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.     

The reaction of Wittig and Wittig–Horner reagents with dicyanomethylene derivatives of fluorenone,xanthone, and thiaxanthone. A novel synthesis of phosphoranylidenecyclobutylidene derivatives

>Wittig reagents 1a,b react with dicyanomethylene derivatives of fluorenone (3) and xanthone (4) to give the corresponding phosphoranylidenecyclobutylidene adducts 6a, 6b, 9a, and 9b. On the other hand, the reaction of Wittig–Horner reagents (2) with the same nitriles 3 and 4 afforded the respective phosphonate adduct 8 and the alkylated product 10. A mechanism that accounts for the formation of the new products is presented. © 1999 John Wiley & Sons, Inc. Heteroatom Chem 10: 263–269, 1999     

The reactions of Wittig–Horner reagents with 1,3-dioxo-Δ2,α-indanmalononitrile

Wittig–Horner reagents ( 1a–e ) react with 1,3-dioxo-Δ^2,α-indanmalononitrile ( 2 ) to give the phosphonate adducts 3, 4, 5, 6, and 7 , respectively. Structural reasoning for the new products was based on compatible analytical and spectral data (IR, ¹H, ³¹P NMR, and MS). The mechanism that accounts for the formation of the new adducts is discussed. © 1997 John Wiley & Sons, Inc. Heteroatom Chem 8 : 253–257, 1997.     

Synthesis,characterization, and antitumor evaluation of 4-aminoximidofurazan derivatives

Reactions of 3-amino-4-aminoximidofurazan (AAOF) with Wittig–Horner reagents, trialkylphosphites, trisdialkylaminophosphines as well as the thiating Lawesson and Japanese reagents were studied. Elemental analysis and spectroscopic measurements were in good accord with the structures postulated for the new products. The antitumor activities of certain selected new compounds were screened, in vitro, against a panel of five (liver; HepG2; breast; MCF-7; lung; A549; colon; HCT116; and prostate PC3) human solid tumor cell lines.     

The synthesis and reactivity of alkyl‐aminosubstitutedmethylenediphosphonates

Reactions of diethyl phosphite with Vilsmeier reagents, RCONR¹R²/POCl₃, afforded various alkylaminosubstitutedmethylenediphosphonates in acceptable yields, which (R = H) were then reacted with aldehydes under the conditions of the Wittig–Horner reaction to furnish vinylphosphonates, and which (R = H) underwent alkylation with alkyl halides to give alkylaminosubstitutedmethylenediposphonates 8 . (Z)‐Vinylphosphonates could be converted to (E)‐isomers in refluxing ethyl acetate.© 1999 John Wiley & Sons, Inc. Heteroatom Chem 10: 271–276, 1999     

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.     

Reaction of 2-Thioxo-4-Thiazolidinones Toward Lawesson's Reagent,Phosphorus Pentasulfide,Dialkylaminophosphines, and Phosphorus Ylides

Abstract

2-Thioxo—3-allyl-4-thiazolidinone 1a reacts with Lawesson's reagent (LR, 2) to give the ethylenic product 5 through a coupling reaction along with the dithioxo compound 6. Coupling reaction products of types 8 and 9 are also produced upon reacting thiazolidinones 1 and with the appropriate tris(diallkylamino) phosphine reagent (3 a,b). Reaction of the thiazolidinone 1a with the ylidenetriphenylphosphorane reagents 4 a–c proceeds according to the Wittig mechanism yielding ethylenes 10a–c, respectively. Structural elucidations for the new products were based upon compatible analytical and spectroscopic measurements as well a confirmatory single crystal X-ray structure for 5.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the related elements to view the free supplemental file.     

