Synthesis and Functionalization of Indoles From Palladium-Catalyzed Reactions

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Synthesis and Functionalization of Indoles From
Palladium-Catalyzed Reactions

• Literature meeting
• Marie-Noelle Roy
• October 11th, 2005

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Content
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• Formation of the Pyrrole Nucleus Contained in the
  Indole System
• Cyclization of Alkynes
• Cyclization of Alkenes
• Functionalization of Pre-formed Indole System

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3
?- Complexation
?- Complexation
Oxidative Addition
?- allyl Complexation
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Retrosynthetic Scheme Based on Pd-Catalysis
Formation of the Pyrrole Ring from Alkyne
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Cyclization of o-Alkynylanilides Catalyzed by
Pd(II) Salt
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Cyclization of o-Alkynylanilides Catalyzed by
Pd(II) Salt
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Mechanism
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Cyclization of o-Alkynylanilides Catalyzed by
Pd(II) Salt
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Cyclization of o-Alkynylanilides Catalyzed by
Pd(II) Salt
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Mechanism
Pd(II) have a dual role catalyst
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Cyclization of o-Alkynylanilides Catalyzed by
Pd(II) Salt
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Proposed Mechanism
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Cyclization of o-Alkynylanilides Catalyzed by
Pd(II) Salt
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Proposed Mechanism
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Cyclization of o-Alkynylanilides via
Aminopalladium-Reductive Elimination
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Cyclization of o-Alkynylanilides via
Aminopalladium-Reductive Elimination
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Cyclization of o-Alkynylanilides via
Aminopalladium-Reductive Elimination
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General Mechanism
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Cyclization of o-Alkynylanilides via
Aminopalladium-Reductive Elimination
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Cyclization of o-Alkynylanilides via
Aminopalladium-Reductive Elimination
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Proposed Mechanism
Up to 40 oC
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Cyclization of o-Alkynylanilides via
Aminopalladium-Reductive Elimination
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Proposed Mechanism
- N2
Pd(0)
100 oC
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Cyclization of o-Alkynylanilides via
Aminopalladium-Reductive Elimination
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Cyclization of o-Alkynylanilides via
Aminopalladium-Reductive Elimination
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Proposed Mechanism

• Without Pd the reaction doesnt
• take place
• 2. CuCl is needed the formation
• of the indole
• Aminopalladation must proceed
• by a trans manner

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Intermolecular Cycloaddition of o-Iodoanilides
with Internal Alkynes
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Intermolecular Cycloaddition of o-Iodoanilides
with Internal Alkynes
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Intermolecular Cycloaddition of o-Iodoanilides
with Internal Alkynes
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Proposed Mechanism
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Intermolecular Cycloaddition of o-Iodoanilides
with Internal Alkynes
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Intermolecular Cycloaddition of o-Iodoanilides
with Internal Alkynes
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Proposed Mechanism
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Cyclization of o-Alkyl-N-alkylidene-anilines
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Cyclization of o-Alkyl-N-alkylidene-anilines
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Cyclization of o-Alkyl-N-alkylidene-anilines
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Proposed Mechanism
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Cyclization of o-Halo-N-Alkynylanilides
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Cyclization of o-Halo-N-Alkynylanilides
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Cyclization of o-Halo-N-Alkynylanilides
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Proposed Mechanism
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Cyclization of o-Iodo-N-Propargylanilides
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Cyclization of o-Iodo-N-Propargylanilides
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Proposed Mechanism
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Retrosynthetic Scheme Based on Pd-Catalysis
Formation of the Pyrrole Ring from Alkene
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Cyclization of o-Halo-N-allylanilines
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Proposed Mechanism
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Cyclisation of o-Haloanilino Enamines
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Intramolecular Cyclisation of o-Iodoanilines in
Presence of Allene
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Intramolecular Cyclisation of o-Iodoanilines in
Presence of Allene
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Proposed Mechanism
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Cyclisation of o-Allylanilines, o-Vinylanilines
and Nitrostyrenes
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Cyclization of o-Allylanilines
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Proposed Mechanism
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Cyclisation of o-Vinylanilines
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Cyclization of Nitrostyrenes
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Cyclisation of o-Vinylphenyl Isocyanide
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Cyclization of o-Vinylphenyl Isocyanide
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Proposed Mechanism
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Functionalization of the Pre-formed Indole System
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Heck Cross-Coupling Reaction
Sonogashira Cross-Coupling Reaction
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Functionalization of the Pre-formed Indole System
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Stille Cross-Coupling Reaction
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Functionalization of the Pre-formed Indole System
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Suzuki Cross-Coupling Reaction
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Functionalization of the Pre-formed Indole System
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Negishi Cross-Coupling Reaction
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Conclusion
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• The pyrrole ring of Indole can be synthesized by
  many different Pd- catalyzed approaches using
  both alkynes and alkenes as substrates
• Indole core can be easily functionalized by
  classical cross-coupling reaction
• Pd-Catalyzed reactions tolerate a wide range of
  functionalities
• Indole chemistry have a considerable impact in
  the synthesis of biologically active compounds