Trimethylenemethane cyclization - University Of .-Trimethylenemethane cyclization OO Ph ... CH 2

  • View
    216

  • Download
    0

Embed Size (px)

Text of Trimethylenemethane cyclization - University Of .-Trimethylenemethane cyclization OO Ph ... CH 2

  • M.C. White, Chem 153 -allyl chemistry -375- Week of December 9, 2002

    -Trimethylenemethane cyclization

    O O

    Ph

    SiMe3AcO

    (Ph3P)4Pd

    O O

    Ph

    H

    H

    Provide a mechanism for the following transformation.

    mixture of stereoisomers

    +toluene,

    LnPd(0)Ph

    AcO

    SiMe3 Ph SiMe3OAc Ph

    LnPd(II)

    LnPd(II)

    O O

    Ph

    Pd(II)Ln

    O O

    Ph

    Pd(II)Ln

    O O

    Ph

    H

    H

    Pd(0)Ln

    O O

    Ph

    H

    H

    Pd(0)

    H

    Trost JACS 1980 (102) 6359, JACS 1983 (105) 2326.

  • M.C. White, Chem 153 Metal alkylidenes -376- Week of December 9, 2002

    Metal Carbenes

    singletcarbene

    M CX

    sp2

    pz

    R'

    R

    O C LnM=CR2

    +-

    Fischer Carbenes (formally derived from a singlet carbene)

    (CO)5Cr0

    OMe

    Ph OR

    (CO)5CrII

    PhOMe

    OR

    (CO)5CrII

    Ph OMe

    OR

    COPh

    OMeRO

    Cr0(CO)6

    Fischer Chem. Ber. 1972 (105) 3966.

    Low oxidation state, late metals -acceptor ligands on the metal -donar substituents on the carbene C

    +-

    +

    electrophilic carbenes -donation is stronger than -backbonding resulting in a partial positive charge on thecarbene carbon

    note: that the formal charge for the carbene unit is zero, the #of electrons donated is 2.

    -donation from the carbene substituents competes w/-donation from the metal

    The presence of strong-acceptor ligands on themetal renders -backbonding into the empty carbene porbital weak.

    R'

    X = heteroatoms

    likened to a carbonyl:O

    OMe

    Me

    +-

    18 e-

    triplet carbene

    Schrock Carbenes (formally derived from a triplet carbene)

    M CR

    sp2

    pz

    R

    The metal-carbon bonds are morecovalent in nature and highly polarizedtowards C resulting in a partial negative charge on the carbene C.

    alkyl (or H)

    XR'

    R'

    LnM=CR2

    -+

    High oxidation state, early metals Non- acceptor ligands on the metal (often -donor ligands such as Cp or Cl) alkyl (or H) substituents on the carbene.

    nucleophilic carbenes

    The first characterized Schrock carbene:

    TaV

    t-Bu

    t-Bu

    t-Bu

    t-Bu

    -+

    +

    likened to a phosphorus ylide:Ph3P

    t-Bu

    -+

    O

    pentane/N2

    O2 and moisture sensitive

    -2 charge/4 electron donor

    10 e-

    (t-BuCH2)3TaV

    t-Bu

    O

    (t-BuCH2)3TaV

    O

    t-Bu

    highly oxophilic,early metal

    (t-BuCH2)3TaV O

    t-Bu

    +

    85%

    Schrock JACS 1974 (96) 6796, 1976 (98) 5399.

    M CR

    sp2

    pz

    R

    alkyl (or H)

    XR'

    R'

    extreme -backbonding: where the 2e- in theM(d) orbital aretransfered to the C(pz)orbital.

  • M.C. White, Chem 153 Metal alkylidenes -377- Week of December 9, 2002

    The first isolated and characterizedSchrock carbenes

    The first isolated Schrock carbene:

    TaV

    Me

    MeMe

    18 e-

    C(Ph)3 BF4

    MeC(Ph)3

    TaV

    Me

    CH2

    16 e-

    BF4H

    base TaV

    Me

    CH2

    18 e-

    Schrock JACS 1975 (97) 6577, 6579.

