New progress in palladium catalyzed coupling reactions
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New progress in palladium catalyzed coupling reactions

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New progress in palladium catalyzed coupling reactions

New progress in palladium catalyzed coupling reactions

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New progress in palladium catalyzed coupling reactions New progress in palladium catalyzed coupling reactions Presentation Transcript

  • New Progress in PalladiumCatalyzed Coupling Reactions Yiming Chen May 2nd, 2011
  • New Progress in PalladiumCatalyzed Coupling Reactions• List of Reactions• Mechanism of Catalysis• New Progresses• Summary
  • Palladium Catalyzed Coupling Reactions• Heck Reaction • Stille Reaction• Suzuki Reaction • Hiyama Reaction• Negishi Reaction • Sonogashira Reaction• Fukuyama Reaction• Buchwald–Hartwig Reaction
  • Palladium Catalyzed Coupling Reactions Name Reactant I Reactant II Heck Reaction alkene R-XSogonashira Coupling alkyne R-X Negishi Coupling R-Zn-X R-X Stille Coupling R-SnR3 R-X Suzuki Reaction R-B(OR)2 R-X Hiyama Coupling R-SnR3 R-X Buckward-Hartwig R2-NR SnR3 R-X AminationFukuyama Coupling RCO(SEt) R-Zn-I
  • New Progress in PalladiumCatalyzed Coupling Reactions• List of Reactions• Mechanism of Catalysis• New Progresses• Summary
  • Heck Reaction Pd (0) R R X + R Base R• R-X: X=Br, Cl, OTf; R=Aryl, Vinyl or Benzyl;• Alkene: at least one -H, often electron-deficient;• Metal: PdCl2, Pd(OAc)2, Pd(PPh3)4;• Ligand: PPh3, BINAP;• Base: Et3N, K2CO3, NaOAc;• Trans product. J. Org. Chem., 1972, 37 (14), pp 2320–2322
  • Heck Reaction OCH3 OCH3 Br LO L Br +II Pd O Pd +II L H3CO H L O H H L Br Pd +II H L OCH3 OCH3 Br O Br L L O Pd Pd Br +II +II L L L 0 Pd L
  • Suzuki Reaction Pd catalyst R1-B-Y2 + R2-X R1-R2 Base• Aryl- or Vinylboronic acid with aryl- or vinyl-halide;• Reactivity: R-I > R-OTf > R-Br >> R-Cl• Catalyst: Pd (0), like Pd(PPh ) 3 4 Chem. Rev., 1995, 95 (7), pp 2457–2483
  • Suzuki Reaction R1-R2 Pd (0) R2-X +II R2-Pd-X Y t-BuONa R1 B- Ot-Bu +II Y R1-Pd-R2 +II R2-Pd-Ot-Bu t-BuONa Y R1 B Y
  • Neigishi Coupling MLn R-X + R-Zn-X R-R• Reactant: Organic halide and organozinc compound;• Catalyst: zerovalent palladium or nickle;• Ligand: PPh3, dppe, BINAP, chiraphos;• X=Cl, Br, I, OTf, RCOO; R=alkenyl, aryl, allyl, alkynyl or propargyl;• X’=Cl, Br, I; R’=alkenyl, aryl, allyl or alkyl. Chem. Commun., 1977, 683-684
  • Neigishi Coupling Pd(0) R-R R-X R-Pd-R R-Pd-X +II +II X-Zn-X R-Zn-X
  • Stille Reaction R-SnR3 + R-X R-R + X-SnR3• Reactant: Organotin compound and sp2- hybridized organic halide;• Catalyst: palladium;• Trimethylstannyl or tributylstannyl compounds are used. J. Am. Chem. Soc., 1978, 100 (11), pp 3636–3638
  • Stille Reaction +II PdR1-R2 0 PdLn R1-X +II +II R1-PdLm-R2 R1-PdLm-X XSnBu3 R2SnBu3
