User:Benjah-bmm27/degree/3/GCLJ2

Synthetic uses of transition metals, GCLJ

Textbooks

• Clayden, Chapter 48 (Organometallic chemistry), pp. 1311–1343

Introduction

• Organopalladium chemistry
  • R-Pd-X species are not [R⁻][⁺PdX]
    • no carbanionic character
    • not basic or nucleophilic
    • react with nucleophiles (pi donors, R′-M)
    • Pd(II) slightly electrophilic
• Transmetallation
• Tris(dibenzylideneacetone)dipalladium(0), Pd₂(dba)₃

Pd-catalyzed coupling reactions

• Palladium-catalyzed coupling reactions

Stille

• Stille coupling

Suzuki

• Suzuki coupling
  • use catecholborane to form vinylborane precursor
  • use Pd(PPh₃)₂Cl₂ to catalyse addition of RX (organohalide, e.g. PhBr)

Negishi

• Negishi coupling

Kumada

• Kumada coupling

Sonogashira

• Sonogashira coupling

Use of Sonogashira coupling in enediyne synthesis

• Synthesis of calicheamicin
  • calicheamicin is an enediyne antibiotic and anti-tumour drug: the enediyne "warhead" or "business end" works by doing a Bergman cyclization

Hartwig-Buchwald coupling

• "Amination", R-X → R-NH-R′
• RX + R′NH₂ → RNHR′ + HX
• Catalysed by ⁰PdL₂
• [R′H₂N⁺PdL₂R][X⁻] deprotonated

Heck reaction

• Heck reaction
  • Named after Richard Heck who developed the reaction in the 1970s

Mechanism

• ChemTube3D animated Jmol mechanism
• Surawatanawonga, Fan, Hall (2008) Density functional study of the complete pathway for the Heck reaction with palladium diphosphines
• Surawatanawong, Hall (2008) Theoretical Study of Alternative Pathways for the Heck Reaction through Dipalladium and “Ligand-Free” Palladium Intermediates

Other interactions of alkenes with Pd(II)

• Allylic rearrangements

Cyclopropanation using electrophilic carbene complexes

• Cyclopropanation using electrophilic carbene complexes
  • Carbene complexes are often called carbenoids
  • Cyclopropanes are found in nature as pyrethrins, and are produced synthetically as pyrethroid insecticides
  • Use ethyl diazoacetate as a source of :CEt₂ (or more generally use R₂CN₂ as a source of :CR₂)
  • Use an alkene as a source of R₂C^•—^•CR₂
  • R₂C: + R₂C^•—^•CR₂ → cyclo-(R₂C)₃, i.e. a cyclopropane
  • Cu or Rh catalyst

Cilastatin synthesis

• Example of a Cu-catalysed asymmetric cyclopropanation: synthesis of cilastatin

Ring-closing metathesis

• Ring-closing metathesis
  • catalysed by Grubbs' first generation catalyst, Cl₂(Cy₃P)Ru=CHPh