃, H; R¹ = CH₃, R² = H). Their behaviors toward bases such as nBuLi and tBuOK in THF or DMSO have been examined. According to the nature of the substituents R¹ and R², the complete monodeprotonation of these salts leads either to the corresponding pure five-membered cyclic ylide (and, in some cases, its prototropic isomer) or to a dienylphosphine resulting from a ring opening. The reactivity of the 3,4-dimethyl-disubstituted salt was especially studied. The corresponding monoylide functions as a good Wittig reagent, allowing stereoselective access to interesting alkadienylphosphine oxides and subsequently to trienes. However, in the presence of alkylating electrophiles, it reacts under an open dienylphosphine form giving rise to P-alkylated phosphonium salts. Nevertheless, this monoylide does not undergo further deprotonation into the corresponding cyclic diylide. Most of the synthetisized derivatives are original. © 1996 John Wiley & Sons, Inc.     

New anionic species of tellurium(IV)

Tetrahaloaryltellurates(IV) were prepared by refluxing aryltellurium trihalides with phosphonium, tropylium and telluronium halides in CHCl₃. These compounds, which contain the ArTeX^?₄ anion, may be also prepared from aryltellurium trihalides and aqueous halogen hydride solutions. The phosphonium derivatives can be considered as potential precursors of tellurophosphoranes for Wittig reactions. Halogen exchange reactions allow the interconversion of the complex anions. The ionic nature of the compounds is supported by ion exchange reactions utilizing ion exchange resins, and by conductance measurements. Far infrared and Raman spectral data suggest a square pyramidal configuration for the ArTeX^?₄ anions.     

Reactions of tautomeric quaternary phosphonium salts based on triphenylphosphine and 3-phenylpropargyl bromide with nitrogen nucleophiles

Triphenyl(3-phenylprop-1-ynyl)phosphonium bromide (3) was isolated. This compound is a third isomer for the tautomeric system triphenyl(3-phenylpropadienyl)phosphonium bromide (1) triphenyl(3-phenylprop-2-ynyl)phosphonium bromide (2). Salts 1 and 2 smoothly react with secondary amines to give adducts with an ,-double bond, while salt 3 changes to an allene ylide. Addition of phenylhydrazine and triphenyl(phenylethynyl)phosphonium bromide to salts 1 and 2 and addition of dimethylformamide to salt 2 were performed.     

The Preparation of Immunosuppressant SR-31747

The preparation of immunosuppressant SR-31747 is described. Attempts to install the Z-allyl amine included Lindlar partial hydrogenation and vinyl stannane methodologies. Ultimately, the Wittig olefination of aldehyde 12, with the ylide derived from β-aminoethyl phosphonium salt 13 proved successful.     

Reactivity of phosphonium diylids with esters and amides

The phosphonium diylid (C₆H₅)₂P(CH₂)(CH₂Li) reacts readily with various esters and amides to give acylated phosphonium salts and Wittig products. In the case of N,N-dimethylbenzamide the reaction can be directed mainly to the Wittig products by protonation. Depending on the nature of the carbonyl group, unexpected reactions, such as conjugate additions to α,β-unsaturated compounds or enolization of α-hydrogenated amides, can also take place.     

The preparation and reactions of group IIB metal chloride stabilized complexes of (chlorofluoromethylene)tris(dimethylamino)phosphorane

A facile dechlorination reaction occurs between [((CH₃)₂N)₃⁺PCFCl₂]Cl^? and Group IIB metals to form addition complexes of the type [((CH₃)₂N)₃P⁺ CFCl-(MCl)]Cl^? where M = Zn, Cd, or Hg. These complexes exhibit surprising stability in ethereal solvents, and serve as effective 1-chloro-1-fluorovinyl transfer agents via the Wittig reaction by dissociation into [(CH₃)₂N]₃PCFCl and the metal chloride. ¹⁹F and ³¹P NMR, as well as derivative formation, substantiate that these complexes are indeed quaternary phosphonium compounds which contain covalent carbonmetal bonds.     

Construction of Extended and Polymeric 1,3-Dithiolane and Tetrathiafulvalene Derivatives using Cycloaddition of Bun 3P.CS2

Abstract

Cycloaddition of the adduct between Buⁿ ₃P and CS₂ to strained double bonds such as in norbornene gives novel zwitterionic products such as 5. This dissociates to the ylide 4 so that carrying out the reaction in the presence of an aldehyde leads to a Wittig reaction to give 2-alkylidene-1,3-dithiolanes. The compound 5 reacts with acetylenic dipolarophiles by cycloaddition accompanied by loss of Buⁿ ₃P to give dihydro-TTF derivatives. Both these reaction types also occur for norbornadiene and by using this together with dialdehydes or diacetylenes a range of new sulfur-rich extended and polymeric structures have been obtained.     

