Organic Seminar Recent Advances in Ni Catalyzed Suzuki Coupling: Toward Green, Cheap and Environmentally Friendly Catalysis Chun Ho Lam 2 nd November, 2011 1
Organic Seminar
Recent Advances in Ni Catalyzed Suzuki Coupling:
Toward Green, Cheap and Environmentally Friendly Catalysis
Chun Ho Lam
2nd November, 2011
1
The Palladium Coupling Reactions
Ni0
2
The Popularity of Cross Coupling Reaction
Colacot, T.J. Platinum Metals Rev., 2011, 55, 84–90. 3
Advantages of Suzuki Coupling Over Others
The use of Boron Coupling Partner over others:
Mild Reagent
Relatively Non-Toxic
Many Organoboronic acids are commercially available
Tolerate a lot of functional groups
Comparatively, Moderately Air Stable
Rosen, B. M.; Quasdorf, K. W.; Wilson, D. A.; Zhang, N.; Resmerita, A.-M.;
Garg, N. K.; Percec, V. Chem. Rev. 2011, 111, 1346–1416. 4
Leaving Group:
• Oxidative Addition
• Reactivity
• Ar-X: I >> Br > Cl
The Research Focus on Suzuki Coupling:
Using Suzuki Coupling as an Example:
Ligand Metal Complex
(In particular to the Ligand)
• Solubility
• Air Stability
• Reactivity
• Stereo Selectivity
Boronic Partner:
• (R = H) Boronic Acid
• (R = Alkyl) Boronic Ester
Coupling Group
• Aryl
• Allyl
• Alkyl
• Hetero
Rosen, B. M.; Quasdorf, K. W.; Wilson, D. A.; Zhang, N.; Resmerita, A.-M.;
Garg, N. K.; Percec, V. Chem. Rev. 2011, 111, 1346–1416. 5
Consideration on Group 10 Metals: Ni, Pd
Why Nickel?
Why not Nickel?
USD mol-1 Abundance Est. Electronic Config. Possible Oxi. State
Ni $1.20 84 mg / kg [Ar] 3d8 4s2 0, +2 (+1,+3)
Pd $1,500 0.02 mg / kg [Kr] 4d10 (Not 4d8 5s2) 0, +2 (+1, +4)
Cat. Loading Ligand Extra Ligand Loading Extraction
Ni 5 – 10 mol% 1 – 4 equiv Always Difficult
Pd 0.1 – 5 mol% 1 – 4 equiv Sometimes Moderate
Rosen, B. M.; Quasdorf, K. W.; Wilson, D. A.; Zhang, N.; Resmerita, A.-M.;
Garg, N. K.; Percec, V. Chem. Rev. 2011, 111, 1346–1416. 6
Common Leaving Groups in Suzuki Reaction
Palladium Nickel
Halides: -Cl, -Br, -I
Enol/Phenol Derivatives : -OTf, -OMs, -OTs, -OP(O)(OR)2
Esters: -OC(O)R
Sulfamate: -OSO2NR2
Carbamate:-OC(O)NR2
Ether: -OR
Jana, R.; Pathak, T. P.; Sigman, M. S. Chem. Rev. 2011, 111, 1417–1492. 7
Common Leaving Group:
Notes:
Seminar Outline
Part 1
Suzuki Cross Coupling of Aryl Carbamate and Aryl Sulfamate
Ox. Addition Selectivity Towards the Guided Site
Room Temperature Catalyzed Inactivated Electrophile
Part 2
Suzuki Cross Coupling of Aryl Ether
Reductive Demethoyxlation in Aryl Ether
Possible Application in non-synthetic area
8
Suzuki Cross-Coupling of Aryl Carbamates
Selected Examples:
Sensitive to steric hindrance, and the substitution effect
Quasdorf, K. W.; Antoft-Finch, A.; Liu, P.; Silberstein, A. L.; Komaromi, A.; Blackburn, T.;
Ramgren, S. D.; Houk, K. N.; Snieckus, V.; Garg, N. K. J. Am. Chem. Soc. 2011, 133, 6352-6363. 9
Suzuki Cross-Coupling of Aryl Sulfamates
Insensitive to EWG and EDG, and Steric
Selected Examples:
10 Quasdorf, K. W.; Antoft-Finch, A.; Liu, P.; Silberstein, A. L.; Komaromi, A.; Blackburn, T.;
Ramgren, S. D.; Houk, K. N.; Snieckus, V.; Garg, N. K. J. Am. Chem. Soc. 2011, 133, 6352-6363.
Study of Oxidative Addition of Ni(PPh3)2
Hammett Plot on Relative Rates of Ox. Addition:
Foa, M.; Cassar, L. J. Chem. Soc.-Dalton Trans. 1975, 23, 2572-2576.
