Organocatalytic stereoisomerization versus alkene isomerization: Catalytic asymmetric synthesis of 1-hydroxy-trans -2,5-diphenylphospholane 1-oxide

Lukas Hintermann, Marco Schmitz, Olegv Maltsev, Pance Naumov

Research output: Contribution to journalArticle

Abstract

The potential for an organocatalytic asymmetric stereoisomerization or alkene isomerization as atom-economic reaction with minimal structural change was investigated. The McCormack cycloaddition of 1,4-diarylbuta-1,3-dienes with (dialkylamino)dichlorophosphane and aluminum trichloride gives meso-2,5-diaryl-1-(dialkylamino)-1-oxo-2,5-dihydro-1H-phospholes, which were identified as suitable substrates for asymmetric isomerization to (1R,5R)-2,5-diaryl-1-(dialkylamino)-1-oxo-4,5-dihydro-1H-phospholes in the presence of bifunctional organocatalysts (cinchona alkaloids, Takemoto catalyst) in up to 91% ee and quantitative yield. The substrate range and the mechanism of the catalysis were studied. The reaction involves proton abstraction by the base, but a primary deuterium KIE is absent. Enriched (1R,5R)-1-(diethylamino)- 1-oxo-2,5-diphenyl-4,5-dihydro-1H-phosphole was hydrolyzed to (5R)-1-hydroxy-1-oxo-2,5-diphenyl-4,5-dihydro-1H-phosphole, which was hydrogenated diastereoselectively under dissolving metal conditions to give (2R,5R)-1-hydroxy-1-oxo-2,5-diphenylphospholane (Fiaud's acid) in preference to meso-1-hydroxy-1-oxo-2,5-diphenylphospholane. An asymmetric catalytic total synthesis of Fiaud's acid, which is a building block for chiral phospholane synthesis, has been realized in five steps from thiophene, using nickel-catalyzed Wenkert arylation, McCormack cycloaddition, asymmetric dihydro-1H-phosphole isomerization, hydrolysis, and diastereo-selective hydrogenation.

Original languageEnglish (US)
Article numberSS-2012-T0745-FA
Pages (from-to)308-325
Number of pages18
JournalSynthesis (Germany)
Volume45
Issue number3
DOIs
StatePublished - Jan 11 2013

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Alkenes
Isomerization
Oxides
Olefins
Cycloaddition
Cinchona Alkaloids
Thiophenes
Acids
Deuterium
Thiophene
Substrates
Nickel
Catalysis
Hydrogenation
Protons
Hydrolysis
Metals
Aluminum
Atoms
Economics

Keywords

  • asymmetric catalysis
  • heterocycles
  • isomerization
  • phosphorus
  • stereoselective synthesis

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

Cite this

Organocatalytic stereoisomerization versus alkene isomerization : Catalytic asymmetric synthesis of 1-hydroxy-trans -2,5-diphenylphospholane 1-oxide. / Hintermann, Lukas; Schmitz, Marco; Maltsev, Olegv; Naumov, Pance.

In: Synthesis (Germany), Vol. 45, No. 3, SS-2012-T0745-FA, 11.01.2013, p. 308-325.

Research output: Contribution to journalArticle

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abstract = "The potential for an organocatalytic asymmetric stereoisomerization or alkene isomerization as atom-economic reaction with minimal structural change was investigated. The McCormack cycloaddition of 1,4-diarylbuta-1,3-dienes with (dialkylamino)dichlorophosphane and aluminum trichloride gives meso-2,5-diaryl-1-(dialkylamino)-1-oxo-2,5-dihydro-1H-phospholes, which were identified as suitable substrates for asymmetric isomerization to (1R,5R)-2,5-diaryl-1-(dialkylamino)-1-oxo-4,5-dihydro-1H-phospholes in the presence of bifunctional organocatalysts (cinchona alkaloids, Takemoto catalyst) in up to 91{\%} ee and quantitative yield. The substrate range and the mechanism of the catalysis were studied. The reaction involves proton abstraction by the base, but a primary deuterium KIE is absent. Enriched (1R,5R)-1-(diethylamino)- 1-oxo-2,5-diphenyl-4,5-dihydro-1H-phosphole was hydrolyzed to (5R)-1-hydroxy-1-oxo-2,5-diphenyl-4,5-dihydro-1H-phosphole, which was hydrogenated diastereoselectively under dissolving metal conditions to give (2R,5R)-1-hydroxy-1-oxo-2,5-diphenylphospholane (Fiaud's acid) in preference to meso-1-hydroxy-1-oxo-2,5-diphenylphospholane. An asymmetric catalytic total synthesis of Fiaud's acid, which is a building block for chiral phospholane synthesis, has been realized in five steps from thiophene, using nickel-catalyzed Wenkert arylation, McCormack cycloaddition, asymmetric dihydro-1H-phosphole isomerization, hydrolysis, and diastereo-selective hydrogenation.",
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AU - Hintermann, Lukas

