Wanda H. Midura

Asymmetric cyclopropanation of chiral (1-dimethoxyphosphoryl-2-phenyl)vinyl p-tolyl sulfoxide: a new synthesis of enantiomerically pure 2-amino-3-phenyl-1-cyclopropane-phosphonic acid—a constrained analog of phaclofen

Abstract E -( S )-(1-Dimethoxyphosphoryl-2-phenyl)vinyl p -tolyl sulfoxide 3 was found to undergo cyclopropanation with sulfur ylides [dimethyl(oxo)sulfonium methylide, diphenyl sulfonium isopropylide and ethyl (dimethylsulfuranylidene)acetate (EDSA)] in a highly diastereoselective manner. The major diastereomer obtained in the reaction of E -( S )- 3 with EDSA was converted into enantiopure (2 R )-amino-(3 R )-phenyl-(1 R )-cyclopropane-phosphonic acid, a constrained analog of the GABA B antagonist, phaclofen.

1,3-Dipolar cycloaddition of diazoalkanes to racemic and optically active α-(diethoxyphosphoryl)vinyl p-tolyl sulfoxides: a new synthesis of 3-phosphorylpyrazoles and asymmetric synthesis of cyclopropanes

Abstract Cycloaddition of diazomethane and ethyl diazoacetate to α-(diethoxyphosphoryl)vinyl p-tolyl sulfoxide 1a and its β-substituted analogues (Me, Ph) results in the formation of 3-phosphoryl-pyrazoles in high yield. The reaction ofchiral (S)-(+)-1a with diphenyldiazomethane proceeds fully diastereoselectively to give the corresponding cyclopropane (+)-6a with the (Sc, SS) configuration determined by X-ray diffraction analysis. Diazopropane reacts with (S)-(+)-1a to give only one diastereoisomer of the pyrazoline cycloadduct (+)-2e which undergoes decomposition to the cyclopropane (+)-6b with preservation of configurational integrity.

The first synthesis of enantiomerically pure cyclopropylphosphonate analogues of nucleotides via asymmetric cyclopropanation of chiral (1-diethoxyphosphoryl)vinyl p-tolyl sulfoxide

(S)-(+)-(1-Diethoxyphosphoryl)vinyl p-tolyl sulfoxide undergoes cyclopropanation with ethyl (dimethylsulfuranylidene)acetate (EDSA) in a highly diastereoselective manner (facial stereoselectivity up to 12:1). The major diastereomer obtained in this reaction, (1S,2S)-(1-diethoxyphosphoryl-2-ethoxycarbonyl)cyclopropyl p-tolyl sulfoxide, was converted in three steps into enantiopure cyclopropylphosphonate analogues of purine nucleotides as the constrained forms of antiviral 1-alkenylphosphonic acid derivatives of purines.

(+)-(S)-α-diethoxyphosphorylvinyl p-tolyl sulfoxide: A new chiral Michael acceptor and dienophile

Abstract The tittle reagent, (+)-(S)-1, was prepared from (+)-(S)s-α-diethoxy-phosphorylethyl p-tolyl sulfoxide 2 by phenylselenylation-deselenylation procedure. Its reactivity was demonstrated by diastereoselective Michael addition of ethanethiol giving rise to 3, tandem Michael addition/intramolecular Horner--Wittig reaction with 2-formyl pyrrole leading to the corresponding pyrrolizine sulfoxide 5 and cycloaddition with cyclopentadiene affording the diastereomeric adducts 6. The steric course of the Diels-Alder reaction is briefly discussed.

Phosphonates containing sulfur and selenium: The first synthesis of α-phosphorylvinyl selenides and selenoxides and a new synthetic approach to alkynylphosphonates

Abstract An efficient, two-step synthesis of α-phosphorylvinyl selenides 4 from α-phosphoryl sulfoxides 1 is described which involves selenenylation reaction and subsequent thermal sulfoxide elimination. Oxidation of 4 leads to α-phosphorylvinyl selenoxides 5 which upon thermolysis afford alkynylphosphonates 6 .

