Dcc Coupling

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DCC-coupling

Transcript of Dcc Coupling

  • DCC Coupling

    Dicyclohexylcarbodiimide (DCC)

    N C N

    O

    OH

    N Ncat.OH,

    O

    O

    N,N-dimethylaminopyridine (DMAP)

    OH

    ODCC , 2-butanol , DMAP

    OH

    ODCC , BuNH2 , DMAP

    O

    O

    N

    O

    H

  • DCC Mechanism

    N C N

    H O

    O

    N C N

    H O

    O

    O

    H

    Et

    H

    O CHMe2

    Me2HCMe2HC

    N C N N C N

    O

    O

    H

    H

    O

    O

    !+ !+

    CHMe2

    Me2HC

    C

    O

    N

    H

    N

    H

    O

    O CHMe2

    +Me2HC

    Dicyclohexyl ureaH2N

    O

    NH2

    UreaDCC used for coupling amino acids to form peptides

  • DCC Coupling

    OH

    OPhPh

    C6H13

    N

    Et

    H

    DCC

    N

    OPhPh

    C6H13

    Et

    DCC coupling to couple amino acids to make peptides

    H2N CO2Et

    HN COOH

    MeH

    Ph H

    O

    O

    +DCC

    N

    MeH

    H

    O

    O

    O

    N CO2Et

    H

    Ph

    H

    Ethyl ester of phenylalaninetert-butyl carbamate (Boc) of alanine

    Boc

    A protected dipeptide, phe-ala

  • Imides

    O

    O O NH3

    OH

    O

    H2N

    O

    Via acyl substitution

    Cl

    O

    HN

    O O

    H2N

    O

    H2N

    O

    +LiHN

    OBuLi

    Cl

    O

    NH

    O O

  • Cyclic Anhydrides

    CO2H

    CO2H 200C

    H2O

    O

    O

    O

    CO2H

    CO2H 200C

    H2O

    O

    O

    O

    CO2H

    CO2H 200C

    H2O

    O

    O

    O

    Succinic anhydride

    Glutaric anhydride

    Phthalic Anhydride

  • Cyclic Imides

    O

    O

    O

    NH3

    N

    O

    O

    H

    O

    O

    O

    MeNH2

    N

    O

    O

    Me

    O

    O

    O

    PhNH2

    N

    O

    O

    Ph

    succinimide

    N-methylglutarimide

    N-phenylphthalimide

  • Lactams and Lactones

    NN

    N

    H

    O

    H

    O

    H O

    a !-lactam

    N

    S

    O

    CO2H

    Me

    Me

    HHN

    HO

    H2N

    HOamoxicillin (a penicillin)

    OO

    O

    O O O

    O

    O

    O

    Me

    HO

    Me

    Me

    Me

    O OHO

    H

    Me

    Me2N

    methymycin ( a macrocyclic lactone)

  • Acyl Substitution With Carbon Nucleophiles

    Grignard reagents

    1. 2 equiv. MeMgI 2. H3O+

    CO2Et

    OH

    Me

    Me 88%

    O

    Me

    MeMgI MeMgI

    and then hydrolysis

    C7H15

    O

    Cl

    C7H15

    O

    Cl

    Bu

    BuMgBr

    C7H15

    O

    Bu

    - Cl

    C7H15

    O

    Bu

    Bu

    BuMgBr

    C7H15

    OH

    Bu

    Bu

    H3O+

  • Other Acid Derivatives

    CO2Et1. 2 PhMgBr , THF

    2. H3O+

    Ph

    Ph

    OH

    OH

    1. PBr32. Mg , THF

    3. PhCO2Me

    4. H3O+

    Ph

    OH

    OH

    PBr3Br

    Mg

    etherMgBr

    1. PhCO2Me

    2. H3O+

    Ph

    OH

    OH

    1. CrO3 , aq H+

    acetone , heat

    2. SO Cl2

    3. EtMgCl , ether

    4. H3O+

    OH

    EtEt

    OH CrO3 , aq H+

    acetone , heat

    OH

    O

    SOCl2Cl

    O

    EtMgCl

    ether

    OH

    EtEt

  • Dialkylcadmium Reagents

    2 RLi + CdCl2 R2Cd + 2 LiCl

    A dialkyl cadmiumMe2Cd dimethylcadmiumBu2Cd dibutylcadmium

    Me Cl

    O

    1.

    2. H3O+

    Et-MgX +2

    Et2Cd

    CdCl2 Et2Cd

    Also with Grignard reagents

    React with acid chlorides to give ketones

    Me

    O

    Cl

    OLi

    1. 0.5 CdCl2

    2.

    O

  • Other Carbon-Carbon Forming Reactions

    Et

    Et

    O

    O

    Br

    1. NaCN , DMF

    2. H3O+ , heat

    3. 2-propanol , cat. H+

    O

    O

    New C-C bond

    CN

    O

    OH

    Cl

    O

    Ph2CuLi , ether

    Cl

    O

    Bu2CuLi , ether

    10C

    Ph

    O

    O

    Friedel-Crafts

    organocuprates

    Cyanide SN2

    OH

    O1. SOCl2

    2. ethylbenzene

    AlCl3

  • Reduction

    Cl

    O 1. LiAlH4 , ether

    2. H3O+ OH

    H2 , Pd-C

    EtOH

    OH

    O

    O O

    1. LiAlH4 , ether

    2. H3O+

    OH HO

    CO2Et

    1. LiAlH4 , ether

    2. H3O+ OH

    + EtOH

    NH2

    O1. LiAlH4 , ether

    2. H3O+ NH2

    CN

    1. LiAlH4 , ether

    2. H3O+

    CH2NH2

    NH2

    H2 , Pd-C

    EtOH

    NH2

  • Dibal

    H+ EtOH

    O

    Al

    HDiisobutylaluminum hydrideDibal orDibal-H

    Milder reducing agent Converts esters to aldehydes at low temperature

    CO2Et

    1. Dibal , THF , 78C

    2. H3O+

  • Spectroscopy

    IR: acid chloride C=O, 1810 (PhCOCl , 1770) anhydride 1820 + 1760 ester 1770 amide 1690 + 1650

    NMR: a C=O 2.1 - 2.6 CO2H >12 (exchange with D2O)

    NH2 1-6 (slow exchange with D2O) O=C-OCH 3.5-4.0

  • Acid chloride , 1806 Acid anhydride , 1832 , 1761

    Methyl acetate , 1748

    acetamide , 1681

    acetamide , 1655 + 1653

    1700Methyl acrylate , 1732

    IR

  • Chapter 22. Enols and Enolate Anions

    C

    OH

    C

    O

    Keto-enol tautomerismenol

    C

    OH

    X C

    O

    X

    H

    :Base

    C

    O

    C

    O

    C=C of an enol can react with an electrophile

    An enol can react with a base to form a resonance stabilized enolate anion