AU - Schmitz, Marco

AU - Maltsev, Olegv

AU - Naumov, Pance

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N2 - The potential for an organocatalytic asymmetric stereoisomerization or alkene isomerization as atom-economic reaction with minimal structural change was investigated. The McCormack cycloaddition of 1,4-diarylbuta-1,3-dienes with (dialkylamino)dichlorophosphane and aluminum trichloride gives meso-2,5-diaryl-1-(dialkylamino)-1-oxo-2,5-dihydro-1H-phospholes, which were identified as suitable substrates for asymmetric isomerization to (1R,5R)-2,5-diaryl-1-(dialkylamino)-1-oxo-4,5-dihydro-1H-phospholes in the presence of bifunctional organocatalysts (cinchona alkaloids, Takemoto catalyst) in up to 91% ee and quantitative yield. The substrate range and the mechanism of the catalysis were studied. The reaction involves proton abstraction by the base, but a primary deuterium KIE is absent. Enriched (1R,5R)-1-(diethylamino)- 1-oxo-2,5-diphenyl-4,5-dihydro-1H-phosphole was hydrolyzed to (5R)-1-hydroxy-1-oxo-2,5-diphenyl-4,5-dihydro-1H-phosphole, which was hydrogenated diastereoselectively under dissolving metal conditions to give (2R,5R)-1-hydroxy-1-oxo-2,5-diphenylphospholane (Fiaud's acid) in preference to meso-1-hydroxy-1-oxo-2,5-diphenylphospholane. An asymmetric catalytic total synthesis of Fiaud's acid, which is a building block for chiral phospholane synthesis, has been realized in five steps from thiophene, using nickel-catalyzed Wenkert arylation, McCormack cycloaddition, asymmetric dihydro-1H-phosphole isomerization, hydrolysis, and diastereo-selective hydrogenation.

AB - The potential for an organocatalytic asymmetric stereoisomerization or alkene isomerization as atom-economic reaction with minimal structural change was investigated. The McCormack cycloaddition of 1,4-diarylbuta-1,3-dienes with (dialkylamino)dichlorophosphane and aluminum trichloride gives meso-2,5-diaryl-1-(dialkylamino)-1-oxo-2,5-dihydro-1H-phospholes, which were identified as suitable substrates for asymmetric isomerization to (1R,5R)-2,5-diaryl-1-(dialkylamino)-1-oxo-4,5-dihydro-1H-phospholes in the presence of bifunctional organocatalysts (cinchona alkaloids, Takemoto catalyst) in up to 91% ee and quantitative yield. The substrate range and the mechanism of the catalysis were studied. The reaction involves proton abstraction by the base, but a primary deuterium KIE is absent. Enriched (1R,5R)-1-(diethylamino)- 1-oxo-2,5-diphenyl-4,5-dihydro-1H-phosphole was hydrolyzed to (5R)-1-hydroxy-1-oxo-2,5-diphenyl-4,5-dihydro-1H-phosphole, which was hydrogenated diastereoselectively under dissolving metal conditions to give (2R,5R)-1-hydroxy-1-oxo-2,5-diphenylphospholane (Fiaud's acid) in preference to meso-1-hydroxy-1-oxo-2,5-diphenylphospholane. An asymmetric catalytic total synthesis of Fiaud's acid, which is a building block for chiral phospholane synthesis, has been realized in five steps from thiophene, using nickel-catalyzed Wenkert arylation, McCormack cycloaddition, asymmetric dihydro-1H-phosphole isomerization, hydrolysis, and diastereo-selective hydrogenation.

KW - asymmetric catalysis

KW - heterocycles

KW - isomerization

KW - phosphorus

KW - stereoselective synthesis

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