    2.026

    2.246

    ~ 10 % shorter Ta-C bondis suggestive of a significant amount of db character

    The first characterized Schrock carbene:

    (t-BuCH2)2(Cl)TaV t-Bu

    Cl

    H

    10 e- complex

    -agostic interactionprovides the metalw/extra electron density

    2 eq t-BuCH2Li (t-BuCH2)2(Cl)TaV t-Bu

    H

    t-Bu

    steric conjestion induces direct -proton abstraction by one of the neopentane ligands resulting in the metal alkylidene.

    (t-BuCH2)2TaV

    t-Bu

    ClCMe4

    (t-BuCH2)3TaV

    t-Bu

    LiCl LiCl

    Schrock JACS 1974 (96) 6796, Acc. Chem. Res. 1979 (12) 98.

  • M.C. White, Chem 153 Metal alkylidenes -378- Week of December 9, 2002

    Carbonyl methylenation: Tebbes reagent

    TiIV

    Cl

    Cl

    16 e-

    + 2 AlMe3toluene

    rt

    TiIV

    Cl

    16 e-

    AlMe2

    CH4, AlMe2Cl

    Tebbe's reagent: Tebbe JACS 1978 (100) 3611.

    Tebbe's reagent 0.5M soln 100 mL/$363

    (Aldrich 2001) TiIV

    ClAlMe2 Ti

    IV

    O

    TiIV

    OR

    R

    CH2

    16 e-

    TiIV

    ClAlMe2

    stoichiometric

    toluene, -15 oC

    65%

    Synthetic applications:

    EtO2C

    O

    OTBS

    OTBS

    OBn

    OBn

    OTBS

    OTBSCp2TiCH2ClAlMe2

    tol-THF-Py,

    -78oC to -15oC

    82%

    EtO2C

    OTBS

    OTBS

    OBn

    OBn

    OTBS

    OTBS

    key intermediate in the total synthesisof Hikizimycin

    Schreiber JACS 1990 (112) 9657.

    OR

    O

    O

    O Cp2TiCH2ClAlMe2THF, rt, 1h

    85%

    ORO

    O

    Nicolaou ACIEE 1994 (33), 2184, 2187, 2190

    key intermediate in the total synthesisof Zaragozic acid

    In situ prep: Grubbs JOC 1985 (50) 2386.

  • M.C. White, Chem 153 Metal alkylidenes -379- Week of December 9, 2002

    Tebbes reagent

    TiIV

    ClAlMe2 Ti

    IV

    16 e-

    +

    AlClMe2

    TiIV

    TiIV

    Tebbe's reagent reacts with olefins to give metallocyclobutanes:

    Titanium metallocyclobutane 1 reacts with acid chlorides to form Ti enolates.

    1

    Grubbs OM 1982 (1) 1658.

    O

    ClPh

    tol, -20oC to 0oC

    OTiClCp2

    PhPhCHO

    O

    Ph

    OH

    Ph69%

    TiIV TiIV O

    ClPh

    OCl

    Ph

    Grubbs JACS 1983 (105) 1665.

  • M.C. White, Chem 153 Metal alkylidenes -380- Week of December 9, 2002

    Olefin metathesis: Tebbes reagent

    TiIV

    ClAlMe2 Ti

    IV

    16 e-

    +

    t-Bu

    AlClMe2

    TiIV

    t-Bu

    Tebbe's reagent reacts with olefins to give titanacyclobutanes:

    1

    D

    D D

    t-Bu t-Bu

    TiIV

    t-Bu

    D

    t-Bu t-BuD

    D

    TiIV

    D

    D D

    t-But-Bu

    TiIV

    D

    DD

    t-Bu

    TiIV

    t-Bu

    D

    DD

    TiIV

    t-Bu

    DD

    TiIV

    t-Bu

    DD

    t-Bu

    t-Bu

    D

    t-Bu

    t-Bu

    t-BuD

    D

    +1, cat

    +

    Titanacyclobutanes are effective catalysts for -olefin metathesis .