The behavior of 2‐substituted‐1,3‐diphenylpropane‐1,3‐tione toward organophosphorus reagents

The reaction of 2‐benzylidene‐1,3‐diphenylpropanetrione ( 1a ) with phosphorus ylides 2a–c afforded the new phosphonium ylides 4a–c . Trialkyl phosphites 3a–c react with 1a to give the respective dialkyl phosphonate products 5a–c . On the other hand, the olefinic compounds 6 and 7 were isolated from the reaction of 1b with Wittig reagents 2 . Moreover, trialkyl phosphites reacted with 1b to give products 8a–c . Possible reaction mechanisms are considered, and the structural assignments are based on analytical and spectroscopic evidence. © 2000 John Wiley & Sons, Inc. Heteroatom Chem 11:57–64, 2000     

Organophosphorus chemistry 23 [1], the reaction of α,β-unsaturated nitriles with alkyl phosphites and phosphorus ylides

Wittig reagents 2 react with furfurylidenemalonitrile ( 1a ) and thienylidenemalonitrile ( 1b ) to give a mixture of products ( 6 and 7 ). Compound 1b reacts with di-alkyl phosphites ( 3 ) and trialkyl phosphites ( 4 ) to give the phosphonate 1:1 adducts 9 and 12 , respectively. Structures of the new products were confirmed on the basis of elemental analyses and spectral studies.     

Synthesis and Characterization of Novel Stilbene Derivatives with 1,3,4‐Oxadiazole Unit

Four novel stilbene derivatives containing 1,3,4‐oxadiazole unit have been synthesized in four steps with overall yields (27～35%). The synthetic route involved one‐step installation of 2,5‐di‐p‐tolyl‐1,3,4‐oxadiazol via the direct coupling of p‐toluic acid with hydrazine hydrate promoted by PPA , benzylic bromination, conventional phosphonate formation, and Wittig‐Horner olefination.     

Synthesis and photophysical properties of benzo[c]thiophene,p-phenylene-, triphenylamine-, and pyrene-based vinylenes

An efficient synthesis of benzo[c]thiophenyl/p-phenylenyl/pyrenyl phosphonate esters has been achieved using ZnBr₂-catalyzed Michaelis–Arbuzov reaction of corresponding benzyl alcohol/bromides at room temperature. Horner–Wadsworth–Emmons reaction of the phosphonate esters with aryl/heteroaryl aldehydes in the presence of t-BuOK furnished the vinylenes in good yields. The absorption and emission characteristics of the synthesized vinylenes were also reported.     

STUDIES ON PHOSPHONIUM YLIDES-XII. THE REACTION OF STABLE PHOSPHORANES WITH HEXAHYDRO-1,3-PHTHALANDIONE

Abstract

Wittig reagents (Ia-c) react with hexahydro-1,3-phthalandione (II) yielding the new adducts (IIIa-e). The structure of these products were established by analytical and spectroscopic methods. A mechanism is proposed to explain the formation of the new ylid-phosphorane adduct IIIa.     

Synthesis and stereoselectivity of a new type of unsaturated phosphonates

A series of unsaturated phosphonates 2, 3, 4 with structures similar to that of abscisic acid (ABA) were synthesized by the Wittig‐Horner reactions of bisphosphonylmethane 1 with β‐substituted propenals, propargyl aldehydes or α,β‐unsaturated methyl ketones. Compounds 5 were prepared by the Michaelis‐Becker reactions of ω‐bromodienes 7 with sodium phosphites. Compounds 7 were obtained by the phase transfer Wittig reactions of ω‐bromobutylphosphonium salt 6 with β‐substituted propenals. The structures of all new compounds prepared were characterized by ¹H NMR, ³¹P NMR, IR spectra, and elemental analysis or MS. The stereochemistry of the Wittig reactions was studied. © 2000 John Wiley & Sons, Inc. Heteroatom Chem 11:261–266, 2000     

Unusual Course of the Reaction of Allyl Phosphine Oxides with the Grundmann Ketone

This article describes efficient preparation of isomeric allyl phosphine oxides possessing a protected cyclohexanediol fragment. Their base-catalyzed interconversions are examined and reactions with the Grundmann ketone provide an adduct containing the rearranged vinyl phosphine oxide moiety, instead of 19-norvitamin D₃ analogs, the expected products of the Horner–Wittig process.     

