Direct β-Functionalization of Carbonyl Compounds · PDF file 2014-02-04 ·...

Click here to load reader

  • date post

    15-Mar-2020
  • Category

    Documents

  • view

    4
  • download

    0

Embed Size (px)

Transcript of Direct β-Functionalization of Carbonyl Compounds · PDF file 2014-02-04 ·...

  • Direct β-Functionalization of Carbonyl Compounds

    Yijing Dai Jan 08. 2014

  • Carbonyl Compounds

    L.G. Wade, Jr. Organic Chemistry, 5th ed. Prentice Hall, 2002. ISBN 0-13-033832-X

  • Direct Functionalization of Carbonyl Compounds

    Aldehyde & Ketone

    ●ipso position-Grignard reaction, Wittig olefinations, reductive aminations ●α position-Enolate chemistry (Aldol reaction, Pd-catalyzed α-arylation ) ●β position-?

    Carboxylic & Acid & Ester

    ●ipso position-, Nucleophilic addition, reduction ●α position-Halogenation, Claisen Condensation ●β position-?

  • Outline

    q  Direct β-Functionalization of Ketone and Aldehyde

    Ø  Organocatalysis and Photoredox Process

    Ø  Palladium-Catalyzed β-Arylation

    q  Direct β-Functionalization of Carboxylic Acid and Ester

    Ø  Palladium-Catalyzed β-Arylation of Simple Carboxylic Acids

    Ø  Palladium-Catalyzed β-Functionalized Esters

  • Conventional β-Functionalization of Ketone and Aldehyde

    α-functionalization

    β-functionalization

    Conventional approach

    Huang, Z.;Dong, G. J. Am. Chem. Soc., 2013, 135, 17747–17750

  • Outline

    q  Direct β-Functionalization of Ketone and Aldehyde

    Ø  Organocatalysis and Photoredox Process

    Ø  Palladium-Catalyzed β-Arylation (Pd-enolate)

    q  Direct β-Functionalization of Carboxylic Acid and Ester

    Ø  Palladium-Catalyzed β-Arylation of Simple Carboxylic Acids

    Ø  Palladium-Catalyzed β-Functionalized Esters

  • Three Activation Mode of Organocatalysis

    Zhang, S.-L.; Xie, H.-X.; Zhu, J.; Li, H.; Zhang, X.-S.; Li, J.; Wang, W. Nat. Commun. 2011, 2, 211

    HOMO Activation

    LUMO Activation

    SOMO Activation

  • β-Functionalization Aldehyde by Oxidative Enamine Catalysis

    Zhang, S.-L.; Xie, H.-X.; Zhu, J.; Li, H.; Zhang, X.-S.; Li, J.; Wang, W. Nat. Commun. 2011, 2, 211

  • β-Functionalization of Aldehydes by FBSM

    Zhang, S.-L.; Xie, H.-X.; Zhu, J.; Li, H.; Zhang, X.-S.; Li, J.; Wang, W. Nat. Commun. 2011, 2, 211

  • Oxidative Enamine in Cascade Processes

    Zhang, S.-L.; Xie, H.-X.; Zhu, J.; Li, H.; Zhang, X.-S.; Li, J.; Wang, W. Nat. Commun. 2011, 2, 211

  • Oxidative Enamine in Cascade Processes

    Zhang, S.-L.; Xie, H.-X.; Zhu, J.; Li, H.; Zhang, X.-S.; Li, J.; Wang, W. Nat. Commun. 2011, 2, 211

    quadruple cascade: oxidation-Michael-Aldol-Dehydration process

  • Mechanism Study

    Zhang, S.-L.; Xie, H.-X.; Zhu, J.; Li, H.; Zhang, X.-S.; Li, J.; Wang, W. Nat. Commun. 2011, 2, 211

  • Possible Mechanisms

    Single electron transfer (SET) pathway

    Zhang, S.-L.; Xie, H.-X.; Zhu, J.; Li, H.; Zhang, X.-S.; Li, J.; Wang, W. Nat. Commun. 2011, 2, 211

