Synthetic uses of transition metals, GCLJ
editTextbooks
edit- Clayden, Chapter 48 (Organometallic chemistry), pp. 1311–1343
Introduction
edit- 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
- R-Pd-X species are not [R−][+PdX]
- Transmetallation
- Tris(dibenzylideneacetone)dipalladium(0), Pd2(dba)3
Pd-catalyzed coupling reactions
editStille
editSuzuki
edit- Suzuki coupling
- use catecholborane to form vinylborane precursor
- use Pd(PPh3)2Cl2 to catalyse addition of RX (organohalide, e.g. PhBr)
Negishi
editKumada
editSonogashira
editUse of Sonogashira coupling in enediyne synthesis
edit- 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
edit- "Amination", R-X → R-NH-R′
- RX + R′NH2 → RNHR′ + HX
- Catalysed by 0PdL2
- [R′H2N+PdL2R][X−] deprotonated
sp³ hybridised carbon in the oxidative addition process
editHeck reaction
edit- Heck reaction
- Named after Richard Heck who developed the reaction in the 1970s
Mechanism
edit- 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)
editCyclopropanation using electrophilic carbene complexes
edit- 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
edit- Example of a Cu-catalysed asymmetric cyclopropanation: synthesis of cilastatin
Ring-closing metathesis
edit- Ring-closing metathesis
- catalysed by Grubbs' first generation catalyst, Cl2(Cy3P)Ru=CHPh