A Golden Catalyst For Organic Reactions

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• A Golden Catalyst For Organic Reactions

Jiaojie Li Department of Chemistry Brandeis
University
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Outline
Introduction
Gold catalyzed C-C bond formation

• Synthesis and Functionalization of arene systems
• Rearrangement and Cycloisomerization
• Carbocyclization
• Coupling Reaction

Summary
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Introduction

• Gold is an environmentally friendly catalyst, and
  it is able to catalyze reactions under mild
  conditions.
• Gold(I) and Gold(III) exhibit a soft Lewis acid
  character and a high affinity for p-bond
• Common Gold catalysts
• Gold(I) AuCl(PPh3),Au(Me)(PPh3)
• Gold(III) AuCl3, HAuCl4, NaAuCl4

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Introduction Gold catalyzed C-C bond Formation

• Synthesis and Functionalization of arene systems
• Rearrangement and Cycloisomerization
• Carbocyclization
• Coupling Reaction

Summary
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AuCl3 Catalyzed Phenol Synthesis
Hashmi, A. S. et al. J. Am. Chem. Soc. 2000, 122,
11553
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Table 1. Gold(III) Catalyzed Phenol synthesisa
a Reactions were conducted with 2-5 mol AuCl3 in
MeCN at 20?
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Proposed Mechanism
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Supporting Experiment
Hashmi A. S. et. al. Org. Lett., 2001, 3, 3769
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Advantages of Au-catalyzed Phenol Synthesis

• 1) It offers a new possibility for the
  application of Gold-catalysis in organic
  synthesis.
• 2) The old problem of a regioselective
  introduction of substituents at a benzoid arene
  now shift to furan, where such control of
  selectivity is much easier for both electrophilic
  attack and metalation.

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Application in the Synthesis of Jungianol and
epi-Jungianol
?
?
?
Hashmi A. S. et. al. Chem. Eur. J. 2003, 9, 4339
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AuCl3-Catalyzed Benzannulation

80?
Yamamoto Y. et. al. J. Am. Chem. Soc. 2002, 124,
12650
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Table2. The AuCl3-Catalyzed Benzannulationa
a Reactions were conducted with 1 equiv
o-alkynylbenzaldehydes , 3 equiv alkynes and 3
mol AuCl3 in dichloroethane at 80 ? for 2-24h.
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1a) R Me 40
1b)
R Ph 60
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Proposed Mechanism
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Regioselective Discussion
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Au-Catalyzed Cyclialkylation of Electron-Rich
Arenes
,?
He C. et. al. J. Am. Chem. Soc. 2004, 126, 5964
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Table 3. Gold(III)-Catalyzed Intramolecular
Cyclialkylationa
a Reactions were conducted with 0.5mmol of
oxiranes and 2.5 mol of AuCl3/ 3AgOTf in 3ml of
dichloroethane for 4h, the temperature is from
50? to 80? .
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Direct Functionalization of Arenes
ClCH2CH2Cl, 120?
He C. et. al. J. Am. Chem. Soc. 2004, 126, 13596
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Table 4. Gold-Catalyzed Functionalization of
Arenesa
a Reactions were conducted at 120? in DCE with
0.5mmol of arenes, 1mmol of sulfonate ester, and
5 mol AuCl3/3AgOTf for 48h.
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Two Competing Mechanisms
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Control Experiment
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Gold-Catalyzed Addition of Arenes to Imines
Li C. J. et. al. Chem. Commun., 2004, 1930
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Table 5. Gold-catalyzed Addition of
Arenes to Iminesa
a Reactions were conducted with 3mol
AuBr3/3AgOTf at 50? to 80? .
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Introduction Gold catalyzed C-C bond Formation

• Synthesis and Functionalization of arene systems
• Rearrangement and Cycloisomerization
• Carbocyclization
• Coupling Reaction

Summary
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Background of Claisen Rearrangement

• Lewis acid catalyzed Claisen rearrangement
• Hard Lewis acids, which catalyze the reaction by
  coordination to Oxygen atom.
• Soft Lewis acids, such as Pd(II) and Hg(II),
  which catalyze the reaction by coordination to
  ?-bond.