The Experiment:
The Purpose - See the Effect of Substitute
EW
11
DFT Analysis: Oxidative Addiction Mechanism
12
Carbamate:
Sulfamate:
•5-Centered TS is more
favorable vs. 3-Centered
•Sulfamate higher
reactivity results in the
more stable T.S.
• Phosphorus
• Nickel
• Oxygen
• Nitrogen
• Carbon
• Sulfur
• Hydrogen
Quasdorf, K. W.; Antoft-Finch, A.; Liu, P.; Silberstein, A. L.; Komaromi, A.; Blackburn, T.;
Ramgren, S. D.; Houk, K. N.; Snieckus, V.; Garg, N. K. J. Am. Chem. Soc. 2011, 133, 6352-6363.
Cy Ligand
DFT Analysis: Selective Oxidation Addition
Carbamate:
Sulfamate:
13 Quasdorf, K. W.; Antoft-Finch, A.; Liu, P.; Silberstein, A. L.; Komaromi, A.; Blackburn, T.;
Ramgren, S. D.; Houk, K. N.; Snieckus, V.; Garg, N. K. J. Am. Chem. Soc. 2011, 133, 6352-6363.
• Phosphorus
• Nickel
• Oxygen
• Nitrogen
• Carbon
• Sulfur
• Hydrogen
Ox. Addition
Selectivity?
• Higher coordination => Lower T.S.
Energy
• Coordination dictates the site where
Ox. Addition occurs
• Interesting to see how Pd coordinate
and its relative energetic.
Inertness Towards Palladium
Quasdorf, K. W.; Antoft-Finch, A.; Liu, P.; Silberstein, A. L.; Komaromi, A.; Blackburn, T.;
Ramgren, S. D.; Houk, K. N.; Snieckus, V.; Garg, N. K. J. Am. Chem. Soc. 2011, 133, 6352-6363. 14
An strategic synthesis example:
Seminar Outline
Part 1
Suzuki Cross Coupling of Aryl Carbamate and Aryl Sulfamate
Ox. Addition Selectivity Towards the Guided Site
Room Temperature Catalyzed Inactivated Electrophile
Part 2
Suzuki Cross Coupling of Aryl Ether
Reductive Demethoyxlation in Aryl Ether
Possible Application in non-synthetic area
15
Ni. Cat. Non-Aromatic sp3 Suzuki Coupling
Selected Examples:
• EWG & EDG have
minor effects
• Ester and OPiv are
Vulnerable
• Selectively on α-aliphatic pivalate
Huang, K.; Li, G.; Huang, W.-P.; Yu, D.-G.; Shi, Z.-J. Chem. Commun. 2011, 47, 7224-7226. 16
Suggested Mechanism for the Catalytic Cycle
Huang, K.; Li, G.; Huang, W.-P.; Yu, D.-G.; Shi, Z.-J. Chem. Commun. 2011, 47, 7224-7226. 17
Suggested Di-Oxygen Guided Insertion
Selective Activation is dictated from stability of the T.S.
Huang, K.; Li, G.; Huang, W.-P.; Yu, D.-G.; Shi, Z.-J. Chem. Commun. 2011, 47, 7224-7226. 18
Coordination Similar to the Ar-Carbamate
(56%)
Seminar Outline
Part 1
Suzuki Cross Coupling of Aryl Carbamate and Aryl Sulfamate
Ox. Addition Selectivity Towards the Guided Site
Room Temperature Catalyzed Inactivated Electrophile
Part 2
Suzuki Cross Coupling of Aryl Ether
Reductive Demethoyxlation in Aryl Ether
Possible Application in non-synthetic area
19
Room Temp. Catalyzed Inactivated Suzuki Reaction
Xing, C.-H.; Lee, J.-R.; Tang, Z.-Y.; Zheng, J. R.; Hu, Q.-S. Adv. Synth. Catal. 2011, 353, 2051-2059. 20
The Thinking Trail:
Catalyst Conversion (%)
Pd2(dba)3 + 0
Pd2(dba)3 + 0
Ni(COD)2 + 0
Ni(COD)2 0
Ni(COD)2 + Dppe or Dppf 0
Ni(PCy3)2Cl2 + 2 PCy3 11
Ni(COD)2 + 2 PCy3 90 (6hrs), 99 (24hrs)
Tang, Z.-Y.; Hu, Q.-S. J. Am. Chem. Soc. 2004, 126, 3058-3059. 21
Room Temp. Ni Catalyzed Suzuki Coupling
Xing, C.-H.; Lee, J.-R.; Tang, Z.-Y.; Zheng, J. R.; Hu, Q.-S. Adv. Synth. Catal. 2011, 353, 2051-2059. 22
The Importance of Water
0
10
20
30
40
50
60
0 1 2 3 4 5
Yie
ld (
%)
H2O Additive (Equiv)
Effect of Water in Ni Cat. Suzuki Cross Coupling
Xing, C.-H.; Lee, J.-R.; Tang, Z.-Y.; Zheng, J. R.; Hu, Q.-S. Adv. Synth. Catal. 2011, 353, 2051-2059. 23
The Importance of Water in Suzuki Coupling
1st equiv of water:
R-B(OH)2 R-B(OH)3-
2nd equiv of water: Lower the
energy of 29 of the
transmetallation step by 17 kcal
mol-1
Quasdorf, K. W.; Antoft-Finch, A.; Liu, P.; Silberstein, A. L.; Komaromi, A.; Blackburn, T.;
Ramgren, S. D.; Houk, K. N.; Snieckus, V.; Garg, N. K. J. Am. Chem. Soc. 2011, 133, 6352-6363. 24
In Excessive Amount of Water
At Room Temp.
