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

    Fingerprint

    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

    Hintermann, Lukas ; Schmitz, Marco ; Maltsev, Olegv ; Naumov, Pance. / Organocatalytic stereoisomerization versus alkene isomerization : Catalytic asymmetric synthesis of 1-hydroxy-trans -2,5-diphenylphospholane 1-oxide. In: Synthesis (Germany). 2013 ; Vol. 45, No. 3. pp. 308-325.
    @article{5efd3eddb22f4eda95b4e3f4a09429d9,
    title = "Organocatalytic stereoisomerization versus alkene isomerization: Catalytic asymmetric synthesis of 1-hydroxy-trans -2,5-diphenylphospholane 1-oxide",
    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.",
    keywords = "asymmetric catalysis, heterocycles, isomerization, phosphorus, stereoselective synthesis",
    author = "Lukas Hintermann and Marco Schmitz and Olegv Maltsev and Pance Naumov",
    year = "2013",
    month = "1",
    day = "11",
    doi = "10.1055/s-0032-1316835",
    language = "English (US)",
    volume = "45",
    pages = "308--325",
    journal = "Synthesis",
    issn = "0039-7881",
    publisher = "Georg Thieme Verlag",
    number = "3",

    }

    TY - JOUR

    T1 - Organocatalytic stereoisomerization versus alkene isomerization

    T2 - Catalytic asymmetric synthesis of 1-hydroxy-trans -2,5-diphenylphospholane 1-oxide

    AU - Hintermann, Lukas

    AU - Schmitz, Marco

    AU - Maltsev, Olegv

    AU - Naumov, Pance

    PY - 2013/1/11

    Y1 - 2013/1/11

    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

    UR - http://www.scopus.com/inward/record.url?scp=84872972940&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=84872972940&partnerID=8YFLogxK

    U2 - 10.1055/s-0032-1316835

    DO - 10.1055/s-0032-1316835

    M3 - Article

    VL - 45

    SP - 308

    EP - 325

    JO - Synthesis

    JF - Synthesis

    SN - 0039-7881

    IS - 3

    M1 - SS-2012-T0745-FA

    ER -