    CAN: Cerium (IV) ammonium nitrate

    Standard SET Pathway by MacMillan

    Beeson,T. D. ; Mastracchio, A.; Hong, J.; Ashton, K.; MacMillan, D. W. C. Science, 2013, 339, 1593

  • Possible Mechanisms

    Ionic process involving an electron pair transfer

    Zhang, S.-L.; Xie, H.-X.; Zhu, J.; Li, H.; Zhang, X.-S.; Li, J.; Wang, W. Nat. Commun. 2011, 2, 211

    IBX-mediate oxidation pathway

    Dess, D. B.; Martin, J. C. J. Am. Chem. Soc. 1991, 113, 7277–7287

  • Photoredox Activation for β-Arylation of Ketones and Aldehydes

    Pirnot, M. T.; Rankic, D. A.; Martin, D. B. C.; MacMillan, D. W. C. Science, 2013, 339, 1593

  • Proposed Activation Mode

    SET

    SET

    Pirnot, M. T.; Rankic, D. A.; Martin, D. B. C.; MacMillan, D. W. C. Science, 2013, 339, 1593

  • β-Arylation of Different Aldehydes

    Pirnot, M. T.; Rankic, D. A.; Martin, D. B. C.; MacMillan, D. W. C. Science, 2013, 339, 1593

  • β-Arylation of Different Ketones

    Pirnot, M. T.; Rankic, D. A.; Martin, D. B. C.; MacMillan, D. W. C. Science, 2013, 339, 1593

  • β-Functionalization of Cyclic Ketones with Aryl Ketones

    Petronijević, F. R.; Nappi, M.; MacMillan, D. W. C. J. Am. Chem.Soc., 2013, 135, 18323–18326

  • Proposed Mechanism

    SET

    SET

    Petronijević, F. R.; Nappi, M.; MacMillan, D. W. C. J. Am. Chem.Soc., 2013, 135, 18323–18326

  • Scope of the Ketone-Radical Precursor

    Petronijević, F. R.; Nappi, M.; MacMillan, D. W. C. J. Am. Chem.Soc., 2013, 135, 18323–18326

  • Scope of Ketyl Radical Coupling Partner

    Petronijević, F. R.; Nappi, M.; MacMillan, D. W. C. J. Am. Chem.Soc., 2013, 135, 18323–18326

  • Stern-Volmer Quenching Studies for Mechanism

    Figure 1. *Ir(ppy)3 emission quenching with benzophenone and enamine 4.

    Figure 2. *Ir(p-MeO-ppy)3 emission quenching with acetophenone and enamine 4.

    Petronijević, F. R.; Nappi, M.; MacMillan, D. W. C. J. Am. Chem.Soc., 2013, 135, 18323–18326

  • An Alternative Mechanism for Alkyl-Aryl Ketone

    SET

    SET

  • Outline

    q  Direct β-Functionalization of Ketone and Aldehyde

    Ø  Organocatalysis and Photoredox Process

    Ø  Palladium-Catalyzed β-Arylation (Pd-enolate)

    Ø  Direct β-Functionalization of Carboxylic Acid and Ester

    Ø  Palladium-Catalyzed β-Arylation of Simple Carboxylic Acids

    Ø  Palladium-Catalyzed β-Functionalized Esters

  • Proposed Mechanism

    Huang, Z.;Dong, G. J. Am. Chem. Soc., 2013, 135, 17747–17750

  • Substrate Scope

    Huang, Z.;Dong, G. J. Am. Chem. Soc., 2013, 135, 17747–17750

  • Synthesis of Intermediate for SERT Antagonist

    Huang, Z.;Dong, G. J. Am. Chem. Soc., 2013, 135, 17747–17750

  • Conclusion

  • Outline

    q  Direct β-Functionalization of Ketone and Aldehyde

    Ø  Organocatalysis and Photoredox Process

    Ø  Palladium-Catalyzed β-Arylation (Pd-enolate)