Ni(PCy3)2Br2 + 2 H2O(xs) Ni(OH)2 + 2PCy3.HBr
(Pale Green) (Colorless)
At High Temp.
Ni(PCy3)2Br2 + 2 H2O(xs) Ni(OH)2 + 2PCy3.HBr
(Pale Green) (Colorless)
Solubility:
Ni(OH)2 << NiBr2 (Room Temperature)
Enough Water is Crucial!
Too much water will hydrate catalyst, shuts down catalytic cycle
Optimal Amount is 2 equivalent (to Ar-X)
Xing, C.-H.; Lee, J.-R.; Tang, Z.-Y.; Zheng, J. R.; Hu, Q.-S. Adv. Synth. Catal. 2011, 353, 2051-2059. 25
Conclusion for Part 1
Compatibility:
• Ni can be a viable replacement for Pd
Oxidative Addition favors:
•Electronic deficient ring
•Favors at site where Metal coordinate the best. (Lowest Energy)
H2O is significant to Suzuki coupling at room temperature:
•2 equiv (to the Electrophile)
•1st equiv generates HO- for Borate
•2nd equiv lowers the energy of T.S. in Transmetallation
•Too much MAY diminish catalytic effect at low temperature.
Selectivity:
• Ni: Sulfamate, Carbamate, Ether
26
Seminar Outline
Part 1
Suzuki Cross Coupling of Aryl Carbamate and Aryl Sulfamate
Ox. Addition Selectivity Towards the Guided Site
Room Temperature Catalyzed Inactivated Electrophile
Part 2
Suzuki Cross Coupling of Aryl Ether
Reductive Demethoyxlation in Aryl Ether
Possible Application in non-synthetic area
27
Part 2: Suzuki Coupling with Alkyl-Ether
(Chatani, 2008)
Tobisu, M.; Shimasaki, T.; Chatani, N. Angew. Chem. Int. Ed. 2008, 47, 4866-4869. 28
(Fu, 1999)
Suzuki Coupling of Aryl Ether
29
• Favors at Polyaromatics Site
• Very sensitive to EWG
Tobisu, M.; Shimasaki, T.; Chatani, N. Angew. Chem. Int. Ed. 2008, 47, 4866-4869.
Effect of the Secondary Alkyl Group.
R Group Yield (%)
Me 93
Et 76
iPr 16
Activation is most likely
sensitive to
• Ester Group
• Other Ether Group
Tobisu, M.; Shimasaki, T.; Chatani, N. Angew. Chem. Int. Ed. 2008, 47, 4866-4869. 30
Oxidative Addition: The Rate Determining Steps
• Yield is almost independent from nature of the boronic ester (EDG vs. EWG)
• Oxidative Addition is most likely the R.D.S
• Note: R.D.S. may vary in different system
Tobisu, M.; Shimasaki, T.; Chatani, N. Angew. Chem. Int. Ed. 2008, 47, 4866-4869. 31
Strategic Synthetic Application
Tobisu, M.; Shimasaki, T.; Chatani, N. Angew. Chem. Int. Ed. 2008, 47, 4866-4869. 32