Synthesis of mono- and 1,4-dicarbonyl compounds based on the oxygenation of phosphonate carbanions. Synthesis of dihydrojasmone, allethrone and methylenomycin b☆

Abstract Oxidation of the α-alkylthio-substituted phosphonate carbanions was found to give the corresponding carbonyl compounds. A new synthesis of 1,4-dicarbonyl systems involving the oxygenation of phosphonate carbanions as a key step is described. Total synthesis of dihydrojasmone and allethrone and formal synthesis of methylenomycin B is reported.

α-Phosphoryl sulfoxides. VIII: Stereochemistry of α-chlorination of α-phosphoryl sulfoxides

Abstract Chlorination of α-phosphoryl sulfoxides 1 with iodobenzene dichloride and sulfuryl chloride in the presence and in the absence of pyridine and stereochemical investigations of this reaction using (+)-(S)-α-dimethoxyphosphorylmethyl p-tolyl sulfoxide 1a are described. It was found that conversion of 1 to the corresponding α-chloro-α-phosphoryl sulfoxides 2 occurs under the stereochemical control of the sulfinyl group and leads to diastereomeric mixtures. The extent of asymmetric induction at the α-carbon atom and racemization of the chiral sulfinyl centre in 1 depend on the reaction conditions. The structure of the major diastereomer formed in the chlorination of (+)-(S)-1ai.e. (+)-(S)c(S)s-α-chloro-α-dimethoxyphosphorylmethyl p-tolyl sulfoxide 2a was determined by X-ray analysis. The structure was solved by direct methods and refined to R=0.081. The experimental data on chlorination of α-phosphoryl sulfoxides 1 point to retention of the configuration at both chiral centres (C and S) and this stereochemistry can be rationalized assuming addition-elimination mechanism involving the formation of a positively charged ylide as intermediate.

α-Phosphoryl sulfoxides. XI. Sulfenylation of α-phosphoryl sulfoxides and a general synthesis of optically active ketene dithioacetal mono-S-oxides

Abstract Sulfenylation and selenenylation of α-phosphoryl sulfoxides 1 with S-methyl methanethiosulfonate and phenylselenenyl bromide, respectively, affording α-methylsulfenyl- and α-phenylselenenyl-α-phosphoryl sulfoxides 8 and 9 are described. Sulfenylation of (+)-(S)-dimethoxyphosphorylmethyl p-tolyl sulfoxide 2 gave a mixture of optically active diastereoisomers of the sulfoxide 8a which is a key substrate in the Horner-Wittig synthesis of enantiomeric ketene dithioacetal mono-S-oxides 10. The E Z ratio of geometrical isomers of 10 was determined and briefly discussed. The crystal and molecular structure of E-1-p-tolylsulfinyl-1-methylsulfenyl-2-phenyl-ethene 10a is reported.

ZUR SYNTHESE VON BIS-ALKYLMERCAPTO-METHANPHOSPHONSÄUREDIALKYLESTERN1,2

Abstract To find a simple and reproducible synthesis of bis-alkylmercaptomethane phosphonates 1 several methods had been examined. The reaction of chloro-dialkylmercaptomethanes 3 with trialkylphosphite (Method A) and the reaction of diethoxymethanphosphonate 8 with mercaptanes (Method F) proved to be the best methods. Fur eine einfache und reproduzierbare Synthese von Bis-alkylmercaptomethanphosphonsauredialkylestern 1 wurden eine Reihe von Methoden uberpruft. Hierbei erwiesen sich die Umsetzung von Chlor-dialkylmercaptomethan 3 mit Trialkylphosphit (Methode A) und die Umsetzung von Diethoxy-methanphosphonsauredialkylester 8 mit Mercaptanen (Methode F) als am geeignetsten.

α-phosphoryl sulfoxides. X. A general synthesis of optically active α-chlorovinyl sulfoxides

Abstract A general and efficient synthesis of enantiomeric α-chlorovinyl p-tolyl sulfoxides 1 using (+)-(S) C (S) S -α-chloro-α-dimethoxyphosphorylmethyl p-tolyl sulfoxide as a key substrate for the Horner-Wittig reaction with carbonyl compounds is described. The E Z ratio of geometrical isomers of 1 was determined and briefly investigated. The X-ray diffraction structures of ( Z )-1-chloro-1-p-tolylsulfinyl-2-phenyl-ethene and (Z)-1-chloro-1-p-tolylsulfinyl-2-(2-thienyl)-ethene are reported.