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    Total Synthesis of ( ) - Sinulariadiolide. A Transannular Approach

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    Chem Mistry
    1) The starting material is (R)-(–)-carvone, which is commercially prepared from isoprenol via oxidation with methylsulfonyl oxide followed by ozonolysis and reduction with triphenylphosphine. 2) The organocatalyst used is Z, which can be prepared from commercially available isoprenol. 3) A transannular approach was used to synthesize (-)-sinulariadiolide involving functionalization of two hydroxyl groups followed by ring contraction to form the lactone ring.

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    Total Synthesis of ( ) - Sinulariadiolide. A Transannular Approach

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    Chem Mistry
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    1) The starting material is (R)-(–)-carvone, which is commercially prepared from isoprenol via oxidation with methylsulfonyl oxide followed by ozonolysis and reduction with triphenylphosphine. 2) The organocatalyst used is Z, which can be prepared from commercially available isoprenol. 3) A transannular approach was used to synthesize (-)-sinulariadiolide involving functionalization of two hydroxyl groups followed by ring contraction to form the lactone ring.

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    5ec2bb39beccc551387a4c9e_20200518_(−)-Sinulariadiolide_p

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    1) The starting material is (R)-(–)-carvone, which is commercially prepared from isoprenol via oxidation with methylsulfonyl oxide followed by ozonolysis and reduction with triphenylphosphine. 2) The organocatalyst used is Z, which can be prepared from commercially available isoprenol. 3) A transannular approach was used to synthesize (-)-sinulariadiolide involving functionalization of two hydroxyl groups followed by ring contraction to form the lactone ring.

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    32 views2 pages

    Total Synthesis of ( ) - Sinulariadiolide. A Transannular Approach

    Uploaded by

    Chem Mistry
    1) The starting material is (R)-(–)-carvone, which is commercially prepared from isoprenol via oxidation with methylsulfonyl oxide followed by ozonolysis and reduction with triphenylphosphine. 2) The organocatalyst used is Z, which can be prepared from commercially available isoprenol. 3) A transannular approach was used to synthesize (-)-sinulariadiolide involving functionalization of two hydroxyl groups followed by ring contraction to form the lactone ring.

    Copyright:

    © All Rights Reserved
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    of 2

    Total Synthesis of (−)-Sinulariadiolide.

    A Transannular Approach
    Zhanchao Meng and Alois Fürstner; J. Am. Chem. Soc. 2019, 141, 805–809.

    1) Name the starting material. How is this commercially


    O prepared from isoprenol?
    1) Me2SO4, i-Pr2NEt, 0 °C
    HO
    then O3, −78 °C, then PPh3
    2) Z (25 mol%), CuCl2 (12 mol%),
    2) Name of the organocatalyst Z? How would you
    TEMPO, MS 4 Å, −10 °C (e.r. 83%)
    prepare it?
    1-6 3) propyn-1-ylmagnesium bromide, pentane
    4) TBSCl, imidazole
    5) B2(pin)2, t-BuONa (15 mol%), CuCl (6 mol%),
    (S,S)-methyl-DUPHOS (6 mol%), MeOH/THF
    6) NaBO3·6H2O, aq. THF, 90 °C
    Me
    O P
    N
    Me
    Me
    A N P
    Ph H2 BF –
    4
    Me
    Z
    (S,S)-methyl-DUPHOS
    (R)-(–)-carvone
    7) aq. H2O2, NaOH
    8) TsNHNH2, HOAc, CH2Cl2 8) Hint: a fragmentation occurs
    7-10
    9) NaClO2, NaH2PO4, 2-methylbut-2-ene, t-BuOH/H2O
    10) Y, DCC, DMAP, Et3N, CH2Cl2, then A, PhMe, 60 °C

    O
    Me O OH
    O pKa? MeOOC
    Ph O
    O O OH

    Y H O H
    H
    O
    B (−)-sinulariadiolide
    11) Ac2O, DMAP (20 mol%), Et3N, CH2Cl2, −40 °C; 11) Hint: 1,3-dicarbonyl compounds are not well-
    12) aq. HF, THF tolerated by the molybdenum alkylidynes/silanolate
    13) X (30 mol%), PhSi[CH2CH2(Ph)2SiOH]3 (30 mol%) catalyst-ligand systems
    11-15
    toluene, 120 °C
    14) Zn, HOAc, THF/H2O
    15) Bu3SnH, [Cp*RuCl]4 (11 mol%) 15) Mechanism?

    Mo N
    N
    N t-Bu

    C X

    16) CO (1 atm), Pd(OAc)2 (20 mol%), AsPh3 (40 mol%)


    1,4-benzoquinone, TFA (40 mol%), MeOH 17) Hint: numerous attempts to induce ring contraction at
    16-19 17) triphosgene, CH2Cl2, pyridine, 0 °C this stage failed, hence two hydroxyl groups were
    18) Cs2CO3, CH2Cl2, MeOH/H2O functionalized first.
    19) BBr3, 2-methyl-2-butene, CH2Cl2

    Me O OH
    MeOOC
    O
    OH

    H O H
    H
    O
    (−)-sinulariadiolide

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