O RTHO VS I PSO : S ITE -S ELECTIVE P D AND N ORBORNENE -C ATALYZED A RENE C−H A MINATION U SING A...
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Transcript of O RTHO VS I PSO : S ITE -S ELECTIVE P D AND N ORBORNENE -C ATALYZED A RENE C−H A MINATION U SING A...
Ortho vs Ipso: Site-Selective Pd and Norbornene-Catalyzed
Arene C−H Amination Using Aryl Halides
Zhe Dong and Guangbin Dong
J. Am. Chem. Soc. 2013, 135, 18350-18353.
Anne-Catherine Bédard
Charette Literature Meeting
February 5th 2014
Outline• Introduction
• The author : Guangbin Dong• Types of arene amination reactions• Catellani reaction• Meta-substituted arene
• The paper • Challenges and Optimization• Proposed Mechanism• Substrate scope• Mechanism investigation
• Conclusion
Guangbin Dong
BS, Peking University, China, 2003
PhD, Stanford University, 2009 (Trost)
Postdoc, California Institute of Technology, 2011 (Grubbs)
Assistant Prof. University of Texas at Austin (2011)
Research Interests :Catalytic Reaction Development Organometallic ChemistryNatural Product Total Synthesis
Since sept 2011 : published 15 independent papers•4 ACIE (1 VIP)•6 JACS (3 most read)
Aminations Reactions - Introduction
Types of amination reactions :
•Buchwald-Hartwig
•Nucleophilic•Electrophilic •C-H amination
This work :
Arene Aminations Reactions• Nucleophilic (via benzyne)
• Electrophilic (nitrogen source is oxidized)
Yoo, E. J.; Ma, S.; Mei, T.-S.; Chan, K. S. L.; Yu, J.-Q. J. Am. Chem. Soc. 2011, 133, 7652Campbell, M. J.; Johnson, J. S. Org. Lett. 2007, 9, 1521.
Bronner, S. M.; Goetz, A. E.; Garg, N. K. J. Am. Chem. Soc. 2011, 133, 3832
Ideal Amination ReactionAmination reactions typically need preactivation of either arene of amine
Ideal reaction : no preactivation needed !
Arene Aminations Reactions• C-H amination
• Control of the site selectivity :• Steric bias• Electronic bias• Directing group
• Mostly ortho to the DG or on the primary C-H bond.
Mei, T.-S.; Chan, K. S. L.; Yu, J.-Q. J. Am. Chem. Soc. 2009, 131, 10806.
Kantak, A. A.; Potavathri, S.; Barham, R. A.; Romano, K. M.; DeBoef, B. J. Am. Chem. Soc. 2011, 133, 19960.
Outline• Introduction
• The author : Guangbin Dong• Types of arene amination reactions• Catellani reaction• Meta-substituted arene
• The paper • Challenges and Optimization• Proposed Mechanism• Substrate scope• Mechanism investigation
• Conclusion
Catellani Reaction
Marta CatellaniPr University of Parma
Norbornene-mediated ortho C-H functionalization.
• 1985.: reaction of norbornene with bromobenzene
BrPd(PPh3)4, tBuOK
anisole, 80-105oC 65%
BrPd(PPh3)4, tBuOK
anisole, 80-105oC
F
F
F F
F1 : 3
• p-fluoro-bromobenzene leads to two isomeric products in the same conditions
Catellani, M.; Chiusoli, G. P. Organomet. Chem. 1985, 286, C13–C16.
Catellani Reaction
Catellani, M.; Frignani, F.; Rangoni, A. Angew. Chem., Int. Ed. Engl. 1997, 36, 119.Motti, E.; Rossetti, M.; Bocelli, G.; Catellani, M. J. Organomet. Chem. 2004, 689, 3741.
Palladium (IV)intermediate
Potential for meta substituted arene
Catellani Reaction
Catellani, M.; Frignani, F.; Rangoni, A. Angew. Chem., Int. Ed. Engl. 1997, 36, 119.Motti, E.; Rossetti, M.; Bocelli, G.; Catellani, M. J. Organomet. Chem. 2004, 689, 3741.
De-insertion of the norbornene is a reversible step
Catellani propose that the reduction in steric hindrance at the Pd is the driving force for the reaction
Ring strain in norbornene24-27 kcal/mol
Outline• Introduction
• The author : Guangbin Dong• Types of arene amination reactions• Catellani reaction• Meta-substituted arene
• The paper • Challenges and Optimization• Proposed Mechanism• Substrate scope• Mechanism investigation
• Conclusion
Meta-Substituted Arenes
Maimone, T. J.; Milner, P. J.; Kinzel, T.; Zhang, Y.; Takase, M. K.; Buchwald, S. L. J. Am. Chem. Soc. 2011, 133, 18106.
Electron rich aryls give higher ratio of the meta product
It was shown that the fluorating agent is 11, a modified tBuBrettPhosIntra vs intermolec mechanism still being investigated.
Meta-Substituted Arenes
Larrosa :
Cornella, J.; Righi, M.; Larrosa, I. Angew. Chem. Int. Ed. 2011, 50, 9429.Zhang, Y.-H.; Shi, B.-F.; Yu, J.-Q. J. Am. Chem. Soc, 2009, 131, 5072
Ortho arylation et decarboxylation
Yu : Electron deficient arene only
Meta-Substituted ArenesYu :
Leow, D.; Li, G.; Mei, T.-S.; Yu, J.-Q. Nature. 2012, 486, 518.Phipps, R. J.; Gaunt, M. J. Science, 2009, 323, 1593.(Mech Cu) Chen, B.; Hou, X.-L.; Li, Y.-X., Wu, Y.-D. J. Am. Chem. Soc. 2011, 133, 7668.
Gaunt :
Meta-direction removable template
Meta-Substituted Arenes : Nitrogen Substituent
Lautens :
Wilhelm, T.; Lautens, M. Org. Lett. 2005, 7, 18.Ishiyama, T.; Takagi, J.; Ishida, K.; Miyaura, N.; Anastasi, N. R.; Hartwig, J. F., J. Am. Chem. Soc. 2002, 124, 390
Hartwig :
This Paper - Challenges
• Oxidant need to provide the amine • Be stronger than aryl halide to avoid homo-Catellani reaction• Not too strong to avoid destruction of NBE or Pd(0) catalyst
• Reductant need to be orthogonal to the oxidant
Substrate Scope
b 25 mol % tri(2-furyl)phosphine, 2.0 equiv of amine and 3.0 equiv of Cs2CO3 were used.
Substrate Scope - Homodimerization
Electron poor substrate are good oxidantElectron poor phosphine decreases the formation of unwanted dimerization product
P70S6 Kinase InhibitorRetrosynthetic analysis:
Synthesis :
Hartwig :
Murphy, J. M.; Liao, X.; Hartwig, J. F., J. Am. Chem. Soc. 2007, 129, 15434.