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Similar to Heck cross coupling reaction
Heck cross coupling reaction
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- 2. HECK REACTION Dr. ShahidRasool Heck reaction CHEM5128 Advanced Named Reactions 2
- 3. Key Concepts • Introductionto Heck reaction • Discussion of reacting species, catalysts, solvents • Mechanism of reaction • Explanation of mechanism step by step • Synthetic applications 3
- 4. Heck Reaction: • Heckreaction is also known as Mizoroki-Heck reaction. • Palladium catalyzed coupling of organohalides or triflates with olefins in the presence of a base • C-C bond is generated between halogen bearing group and the sp2- hybridized carbon of olefin • A way to substitute olefin • Overall reaction,
- 5. History: • Fujiwara (1967)- Coupling of arenes (Ar–H) & alkenes by Pd(II) • Heck (1969) – Coupling of Arylmercuric halides (ArHgCl) & alkenes by Pd(II) • Mizoroki (1971) - coupling of iodobenzene & styrene
- 6. History: • Heck (1972)- introduced Palladium acetate and tertiary amine • Heck (1974) - introduced phosphine ligands
- 7. Alkyl halides orTriflates (R-X): • R = Benzyl, Vinyl, Aryl groups • X = Cl, Br, I or Otf • No Heck reaction with alkyl halide because OTf = F3C S O O O
- 8. Olefins: • Olefin musthave one sp2-C-H bond • EWG activate reaction • Acrylates are the most favorable • Difference between terminal alkene and cyclic alkene CH2 CH C Acrylate group O O R
- 9. Catalysts and bases: •Catalyzed by palladium salts and complexes Typical catalysts are • Tetrakis(triphenylphosphine)palladium(0) - Pd(PPh3)4 • Palladium chloride - PdCl2 • Palladium (II) acetate – Pd(OAc)2 Typical ligands are • Triphenylphosphine (PPh3) • Phosphinooxazolines (PHOX) • 2,2′-Bis(diphenylphosphino)-1,1′-binaphthyl (BINAP) Typical bases are • Triethylamine (NEt3) • Potassium carbonate (K2CO3) • Sodium acetate (CH3COONa) PHOX BINAP
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- 11. Step-1, Oxidative addition: •This step is known to follow concerted mechanism of addition. • Pd(0) is oxidized to Pd(II) • R-X is added in concerted way • Both ‘R’ and ‘X’ are attached to ‘Pd’ through its primary valency. • Secondary valency ‘4’ is already justified by bidendate ligands. Pd L X L2Pd(0) R X L2Pd(0) R X R LII
- 12. Step-2, Coordination: • π-electronsof olefin are coordinated to Palladium metal • Two types of coordination are possible, • (1) π-donation from HOMO of alkene to empty orbital of Pd • (2) σ-donation from filled orbital of metal to LUMO of alkene Pd L X R LII CHH2C Pd L X R LII CHH2C
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- 14. Step-3, Insertion andinternal rotation: • Insertion follows the formation of bonds between one carbon of olefin to metal and other carbon of olefin to already attached vinyl, benzyl or aryl group of alkyl halide • It follows syn addition. • Internal rotation happens because bulky groups move to trans. Pd R L L XII CHH2C CHH2C Pd L L XII R
- 15. Step-4, β-hydride elimination: •Reaction involving conversion of alkyl group bonded to a metal centre into metal-bonded hydride and an alkene • Alkyl group must have hydrogen on β-carbon • Metal complex must have an empty (or vacant) site cis to alkyl group CHC Pd L L XII R H H CHC R H H Pd L L XII
- 16. Step-5, Reductive elimination: •π-Complex is destroyed and product is obtained • Catalyst is regenerated through the reaction with base • Pd(II) is reduced to Pd(0) • ‘Hydrogen’ and ‘Halogen’ atoms are removed from the complex CHC R H H Pd L L XII CHC R H H Pd L L XII H Pd L L XII NEt3 Pd LL 0 Et3NH X
- 17. Stereo-selectivity: • Stereoselective withtendency for trans product as palladium halide group and bulky organic residue move away from each other in the reaction sequence in a rotation step.
- 18. Synthesis of Naproxen(non-steroidal anti-inflammatory drug, NSAID): Synthesis of Octyl methoxycinnamate (Sunscreens): O Br O O Pd(0) O O O Heck Oxyarylation:
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