pd - ccc/upcmldccc.chem.pitt.edu/wipf/current literature/jaehyeon_1.pdforganic synthesis using...
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Pd•A versatile catalyst for carbon-carbon bond formation.
•Tolerant to many functional groups such as carbonyl andhydroxyl groups.
•NOT “VERY” sensitive to oxygen.
•Not toxic
BUT
•Expensive (less expensive than Rd, Pt and Os)
Palladium reagents and catalysts, Jiro Tsuji, Wiley
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Two kinds of Pd compounds useful for organic synthesis:
Pd(II): such as PdCl2 Pd(acac)2 and Pd(OAc)2
•Used either stoichiometric rgts or catalysts
•Stable
•Used as unique stoichiometric oxidizing agents and s precursors of Pd(0)compelxes
Pd(0): reduced from Pd(II)•Used as catalysts
•Usually prepared from Pd(OAc)2 with phosphine ligands.
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Examples of organic reactions using Pd(0)
Coupling reactionL2Pd(0)
RX
Oxidative addition
L2Pd(II)R
X
Transmetallation
R'MMX
L2Pd(II)R
R'
R R'
Reductive elimination
When M isSn : Stille reactionB : Suzuki reactionCu : Sonogashira reactionZn : Negishi reaction
Organic Synthesis using Transition metals, Rod Bates, Sheffield academic press
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Alkene insertion reaction
Heck reaction
Ar-X +OMe
O
OMe
O
ArPd(OAc)2
PPh3Base
L2Pd(0)RX
Oxidative addition
L2Pd(II)R
X
PdR
X
L
R'R'
PdR
X
LInsertion
R'R
PdLX
L2Pd(II)HX
Base
Base·HX
R'R
b-hydride elimination
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Heck reaction
•Typically needs 1-5 mol % Pd catalyst along with Phosphine ligand and base
•Maximum turnover numbers (TON): only 20-100
•Not practical for large-scale industrial application
Challenge
New Heck reaction catalyst
•with higher TON•and enhanced reactivity with deactivated aryl bromides or aryl chloride
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Precedents of Ligand-free Heck reaction
In Phase-transfer condition
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Precedents of Ligand-free Heck reaction
They did not explain why.
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Precedents of Ligand-free Heck reaction
In ionic liquid
Majorly, to recycle palladium catalystOf course, phosphine ligand accelerated the reaction significantly.
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Precedents of Ligand-free Heck reaction
Waste-free Heck reactions
Halogen free condition
Oxygen oxidized Pd(0) to active Pd(II)
Water is the only by-product
Various additives were tested
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Possbility of Pd(OAc)2 as an active catalyst without Phosphine ligands
Base Selection : K3PO4 showed the best result
Ligand-free Heck reaction
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Solvent optimization
DMA=N,N-dimethylacetamide
DMA showed the best result.
O
N
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Generality of this reaction
Showed very high yield and TON in various combinations.
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Interesting point:
•Activated terminal olefin such as n-butyl arylate gove low yields except for thecoupling with the more active 4-bromobenzaldehyde. -> New mechanism?!
•Cyclic olefins such as norbornene and 2,4-dihydropyran did not react.
•Triflate and chloride were completely ineffective in this system.
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Comparison with other catalyst systems
Similar or better than the other catalytic systems.
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Proposed mechanism: without Pd(0) species
Intermediate I was assumed because there’s no predents of direct oxidative addtion of Ar-X to Pd(OAc)2
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Summary
Pd(OAc)2, in combination with K3PO4 as the base and DMA as the solvent,can be used as a highly reactive catalyst for the Heck reaction.
Activated and deactivated aryl bromides can be used in the absence of anystabilizing ligands or special additives.
Cheap reaction! (cheap catalyst, cheap base and ligand-free)
Limitation
Beneficial to only aryl bromides and unactivated terminal olefinsNeeds long reaction timeNeeds high temperature