1-Aminoalkylphosphonium Derivatives: Smart Synthetic Equivalents of N-Acyliminium-Type Cations,and Maybe Something More: A Review

N-acyliminium-type cations are examples of highly reactive intermediates that are willingly used in organic synthesis in intra- or intermolecular α-amidoalkylation reactions. They are usually generated in situ from their corresponding precursors in the presence of acidic catalysts (Brønsted or Lewis acids). In this context, 1-aminoalkyltriarylphosphonium derivatives deserve particular attention. The positively charged phosphonium moiety located in the immediate vicinity of the N-acyl group significantly facilitates C_α-P⁺ bond breaking, even without the use of catalyst. Moreover, minor structural modifications of 1-aminoalkyltriarylphosphonium derivatives make it possible to modulate their reactivity in a simple way. Therefore, these types of compounds can be considered as smart synthetic equivalents of N-acyliminium-type cations. This review intends to familiarize a wide audience with the unique properties of 1-aminoalkyltriarylphosphonium derivatives and encourage their wider use in organic synthesis. Hence, the most important methods for the preparation of 1-aminoalkyltriarylphosphonium salts, as well as the area of their potential synthetic utilization, are demonstrated. In particular, the structure–reactivity correlations for the phosphonium salts are discussed. It was shown that 1-aminoalkyltriarylphosphonium salts are not only an interesting alternative to other α-amidoalkylating agents but also can be used in such important transformations as the Wittig reaction or heterocyclizations. Finally, the prospects and limitations of their further applications in synthesis and medicinal chemistry were considered.     

An efficient synthesis of chiral terminal 1,2-diamines using an enantiomerically pure [1-(1′R)-methylbenzyl]aziridine-2-yl]methanol

Enantiomerically pure terminal 1,2-diamines, which can serve as precursors for the synthesis of many biologically important compounds, were synthesized efficiently from a commercially available chiral [1-(1′R)-methylbenzyl]aziridine-2-yl]methanol. Various enantiomerically pure 2-vinylaziridines were prepared by Wittig reactions from aziridine-2-carboxaldehyde and the corresponding phosphonium salts. The C(2)-N bond of the vinyl substituted aziridine ring was regioselectively cleaved by azidotrimethylsilane (TMSN₃). The azido group and the double bond were reduced successively to give the target compounds in high yields.     

Synthesis and structure of cobalt complexes [Ph3(n-Pr)P 2+ [CoI4]2? and [Ph3(n-Am)P 2+ [CoI4]2?

Complexes Ph₃(n-Pr)P₂⁺[CoI₄]²⁻ (I) and [Ph₃(n-Am)P]₂⁺ [CoI₄]²⁻ (II) were synthesized by reactions of triphenyl(alkyl)phosphonium iodide with cobalt(II) iodide in acetone. According to the X-ray diffraction data, complexes I and II consist of tetrahedral triphenyl(alkyl)phosphonium cations (for I, P-C is 1.787(4)–1.804(4) ? and CPC is 106.73(18)°–111.4(18)°; for II P-C is 1.786(6)–1.802(6) ? and CPC is 107.6(3)°–111.7(3)°) and [CoI₄]²⁻ anions (Co-I 2.5923(6)–2.6189(6) ?, ICoI 101.86(2)°–113.25(2)° for I; Co-I 2.5899(9)–2.6171(9) 107.01(3)°–110.47(3)° for II).     

Preparation,Reactions, and NMR Studies of 4-Methyl-4-Phospha-Tetracyclo [3.3.0.02,8.03,8] Octane 4-Oxide and Derivatives

Abstract

The title compound which we¹ and others² have previously synthesized has now been extensively investigated. The tetracyclic phosphonium chloride 1 was prepared by treatment of norbornadiene with CH₃PCl₂ at 65–80°C for one week. Treatment of 1 with AICl₃/CH₂CI₂ gave 2. Direct or “Inverse” addition at water to 2 dictated the stereochemistry of the oxide 3. Stereoassignments of 3 were made based on lanthanide shift ?¹H and ¹³C nmr studies studies. Extensive 2-D nmr studies (HETCOR, COSY) and triple irradiation experiments enabled chemical shift and coupling constant assignments.     