    Grubbs JACS 1982 (104) 7491.

    O

    t-BuO

    O

    t-BuO

    TiCp2

    O

    t-BuO

    TiCp2

    t-BuO

    HO OH

    O

    O

    H H

    H

    Cp2TiCH2ClAlMe2

    DMAP, benzene

    25oC

    90oC

    p-TsOH

    81% overallyield

    Cp2Ti(O)

    ()-Capnellene

    First application of olefin metathesis to synthesis:

    Grubbs JACS 1986 (108) 855.

  • M.C. White, Chem 153 Metal alkylidenes -381- Week of December 9, 2002

    Carbonyl methylenation: Petasis reagent

    OO

    H

    H3C

    Me

    O O

    H3C O

    OH3C OH3C

    OTiCp2CD3

    H3C CD3

    H

    H3C

    Me

    O

    D3C

    OH3C

    H3C

    OH3C

    D

    D

    O

    OCH3

    O

    OCH3

    O

    8 8 62 %

    83 %

    aldehydes ketones

    esters chemoselectivity for ketones in the presence of esters

    80 % 60 %

    Cp2TiMe 23 eq.

    toluene

    60-65 oC

    Cp2TiMe 23 eq.

    toluene

    60-65 oC

    Cp2TiMe 23 eq.

    toluene

    60-65 oC

    Cp2TiMe 21 eq.

    toluene

    60-65 oC

    Based on deuterium labelling studies, Petasis originally proposed a mechanism involving initial carbonyl complexation to Cp2TiMe2 followed by methyl transfer and subsequent loss of methane and titanocene oxide.

    Petasis JACS 1990 112 6392.

    Difficulties with the Tebbe and Grubbs' Ti-mediated olefinations include the high cost of Ti reagent, long preparation times, short shelf life, and the need for specialtechniques due to sensitivity to air and water. Many of these difficulties are overcome with Petasis' procedure which uses dimethyltitanocene. Petasis JACS 1990 112 6392.

    11

    Cp2Ti(CD3)2

    11 ?11

    11

    ~50%

    "significant amount of deuterium detected at C-3."

    H313C O

    OH3CO

    TiCp2

    H313C

    EtO

    H313C

    OH3C

  • M.C. White, Chem 153 Metal alkylidenes -382- Week of December 9, 2002

    Olefin metathesisThe first reports of olefin cross metathesis (heterogeneous cat) by Banks:

    2 Mo(CO)6 supported on Al

    150oC, 30 atm.+

    Banks Ind. and Eng. Chem. (Product Res. and Development) 1964 (3) 170.Haines Chem. Soc. Rev. 1975 (4) 155.

    The first report of ROMP (ring opening metathesis polymerzation):

    MXn + Al(Et)3

    nMXn = TiCl4,ZrCl4, MoCl5, WCl6

    Natta Makromol. Chem. 1963 (69) 163.Natta ACIEE 1964 (3) 723.

    Well-defined WVI and MoVI olefin cross metathesis and ROMP catalysts:

    WVI

    N

    t-BuO

    O

    F3C

    H3C

    F3C

    F3CF3C

    CH3

    i-Pr i-Pr

    MoVI

    N

    t-BuO

    O

    F3CH3C

    F3C

    F3CF3C

    CH3

    i-Pr i-Pr

    Wittig-type chemistry with aldehydes>ketones>> and esters(slow rates).

    Wittig-type chemistrywith aldehydes>>ketones (slow rates).

    Schrock JACS 1986 (108) 2771.Schrock JACS 1990 (112) 3875, 8378;1991 (113) 6899.

    Olefin cross metathesis:

    Mn

    t-Bu

    12 e- 12 e-

    Mn

    t