  • Buchwald–Hartwig Amination• Reactant: Aryl Halide (X could be OTf) and amine;• R Metal: Palladium X R MLn N R + H-N base• Ligand: wide range of R phosphines;• Could be extended to C or O Nu. J. Am. Chem. Soc., 1994, 116 (17), pp 7901–7902
  • Buchwald–Hartwig Amination L-Pd-L R Pd-L Ar-XAr N R Ar Ar R Ar L Pd X L Pd Pd N X Pd L X L R Ar Ar R R H L Pd N HN R R X
  • Sonogashira Coupling R-X Pd/Cu+ H R R R base• X=Cl, Br, I, OTf; R=Ar, alkenyl;• Catalyst: zerovalent palladium and halide salt of Cu(I);• Cu(I) reacts with terminal alkyne and yields copper(I) acetylide, which is activated species. Tetra. Lett., 1975, 16 (50),pp 4467-4470
  • Sonogashira Coupling R R Ph3P-Pd-PPh3 R-I R PPh3 Ph3P-Pd-Ph3P Ph3P-Pd-R R I Ph3P-Pd-Ph3P R R Cu+ R Cu R H Cu+ R H Cu
  • Hiyama Coupling Pd (cat.) R X + R3Si R R R F- or base• Reactant: aryl, alkenyl, or alkyl halides (or or pseudohalides) and organosilanes;• Requires activation reagent like F- or base; J. Org. Chem., 1988, 53 (4), pp 918–920
  • Hiyama Coupling L2Pd X-R L R R Pd XL Pd R L L R3Si-R L R Pd R L R3Si-X
  • Fukuyama Coupling O O + Zn R2 Pd R1 S I R1 R2 Et• Reactant: thioester and organozinc halide;• Product: ketone;• Reaction will stop at the ketone, won’t produce tertiary alcohol; Tetra. Lett., 1998, 39(20), pp 3189-3192
  • Fukuyama Coupling O O R R’ SEt Pd R SEt O O SEt R R Pd R Pd EtSZnI RZnI
  • Palladium Catalyzed Coupling Reactions1. Pd (0) complexes are prepared in situ from Pd (II);2. Oxidative Addition of Pd (0) complexes;3. Transmetallation or ligand exchange;4. Trans - Cis Isomerization;5. Reductive Elimination.
  • Mechanism Study: Oxidative Addition• The author postulates the mechanism of oxidative addition, theoretical kinetics property agrees with experiment observations. J. Am. Chem. Soc., 2009, 131, 8141– 8154
  • Mechanism Study: Oxidative Addition1. Double-coordinated Pd forms π-complex with aryl halide;2. Ligand L is replaced by aromatic ring;3. σ-complex forms between C-X bond and Pd atom;4. Pd inserts into C-X bond. J. Am. Chem. Soc., 2009, 131, 8141– 8154 Dalton Trans., 2010, 39, 10833-10836
  • Mechanism Study: Oxidative Addition• Another paper shows similar mechanism on allyl bromide. Organometallics, 2006, 25, 3647-3658
  • Mechanism Study:Transmetalation Organometallics, 2006, 25, 3647-3658
  • Mechanism Study: Reductive Elimination• The mechanism depends on ligands and R- groups coordinated with Pd atom. J. Am. Chem. Soc., 2009, 131 (10), pp 3650–3657
  • Mechanism Study: Reductive Elimination1. There is no universal elimination mechanism;2. In most cases, elimination is direct;3. When R= CH3 and L=CH3CN, elimination is stepwise, initiated by dissociation of L. J. Am. Chem. Soc., 2009, 131, 8141– 8154 Dalton Trans., 2010, 39, 10833-10836
  • Palladium Catalyzed Coupling Reactions1. Many Pd (0) complexes are sensitive to air or moisture;2. Long reaction time, high temperature;3. Highly toxic compounds are use as ligands in reaction;4. Activated reactants are required.