However, it is often limited by binding of
electronphilic metal center to strong
nucleophilic vinyl ethers, thus prevents the
activation of ?-bond.
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Gold(I)-Catalyzed Propargyl Claisen Rearrangement
Toste F. D. et. al. J. Am. Chem. Soc. 2004, 126,
15978
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Table 6 Au(I)-Catalyzed Propargyl Claisen
Rearrangementa
1)
2)
a Reactions were conducted with 0.1
mol(Ph3PAu)3OBF4 at 75? in dichloroethane for
1-25h.
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Control Reactions
?
(Ph3PAu)3OBF4(1mol),CH2Cl2, 4h, 40? 81
gt 201dr NaBH4, MeOH, R.T. PhCH3, 3h, 170 ?
NaBH4, MeOH, R.T. 90 11.5dr
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Proposed Mechanism for the Au(I)-Catalyzed
Rearrangement
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Gold(I)-Catalyzed Isomerization of 1,5-Enynes
Toste F. D. et. al. J. Am. Chem. Soc. 2004, 126,
10858
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Table 7. Au(I)-Catalyzed Synthesis of
Bicyclo3.1.0hexenesa
a Reactions were conducted with 0.5M 1,5-enyen
and 1-3mol (PPh3)Au(I) in dichloroethane for
2-24h, rt.
To be continued
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continue
a Reactions were conducted with 0.5M 1,5-enyen
and 1-3mol (PPh3)Au(I) in dichloroethane for
2-24h, rt
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Proposed Mechanism for Au(I)-Catalyzed
Cycloisomerization
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Introduction Gold catalyzed C-C bond Formation

• Synthesis and Functionalization of arene systems
• Rearrangement and Cycloisomerization
• Carbocyclization
• Coupling Reaction

Summary
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Gold(I)-Catalyzed Carbocyclization
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Gold(I)-Catalyzed 5-exo-dig Cyclization
Toste F. D. et. al. J. Am. Chem. Soc. 2004, 126,
4526
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Table 8. Gold(I)-Catalyzed 5-exo-dig cyclizationa
a Reactions were conducted with 1 mol(PPh3)AuCl,
1 molAgOTf, 0.4M ketoester in dichloromethane,
rt.
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Mechanistic Hypotheses
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Gold(I)-Catalyzed 5-endo-dig Carbocyclization

No reaction lt 5 conversion 93 yield
Toste, F. D. et. al. Angew. Chem. Int. Ed. 2004,
43, 5350.
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Table 9. Au(I)-Catalyzed 5-endo-dig
carbocyclizationa
aReactions were conducted with 1 mol(PPh3)AuCl,
1 molAgOTf, 1.0M ketoester in dichloromethane,
rt.
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Mechanistic Comparison for the Gold(I)-Catalyzed
Carbocyclization
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Introduction Gold catalyzed C-C bond Formation

• Synthesis and Functionalization of arene systems
• Rearrangement and Cycloisomerization
• Carbocyclization
• Coupling Reaction

Summary
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Au(I)-Catalyzed three-Component Coupling of
Aldehydes, Alkynes and Amines
Li, C.J. et. al. J. Am. Chem. Soc. 2003, 125,
9584
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Table10. Gold-Catalyzed Coupling of Aldehydes,
Alkynes and Amines in watera
a Reactions were conducted with 1 mol AuCl at
75? in water for 12h.
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Proposed Mechanism
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Summary

• Both Gold(I) and Gold(III) complexes exhibit a
  high ability for alkyne activation.
• Gold salts can also activate the C-H bond of
  electron-rich arenes.
• Most of Gold-catalyzed reactions can proceed in
  mild conditions.

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Thank You!
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Hashmi A. S. et. al. Org. Lett., 2001, 3, 3769
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Table 5. Gold-Catalyzed intramolecular
Cyclialkylation