The Acid Effect for Pd-Catalyzed Directed C-H activation: Intimate Dialogue between Catalyst and Drecting Group
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Speaker: Tian-yu Sun Supervisor: Prof. Wu Prof. Zhang
C-H activation has been widely used
Problem: inert C-H, not good regioselectivity
green efficient Economic
Directed C-H activation
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Strong coordination: Stable Pd complex Electron-rich
weak coordination: Unstable Pd complex Electron-poor
Methods to promote reactivity: ligand, base, acid
Pd(II)-catalyzed directed C-H activation
pyridine ester
challenge
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AcOH TFA PTSA or TsOH TfOH Abbreviated:
acetic acid trifluoroacetic acid p-toluenesulfonic acid Triflic acid
pKa(H2O): -14.9 4.75 0.23 -2.8
HBF4 HPF6 PivOH: Other acids:
The acids employed to promote reactivity
Li, C.-J. et al, Chemistry – A European Journal 2014, n/a.
Lipshutz, B. H. et al, J. Am. Chem. Soc. 2010, 132, 4978.
Larrosa, I. et al, J. Am. Chem. Soc. 2008, 130, 2926.
Larrosa, I. et al, Chemistry – A European Journal 2013, 19, 15093.
Lipshutz, B. H. et al, Angew. Chem., Int. Ed. 2010, 49, 781.
acid exchange:
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TFA
trifluoroacetic acid
widely used, just several examples
long long ago
TFA for Pd-Catalyzed Directed C-H activation
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Partch, R. E. J. Am. Chem. Soc. 1967, 89, 3662.
Norman, R. O. C et al, J. Chem. Soc. B: Physical Organic 1971, 518.
The chemistry of Pb(TFA)4:
as oxidant, not catalyst
stoichiometric reaction Pb not Pd !!!
Aryl-coupling reaction
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“we chose to study the reactions of such compounds with palladium(II) in TFA in order to compare the characteristics of the two oxidants (Pd(TFA)2 and Pb(TFA)4 )”
Norman, R. O. C. et al, J. Chem. Soc., Perkin Tran. 1 1974, 1289. 7
usual phenylation
cinnamaldehyde
肉桂醛
Fujiwara, Y. et al, J. Organomet. Chem. 1982, 226, C36.
stoichiometric reaction, no oxidant
room temperature
Reaction type: carboxylation
“attributed to the formation of more electropositive Pd(TFA)+ species by use of TFA”
Fujiwara, Y. et al, J. Organomet. Chem. 1999, 580, 290.
Reaction type: Coupling of ester with benzene Directing group: none
Directing group: none
catalytic reaction
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Reaction type: Aromatic C-H Bonds for Addition to C-C Multiple Bonds Directing group: none
Fujiwara, Y. et al, Science 2000, 287, 1992. 9
the fastest rates were observed in TFA
Reaction type: arylation
Directing group: anilide
Daugulis, O. et al, Angew. Chem., Int. Ed. 2005, 44, 4046.
palladium black formation could be slowed by DMSO (10 mol %)
Buchwald, S. L. et al, Org. Lett. 2008, 10, 2207. 10
Reaction type: arylation
Directing group: ketone (weak coordination DG)
Reaction type: Trifluoromethylation
Directing group: pyridine (strong coordinationDG)
Pd(OAc)2/TFA is the best. TsOH and TfOH were not effective
Yu, J.-Q. et al, J. Am. Chem. Soc. 2010, 132, 3648.
Cheng, C.-H. et al, J. Am. Chem. Soc. 2010, 132, 8569.
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Reaction type: hydroxylation
Directing group: weak coordination DGs
first example of Pd-catalyzed C-H hydroxylation of these substrates
Rao, Y. Angew. Chem., Int. Ed. 2012, 51, 13070.
the strong acidity of TFA played a key role in this reaction
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Summary for TFA
Reaction type: Aryl-coupling, Coupling of ester with benzene, carboxylation Aromatic C-H Bonds for Addition to C-C Multiple Bonds, Arylation, Trifluoromethylation, hydroxylation
Directing group: none, anilide, ketone, pyridine, weak coordination DGs
For both weak and strong coordination DGs, TFA can promote the reactivity
electrophilic substitution??? Question:
electropositive Pd(TFA)+ species
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additives
p-toluenesulfonic acid (PSTA or TsOH)
1, lowering Temperature results in higher yields
2, TsOH > TFA > AcOH, TsOH increases electrophilicity of Pd(II)
3, NMP hamper the catalytic reaction
NMP: organic base
4, Larger amounts of TsOH promote the polymerization of alkene
0.5eq
Inspired by Fujiwara
de Vries, J. G.; van Leeuwen, P. W. N. M. et al, J. Am. Chem. Soc. 2002, 124, 1586.
Reaction type: olefination
Directing group: anilide
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halogenated acetanilides
TsOH 1 eq
Prasad, K. et al, J. Adv. Synth. Catal. 2005, 347, 1921.
Cu(OAc)2/O2 as oxidant
Liu, L.; Guo, Q.-X. et al, Tetrahedron Lett. 2007, 48, 5449.