    Ø  Direct β-Functionalization of Carboxylic Acid and Ester

    Ø  Palladium-Catalyzed β-Arylation of Simple Carboxylic Acids

    Ø  Palladium-Catalyzed β-Functionalized Esters

  • Transition-Metal-Catalyzed C-H Functionalization

    Jazzar, R.; Hitce, J.; Renauda,A.; Sofack-Kreutze,J.; Baudoin, O. Chem. Eur. J. 2010, 16, 2654 – 2672

    Shang, R.; Ilies, L.; Matsumoto, A..; Nakamura, E. J. Am. Chem. Soc. 2013, 135, 6030−6032

  • Outline

    q  Direct β-Functionalization of Ketone and Aldehyde

    Ø  Organocatalysis and Photoredox Process

    Ø  Palladium-Catalyzed β-Arylation (Pd-enolate)

    Ø  Direct β-Functionalization of Carboxylic Acid and Ester

    Ø  Palladium-Catalyzed β-Arylation of Simple Carboxylic Acids

    Ø  Palladium-Catalyzed β-Functionalized Esters

  • Direct β-Functionalization of Carboxylic Acids

    This coupling reaction provides the first example for carboxyl-directed Pd-insertion into sp3 -β-C-H bonds in simple aliphatic acids

    R. Giri, N. Maugel, J.-J. Li, D.-H. Wang, S. P. Breazzano, L. B. Saunders, J.-Q. Yu, J. Am. Chem. Soc. 2007, 129, 3510 – 3511

  • Three Coordination Modes of Pd(II) with Carboxylic Acids

    Chen, X.; Engle, K. M.; Wang, D.; Yu, J. Angew. Chem. Int. Ed. 2009, 48, 5094 – 5115

  • Proposed Mechanism

  • Outline

    q  Direct β-Functionalization of Ketone and Aldehyde

    Ø  Organocatalysis and Photoredox Process

    Ø  Palladium-Catalyzed β-Arylation (Pd-enolate)

    Ø  Direct β-Functionalization of Carboxylic Acid and Ester

    Ø  Palladium-Catalyzed β-Arylation of Simple Carboxylic Acids

    Ø  Palladium-Catalyzed β-Functionalization of Esters

  • Pd-Catalyzed α or β-Functionalization of Carboxylic Esters

    A. Renaudat, L. Jean-Grard, R. Jazzar, C. E. Kefalidis, E. Clot, O. Baudoin, Angew. Chem. 2010, 122, 7419 – 7423

  • Initial Study

    A. Renaudat, L. Jean-Grard, R. Jazzar, C. E. Kefalidis, E. Clot, O. Baudoin, Angew. Chem. 2010, 122, 7419 – 7423

  • Ligands Study

    A. Renaudat, L. Jean-Grard, R. Jazzar, C. E. Kefalidis, E. Clot, O. Baudoin, Chem. Eur. J. 2012, 18, 1932 – 1944

  • Ligands Study

    A. Renaudat, L. Jean-Grard, R. Jazzar, C. E. Kefalidis, E. Clot, O. Baudoin, Chem. Eur. J. 2012, 18, 1932 – 1944

  • Electronic Effect Study

    A. Renaudat, L. Jean-Grard, R. Jazzar, C. E. Kefalidis, E. Clot, O. Baudoin, Chem. Eur. J. 2012, 18, 1932 – 1944

  • Proposed Mechanism

    A. Renaudat, L. Jean-Grard, R. Jazzar, C. E. Kefalidis, E. Clot, O. Baudoin, Chem. Eur. J. 2012, 18, 1932 – 1944

  • DFT Calculation

    Gibbs free energy (kcal  mol−1) diagram for the α- and β-arylation pathways (L=PCy3, Ar=2-fluorophenyl).

    A. Renaudat, L. Jean-Grard, R. Jazzar, C. E. K