A sterically congested cis‐stilbene and its phosphonium salt precursor

Triphenyl(2,4,5‐trimethoxybenzyl)phosphonium chloride is formed in solvent‐free form by the reaction under anhydrous conditions between triphenylphosphane and 2,4,5‐trimethoxybenzyl chloride, but when it is crystallized from a mixture of ethyl acetate and chloroform in the presence of air it forms a stoichiometric monohydrate, C₂₈H₂₈O₃P⁺·Cl⁻·H₂O, (I). The reactions between the anhydrous phosphonium salt and alkoxy‐substituted benzaldehydes, using Wittig reactions in the presence of potassium tert‐butoxide, provide a series of multiply substituted stilbenes, most of which were assigned the Z configuration on the basis of their NMR spectra. However, no such deduction could be made for the symmetrically substituted (Z)‐2,2′,4,4′,5,5′‐hexamethoxystilbene, C₂₀H₂₄O₆, (II). Compound (II) does in fact have the Z configuration and the molecular geometry provides evidence for steric congestion around the central double bond; in particular, the central alkene fragment is nonplanar, with a C—C=C—C torsion angle of 7.8 (4)°. In hydrated salt (I), the chloride anions and water molecules are linked by O—H...Cl hydrogen bonds to form C₂¹(4) chains; each cation is linked by C—H...O hydrogen bonds to two different chains, so forming a sheet structure. There are no direction‐specific intermolecular interactions in the structure of (II).     

The Stereoselective Synthesis of Conjugated Allylsilanes

2-trimethylsilylethylidenetriphenylphosphorane (5) (Seyferth–Wittig reagent) reacts stereoselectively with the carbonyl compounds 6a–f to give the conjugated allylsilanes 7a–f, each as a mixture of E-and Z-isomers. The stereoselectivity of reactions of E-cinnamaldehyde (6c) with 5 has been investigated at different temperatures. A successful E-stereoselective synthesis of 7c was achieved by reacting 5 with E-cinnamaldehyde (6c) under the conditions of a Wittig–Schlosser modification reaction. Structures of the allylsilanes 7a–f were deduced by compatible analytical and spectroscopic (IR, ¹H NMR, ¹³C NMR, and GC/MS) measurements. An assignment of the E:Z ratios of 7a–f is based on their ¹H NMR spectral data.     

New and Stereospecific Synthesis of α-Ethylenic Ketones

Abstract

H. Kise et al¹ have shown that the reaction of β-propiolactones 1 with ylides 2 give phosphonium carboxylate betaïne 3. We now report that, carried out under different conditions, reaction of lactones 1 with the same ylides proceeds through pathway (b). Thermolysis of 4 affords α-ethylenic ketones 5. The mecanism of this new extrusion reaction of triphenylphosphine oxyde probably involves the generation of an oxaphosphene as an intermediate.     

Synthesis and characterization of novel benzoxazine-based arylidinyl succinimide derivatives

1,4-Benzoxazine skeleton holds substantial promise for further exploration owing to its immense pharmacological potential. In this pursuit, a series of 20 novel benzoxazine-based arylidinyl succinimide derivatives (23–42) were synthesized in moderate to good yields by the reaction of ethyl 2-(7-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-3-oxo-2H-benzo[b][1,4]oxazin-4(3H)-yl)acetate (22) with various aromatic aldehydes under Wittig reaction conditions in the presence of triphenylphosphine and ethanol. All these synthesized compounds were fully characterized from their spectral data (¹H, ¹³C, and ²D NMR, IR, UV, high-resolution mass spectroscopy (HRMS)) and further confirmed by X-ray crystallographic analysis of a representative compound (32). Antibacterial activity of obtained arylidinyl succinimide derivatives was evaluated against both Gram-positive and Gram-negative bacterial strains and were found to exhibit insignificant activity as compared to the reference.     

Synthesis of stilbene analogues by one-pot oxidation-Wittig and oxidation-Wittig-Heck reaction

Synthesis of symmetrical (and unsymmetrical) stilbene derivatives is achieved by a combination of one-pot steps of Kornblum type oxidation of benzyl halide, its simultaneous in situ formation of phosphonium salt, and subsequently their Wittig reaction. In other variant it is oxidized to aldehyde, treated with ylide generated from phosphonium salt (CH₃PPh₃X) to give styrene, and subjected to Pd catalyzed Heck reaction with arylhalide to give stilbenes as the three-step one-pot sequence.