Reaction type: olefination
Directing group: anilide
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PdCl2(MeCN)2, Interrupted Heck, indoline, low yield
TsOH·H2O (0.5equiv)
Pd(MeCN)2(OTs)2, acid-free, mild conditions
Lloyd-Jones, G. C.; Booker-Milburn, K. I. et al, J. Am. Chem. Soc. 2008, 130, 10066.
Reaction type: 1,2-Carboamination of Dienes
Directing group: urea
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TsOH was essential for catalytic turnover Room temperature
Lloyd-Jones, G. C.; Booker-Milburn, K. I. et al, Angew. Chem., Int. Ed. 2009, 48, 1830.
Reaction type: a range of coupling partners and reagents Directing group: urea
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Reaction type: Carboxylation
Directing group: anilide
NaOAc was needed???
TsOH is critical for the activation of C-H bonds under a CO environment.
Yu, J.-Q. et al J. Am. Chem. Soc. 2009, 132, 686. 18
BQ, Pd(OAc)2/TsOH(1 eq), acetone, 20℃, 20 h.
Urea is better than anilide as directing group
Brown, J. M. Chem. Commun. 2009, 3874.
Not Interrupted Heck
Reaction type: olefination
Directing group: urea
urea anilide
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Reaction type: olefination
Directing group: anilide
mechanism study : NMR, X-ray, crossover experiment
palladacycle is a true intermediate in catalysis
Mechanism: electrophilic substitution
“there is no obvious residual role for palladium acetate”
Pd(OAc)2 : Concerted Metalation−Deprotonation(CMD)
Brown, J. M. et al, Dalton Trans. 2010, 39, 10414. 20
Reaction type: Halogenation
Directing group: anilide
PTSA = TsOH =
catalytically component
Bedford, R. B. et al, Angew. Chem. Int. Ed. Engl. 2011, 50, 5524.
Room temperature
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Murata, S.; Ido, Y. Bull. Chem. Soc. Jpn. 1994, 67, 1746.
Pd(OTf)2, 1994, practical synthesized
TfOH: pKa(H2O)=-14
Superacid
TfO-: stable
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The chemistry of Pd(OTf)2
Olefin Polymerization
Sun, X.-L.; Tang, Y. et al, Chem. A Eur. J. 2013, 19, 13956.
asymmetric catalytic reactions
Kuok Hii, K. et al, Nat. Protocols 2012, 7, 1765.
alkyne hydrogenation and oligomerisation
Duckett, S. B. et al, Dalton Trans. 2008, 4270.
[Pd(OTf)2L2]
C-H activation
Ligand free
Often with ligands:
We will focus on reactions:
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Pd(II)/HOTf system is greater than AcOH or TFA
Xu, B.-Q.; White, M. G. et al, J. Catal. 1999, 187, 358.
stoichiometric reaction
1999:
Pd(OTf)2 ·2H2O better than Pd(OAc)2 NMP as the crucial promoter, mild base
Reaction type: Fluorination
Directing group: triflamide (weak coordination DG?) (strong coordination DG)
Yu, J.-Q. et al, J. Am. Chem. Soc. 2009, 131, 7520.
Reaction type: aryl coupling
Directing group: none
White, M. G. et al, J. Catal. 2000, 193, 49.
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Reaction type: Trifluoromethylation
Directing group: pyridine (strong coordination DG)
Pd(OAc)2/TFA is the best. TsOH and TfOH were not effective
Yu, J.-Q. et al, J. Am. Chem. Soc. 2010, 132, 3648.
Reaction type: Amidation
Directing group: ketone (weak coordinationDG)
HOTf to tune the electrophilicity of Pd(II)
Liu, L. et al, J. Am. Chem. Soc. 2011, 133, 1466. 25
Reaction type: arylation
Directing group: phosphate (weak coordination DG)
Moon, B. et al, J. Tetrahedron 2013, 69, 5152.
Reaction type: acylation
Directing group: amide (weak coordinationDG)
Pd(TFA)2 better than Pd(OAc)2, Pd(OTf)2 led to the decomposition
Kim, I. S. et al, Chem. Commun. 2013, 49, 1654.
acid or base
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Reaction type: Halogenation
Directing group: ??? N-Aryl-5-aminotetrazole is important
Punniyamurthy, T. et al, J. Org. Chem. 2013, 78, 6104.
Reaction type: Halogenation
Directing group: weak coordination DGs
Rao, Y. et al, Angew. Chem., Int. Ed. 2013, 52, 4440.
first example of Pd-catalyzed C-H halogenation of challenging substrates
electron-poor
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Reaction type: Halogenation
Directing group: carbamate (weak coordination DGs)
Room temperature
Rao, Y. et al, Chem. Commun. 2014, 50, 1262.
acid solvent Yield[%]
AcOH AcOH n.r.
TFA TFA 21
TfOH DCE 74
Strong DG 28
Summary for TfOH
For weak coordination DGs, TfOH can promote the reactivity
For strong coordination DGs, TfOH will quench the reaction
Pd(OTf)2 need base???
acid or base
Pd(OTf)2 ·2H2O better than Pd(OAc)2 NMP as the crucial promoter, mild base
Question:
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Thanks for your attention