CHEM 220B: Organic Chemistry - Carbon-Carbon Bond-Forming Reactions

Carbon-Carbon Bond-Forming Reactions in Organic Synthesis

Cross-Coupling Reactions

  • Recognize and understand various cross-coupling reactions:
    • Organocuprate
    • Suzuki
    • Heck
    • Stille
    • Sonogashira
  • Predict the molecular outcome of reactions involving carbenes.
  • Predict the outcomes of ring-closing olefin metathesis reactions.

Organocuprates (24.1)

  • Organocuprate is a weaker base than RMgX and RLi.
    • Good for substitution reaction of 1° RX.
    • Not an SN2 reaction, proceeds via oxidative addition and reductive elimination.

Three Fundamental Mechanisms

  • Oxidative addition
  • Reductive elimination
  • Migratory insertion
  • Organocuprate reactions are based on oxidative addition and reductive elimination.

Cross-Coupling Reactions by Palladium Complexes

A. Suzuki Reaction (24.2)
  • The Pd-catalyzed coupling of an alkenyl or aryl borate with an alkenyl or aryl halide.
B. Heck Reaction (24.3)
  • The Pd-catalyzed coupling of an alkene with an alkenyl or aryl halide.
  • R−XR-X + Alkene --(Pd catalyst, base)--> Substituted alkene
  • R−XR-X: Organohalide (X=I,Br,OTf,ClX = I, Br, OTf, Cl)
  • Alkene: Less hindered
  • Base: Et3NEt_3N
  • Substituted alkene: Z=H,R,Ar,CN,CO<em>2R,OAc,NHAc,NO</em>2Z = H, R, Ar, CN, CO<em>2R, OAc, NHAc, NO</em>2
  • Reaction Pathway:
    1. Oxidative addition
    2. Migratory insertion (less hindered)
    3. beta-Hydride elimination
    4. Pd-catalyst regeneration
C. Stille Coupling Reaction (24.4)
  • The Pd-catalyzed coupling of an alkenyl or aryl tin reactants with an alkenyl or aryl halide.

Carbenes (24.5)

  • Addition of carbene to C=C bond.
  • Dihalocarbenes
  • Methylene (:CH2) is prepared by the decomposition of diazomethane.
  • The Simmons-Smith carbenoid

Olefin Metathesis (24.7)

  • The metal-alkylidene-catalyzed reaction of two alkenes switching groups.

  • Catalysts:

    • Grubbs catalyst:
      • Structure includes Ruthenium (Ru) center.
      • Ligands: P(Cy)3P(Cy)_3, Cl, and a Ph group.
    • Schrock catalyst:
      • Structure includes Molybdenum (Mo) center.
      • Ligands: O, and F3CF_3C.

  • Types of Olefin Metathesis:

    • ROMP (Ring-Opening Metathesis Polymerization)

    • RCM (Ring-Closing Metathesis)

    • CM (Cross Metathesis)

    • Ethenolysis

    • RCM

    *Catalyst is either Ru or Mo.