  • New Progress in PalladiumCatalyzed Coupling Reactions• List of Reactions• Mechanism of Catalysis• New Progresses • Innovative Catalyst • Improved Reaction Condition • New Reaction Category• Summary
  • Innovative Catalyst (1)• Link ligands to nanoparticles to improve recyclability of catalyst. Could be used to catalyze Heck reaction, Sonogashira reaction as well as cyanation reaction. Tetrahedron, 2007, 63, pp6784–6790
  • Innovative Catalyst (1)The new catalystshows good yieldon these couplingreactions.
  • Innovative Catalyst (II)• Magnetic nanoparticle-supported heterogeneous catalyst for Suzuki, Sonogashira, and Stille Coupling. Angew. Chem., 2010, 122, 1137 –1140
  • Innovative Catalyst (II) (HO)2B Suzuki: 71%-95% 0.5 mol% cat. Cl + K2CO3, TBAB, H2O R1 R1 R2 R2 Sonogashira: 74%-96% 0.5 mol% cat. Cl + R2 R2 piperdine TBAB, H2OR1 R1 Stille: 81%-96% 0.5 mol% cat. Cl + Bu3Sn-R2 R2 CsF, H2O/Et2O R1 R1 Easy to recycle & reuse.
  • Innovative Catalyst (III)• Polymerized ligand also could be utilized to produce recyclable heterogeneous palladium catalyst in aqueous system, like polyaniline (PANI) complexes.
  • Innovative Catalyst (III)• As well as many polymer-supported catalysts shown below.
  • Innovative Catalyst (IV)• Pd(II)/Pd(IV) high state catalytic cycle also could catalyzed coupling reactions, form C-C, C-O, C-X, C-N bonds with reasonable yields, for both alkyl and aryl groups. Angew. Chem. Int. Ed., 2009(48), pp9412 – 9423
  • Innovative Catalyst (IV)
  • Improved Condition (I)• Microwave-assisted Palladium-catalyzed cross coupling reactions have been well developed in recent years, the reaction time could be shorten a lot, yield is also improved.Suzuki Reaction: Yield: 50%-99% Ligand-Free Tetra. Lett., 2006, 47, 6887–6889
  • Improved Condition (I)
  • Improved Condition (I)• Microwave-assisted Palladium-catalyzed cross coupling reactions have been well developed in recent years, the reaction time could be shorten a lot, yield is also improved. Stille Reaction: Yield: 57%-94% Eur. J. Org. Chem., 2008, 1133–1155 Synlett., 2006, 10, 1491–1496
  • Improved Condition (II) • Besides microwave, ultrasound-promoted ligand-free Heck reaction is also investigated recently in aqueous system.The reactions finished in 20 min with high yield and good chemoselectivity without ligand. Syn. Comm., 2011, 41, pp1464–1471
  • New Reactions (I)• Some new palladium catalyzed coupling reactions have been developed in recent years. One of them is decarboxylation cross coupling reaction with aryl halide. J. AM. CHEM. SOC., 2006, 128, 11350-11351
  • New Reactions (II)• Aryl halides can be coupled with potassium oxalate monoester to synthesize aromatic esters.With different palladium salts/ligands/aryl bromides combination, the yield is up to 98%. J. Am. Chem. Soc., 2009, 131 (16), pp 5738–5739
  • New Reactions (II)• Mechanism of this reaction is also studied by theoretical calculation.
  • New Reactions (III)• Similarly, decarboxylation coupling reactions catalyzed by palladium complexes also work for sp3 carbon atom (yield is up to 96%). J. Am. Chem. Soc., 2010, 132 (41), pp 14391–14393
  • New Reactions (III)• Mechanism is also studied. The coordination of Pd activate carboxylate group.
  • New Reactions (IV)Synthesis of α-Aryl Nitriles through Palladium-Catalyzed DecarboxylativeCoupling of Cyanoacetate Salts with Aryl Halides and Triflates.
  • New Reactions (IV)
  • New Progress in PalladiumCatalyzed Coupling Reactions• List of Reactions• Mechanism of Catalysis• New Progresses• Summary
  • Summary• Palladium catalyzed coupling reactions have been widely applied in synthetic chemistry;• Mechanisms are well studied;• Reactions have been improved from different aspects, new catalysts and reactions are developed in recent years.
  • Thanks!