the acid effect for pd-catalyzed directed c-h activation: intimate...

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