Wiesława Perlikowska

Optically active trivalent phosphorus compounds—I: Diastereoisomeric o-menthyl ethylphenylphosphinites: synthesis, chirality at phosphorus and stereochemistry of nucleophilic displacement reaction

Abstract The reaction between racemic ethylphenylchlorophosphine and menthol has been found to give a mixture of diastereoisomeric O-menthyl ethylphenylphosphinites (4) in unequal ratio. The diastereoisomeric content depends mainly on the tertiary amine used for the condensation. The chirality at phosphorus in the diastereoisomeric esters (4a and 4b) has been assigned by means of chemical correlation (conversion into optically active methylethylphenylphosphine oxide) and proton NMR spectra. It has been demonstrated that nucleophilic substitution at phosphorus in 4 occurs with inversion of configuration.

Kinetic resolution of P-chiral tertiary phosphines and chlorophosphines: a new approach to optically active phosphoryl and thiophosphoryl compounds †

Abstract— Treatment of racemic P-stereogenic tertiary phosphines with enantiomerically pure bis-phosphoryl and bis-thiophos-phoryl disulfides under kinetic resolution conditions (2:1 ratio) afforded enantiomerically enriched tertiary phosphine oxides orphosphine sulfides with ee values up to 39%. In a similar way from racemic tert -butylphenylchlorophosphine, optically active tert -butylphenylphosphinoyl chloride with 50% ee was obtained. The same reaction performed under dynamic kinetic resolutionconditions (1:1 ratio of reagents) in the presence of chloride ions gave phosphinoyl chloride with 70% ee.

Stereospecific synthesis of diastereoisomerically pure (–)-(Rp)-O-menthyl methylphenylphosphinite and ethylphenylphosphinite: key intermediates in synthesis of chiral tertiary phosphines

The reaction of the diastereoisomerically pure (–)-(RP)-O-menthyl methylphenylphosphinite (9) and (–)-(RP)-O-menthyl ethylphenylphosphinite (2) with organolithium reagents has been found to give chiral tertiary phosphines (10) and (11) with a very high optical purity.

Synthesis of 1-diethoxyphosphoryl-1-methylthio-thioacetamides and 1-methylthioethenethioamides. An unusual intramolecular α-desulfenylation of thioacetamides

Abstract Addition of the lithiated α-phosphoryl sulfide 1-Li to alkyl or aryl isothiocyanates 4(a–f) and phenyl isocyanate 4g was found to afford 1-diethoxyphosphoryl-1methylthio-thioacetamides 5(a–f) and -acetamide 5g , respectively. In the case of the reaction with the p-chlorophenyl isothiocyanate 4e , the α-desulfenylated product 6 was isolated and on the basis of 31 P-NMR experiments a mechanism of its formation was proposed. The phosphonates 5(a–f) , which exist in the thione form, were found to undergo the Horner-Wittig reaction with aromatic aldehydes affording 1-methylthioethenethioamides 14(a–f) .

A NEW ENANTIOSELECTIVE ASYMMETRIC SYNTHESIS OF TRI-CO-ORDINATE PHOSPHORUS COMPOUNDS FROM DI-CO-ORDINATE λ3-ARYL(ALKYL)IMINOPHOSPHINES

Abstract The reaction of di-co-ordinate λ3-aryl(alkyl)iminophosphines (1) with achiral alcohols in the presence of optically active tertiary amines has been found to proceed in an asymmetric way affording optically active O-alkyl amidophosphonites (2). N-(2,4,6-Tris-t-butylphenyl)amido-O-methyl-phenyl-phosphonite (2a) was obtained in this way with 55% ee and the absolute configuration (S) was chemically linked with (+)-(R)-O-methyl t-butanephosphonothioic acid.

Horner Olefination Reaction in Organic Sulfur Chemistry and Synthesis of Natural and Bioactive Products

This article outlines the results of our work on the application of the Horner olefination reaction for the synthesis of unsaturated sulfur compounds. A general synthesis of racemic and optically-active α,β-unsaturated sulfoxides by the Horner reaction with α-sulfinylmethylphosphonates as olefination reagents is presented. We demonstrated how the structure of the phosphonate moiety may control the E- and Z-stereoselectivity in the above reaction. The use of racemic and optically-active α-sulfinylvinylphosphonates in tandem Michael addition/Horner olefination reaction leads to a wide range of carbocyclic and heterocyclic vinyl sulfoxides. In second part of this account a new strategy for the synthesis of functionalized cyclopentenones is briefly described. The synthesis and reactivity of 3-phosphorylmethyl-cyclopentenones is discussed as a platform for developing the synthesis of racemic rosaprostol, enantiomeric prostaglandin B1 methyl esters, enantiopure isoterreins, natural and unnatural neplanocin A and enantiomeric forms of phytoprostane B 1 type I.

A new and expeditious synthesis of all enantiomerically pure stereoisomers of rosaprostol, an antiulcer drug

Summary Four enantiomerically pure stereoisomers of rosaprostol (1), an antiulcer drug, were efficiently synthesized from the enantiomers of 2-(dimethoxyphosphoryl)-3-hexylcyclopentanone (3) as chiral substrates. The latter were obtained by resolution of racemic 3 with (+)-(R)-1-(1-naphthyl)ethylamine. The conversion of (+)-3 into rosaprostol stereoisomer (−)-1a was accomplished in four steps in 56% overall yield. According to the same protocol, the second stereoisomer (+)-1c was obtained from (−)-3 in 55% overall yield. A slightly improved procedure of the last two steps of the transformation of (+)-3 into (−)-1a allowed an increase in the overall yield to 64%. The remaining two stereoisomers, (−)-1b and (+)-1d, were obtained from (−)-1a and (+)-1c in 71 and 68% yield, respectively, by a two-reaction sequence, in which a Mitsunobu inversion of configuration at C-5 was the key step.

Synthesis of Enantiomerically Pure Stereomers of Rosaprostol.

Enantiopure stereomers of rosaprostol 1, an antiulcer drug, were synthesized from diastereomeric building blocks (-)-5a and (+)-5b. Conversion of (-)-5a into rosaprostol stereomer (-)-(1S,2R,5R)-1a was accomplished in nine steps in 18% overall yield. In this sequence, fully diastereoselective hydrogeneration of the endocyclic carbon double bond in the cyclopentenone ring was key, generating a new stereogenic center (C-2 in 1a). C-5 epimeric rosaprostol (-)-(1S,2R,5S)-1b was obtained from (-)-1a in 72% yield by a two-reaction sequence involving methylation and one-pot Mitsunobu esterification-hydrolysis.

THE E⇌Z ISOMERIZATION OF 1-METHYLSULFANYLPROPENOIC N-ARYLTHIOAMIDES

Abstract 1-Methylsulfanylpropenoic N-arylthioamides 2 were shown to undergo the two way F/Z isomerization triggered by heat, light and the oxygen and sulfur nucleophiles.

Diasteredmeric Alkylphenylphdsphinic Acids Derivatives Containing Menthyl, Thionedmenthyl and Aminomenthyl Groups: Synthesis, Chirality and Applications

Abstract Recently we have found1 that the condensation of racemic alkylphenylphosphinochloridite with menthol affords a mixture of diastereomers. We have also demonstrated utility of this reaction f o r the synthesis of optically active phosphines and amides1,2. In this communication we present application of neomenthanethiol and menthaneamine as chiral auxiliaries inducing optical activity at the phosphorus atom.