Olefination of methyl (1S,2R,4R)-N-benzoyl-2-formyl-7-azabicyclo[2.2.1]heptane-1-carboxylate,a synthetic approach to new conformationally constrained prolines

Wittig olefinations of methyl (1S,2R,4R)-N-benzoyl-2-formyl-7-azabicyclo[2.2.1]heptane-1-carboxylate with several phosphoranes and the Horner–Wittig reaction, using methyl diethylphosphonoacetate, have been tested in order to evaluate their utility in the synthesis of β-substituted conformationally constrained prolines. Subsequent elaboration of the resulting alkenes has provided proline–amino acid chimeras [combinations of proline with other α-amino acids, such as l-norvaline, l-norleucine, l-α-(3-phenylpropyl)glycine or l-homoglutamic acid] with the 7-azabicyclo[2.2.1]heptane skeleton in an enantiomerically pure form.     

Reactions of phosphite esters and trisdialkylaminophosphines with 5‐substituted 1,3,4‐thiadiazol derivatives

5‐{[(1E)‐(4‐methoxyphenyl)methylene]amino}‐1,3,4‐thiadiazole‐2‐thiol ( 1a ) reacts with trialkyl phosphites ( 2a–c ) to give the respective dialkyl phosphonate adducts ( 4a–c ). On the other hand, the reactions of trisdialkylaminophosphines ( 3a,b ) with 1a , 5‐{[(1E)‐(4‐phenyl)methylene]amino}‐1,3,4‐thiadiazole‐2‐thiol ( 1b ) yield the corresponding open dipolar structures 6a–c . In the case of the reaction of triethyl phosphite ( 2a ) with 1b , both the dialkyl phosphonate adduct ( 7 ) and the dipolar product ( 8a ) are obtained. Moreover, triisopropyl phosphite ( 2c ) reacts with 1b to give both the S‐alkyl and the N‐alkyl phosphonate adducts ( 9a,b ), respectively. Mechanisms are proposed to explain the formation of the new products, and their structures were confirmed on the basis of elemental analysis and spectral studies. © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:594–601, 2001     

The Synthesis of New S- and N,S-Substituted Halo Nitro Dienes by the Reactions of 1-Bromo-1,2,4,4-tetrachloro-3-nitrobuta-1,3-diene with Thiols and Cyclic Amines

The substituted products alkyl(aryl)thio-tetrahalo-3-nitrobuta-1,3-dienes 3a–b were obtained from the reactions of 1-bromo-1,2,4,4-tetrachloro-3-nitrobuta-1,3-diene (1) with thiols. Further reactions of the substituted product alkyl(aryl)thio-tetrahalo-3-nitrobuta-1,3-dienes 3a–b in dichloromethane reacted with piperazine derivatives and morpholine to generate 5a–b and 7a–l. The structures of the new compounds were determined by microanalysis and spectroscopic data.     

Synthesis,Characterization, and Antimicrobial Evaluation of Some Novel 4-Hydroxyquinolin-2(1H)-ones

Vilsmeier–Haack formylation of 3-acetyl-1-methyl-4-hydroxyquinolin-2(1H)-one (2) produced the novel 6-methyl-4,5-dioxo-5,6-dihydro-4H-pyrano[3,2-c]quinoline-3-carboxaldehyde (3). Reactions of carboxaldehyde 3 with a diversity of nucleophilic reagents were studied and a variety of products were obtained via ring-opening, ring-closing (RORC) sequence. Also, some novel heteroannulated pyrano[3,2-c]quinolines were prepared. Structures of the new synthesized products were deduced on the basis of their analytical and spectral data.     

Application of Horner–Emmons Olefination to the Crown-Ether Derivatives

An effective synthetic approach to the preparation of a new crown-ether vinylogs involving the Horner–Emmons olefination of carbonyl precursors with the use of C₂- and C₅-phosphonates was proposed. The effects of the conjugation chain length and the nature of the terminal polar functions in the phosphonate reagent on the yield and process stereoselectivity were discussed.     

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%.