The Limitation on C(aryl)-OMe Activation
Ni Coordination to aromatic system helps to activate
the C(aryl)-OMe bond cleavage
33 Tobisu, M.; Shimasaki, T.; Chatani, N. Angew. Chem. Int. Ed. 2008, 47, 4866-4869.
Seminar Outline
Part 1
Suzuki Cross Coupling of Aryl Carbamate and Aryl Sulfamate
Ox. Addition Selectivity Towards the Guided Site
Room Temperature Catalyzed Inactivated Electrophile
Part 2
Suzuki Cross Coupling of Aryl Ether
Reductive Demethoyxlation in Aryl Ether
Possible Application in non-synthetic area
34
The use of Ni in Other Synthetic Purposes
Nickel can achieve Oxidative Addition in C(aryl)-O Bond
Possible Synthetic Applications:
P. A’lvarez-Bercedo, R. Martin, J. Am. Chem. Soc. 2010, 132, 17 352-17353. 35
Nickel Catalyzed Reductive Demethoxylation:
Temporary
Directing Group
Examples of Demethoxylation
P. A’lvarez-Bercedo, R. Martin, J. Am. Chem. Soc. 2010, 132, 17 352-17353. 36
Selectivity in C(aryl)-O Activation with Ni
37 P. A’lvarez-Bercedo, R. Martin, J. Am. Chem. Soc. 2010, 132, 17 352-17353.
• Potentially Destroy Aromaticity • Potentially Destroy Aromaticity
• Guided by Ester Group
• Partially Destroy Aromaticity
• Possibly Guided by –OMe
• Selective towards sp2, but not
perfect
• Partially Destroy Aromaticity
• Guided by Ester Group
• Guiding increases selectivity,
but not perfect.
Case 1: Case 2:
Case 3: Case 4:
Deuterium Confirmation
1. C(aryl) – OMe can be activated by nickel selectively (not Pd)
2. Activation most likely involves coordination
3. Polyaromatic system favors activation vs. mono aromatic
4. Favors sp2 vs. sp3
5. A new way to label compound
P. A’lvarez-Bercedo, R. Martin, J. Am. Chem. Soc. 2010, 132, 17 352-17353. 38
Possible Mechanism
Tobisu, M.; Yamakawa, K.; Shimasaki, T.; Chatani, N. Chem. Commun. 2011, 47, 2946-2948. 39
Effect of Substituents on the Silane Group
R3 Groups Yield (%)
Et3 67
Me2tBu 12
Me2Ph 46
(OEt)3 91
Me(OMe)2 95
Too Bulky,
e- donating
e- donating Literature
Suggested Coordination
Tobisu, M.; Yamakawa, K.; Shimasaki, T.; Chatani, N. Chem. Commun. 2011, 47, 2946-2948. 40
Other Examples in
41 Tobisu, M.; Yamakawa, K.; Shimasaki, T.; Chatani, N. Chem. Commun. 2011, 47, 2946-2948.
• Bulky R Group is disfavor methoxylation
• Reaction is insensitive to position of the OMe Group on polyaromatic ring
Selectivity of Ether Bonds
R Group Conv. (%) Arene (%) Phenol (%)
-H 100 99 99
-CH3 100 96 99
-OCH3 94 88 86
Selectively cleaved at the Aryl Ether Bond
Not -OMe
Sergeev, A. G.; Hartwig, J. F. Science 2011, 332, 439-443.
1 bar = 0.987 atm
42
The Selectivity in Cleavage
R1 Group R2 Group Arene (%) Phenol (%)
- tBu - tBu 72 73
-H -OMe 88 80
-Me -Me 97 99
-H -H 99 99
-CF3 -H 87 99
-CF3 -OMe 87 92
Decrease in
Electron
Donating
Effect
*
*
* Only 10% Ni(COD)2 and 20% SIPr. HCl used.
1 bar = 0.987 atm
Unsymmetrical diaryl ethers were cleaved preferentially at the C-O Bond
adjacent to the more electron-poor aryl ring.
Sergeev, A. G.; Hartwig, J. F. Science 2011, 332, 439-443. 43
Comparison of the Cleaving Group
R Group Arene Alcohol
Methyl 59 Not Quantified
n-Hexyl 85 85
*Phenyl 99 99 (Phenol)
The trend may have be associated with the stability of the anion
The relative reactivity of ether substrates scale:
Ar-OAr >> Ar-OHexyl > Ar-OMe
1 bar = 0.987 atm
Sergeev, A. G.; Hartwig, J. F. Science 2011, 332, 439-443. 44
*Testing substrate was diphenyl ether.
Selectivity Insight of the Cleavage
Sergeev, A. G.; Hartwig, J. F. Science 2011, 332, 439-443. 45
Site B
(Preferred)
Electron Poorer Side
Site A
Products from cleaving
Site A
Products from cleaving
Site B
Did Not Happen:
This methodology is useful, but is limited.
“Temporary Directing Group” strategy does not work in the presence of aromatic ether bond.
Towards a Greener Synthesis
Carbon Based
Chemicals + Fuels Crude Oil
Biomass Cellulose, Lignin,
and Hemicellulose
Breaks
Down
Ni Cat.
Drahl, C. Chopping Up Lignin. Chem. Eng. News, Apr 25, 2011, pp 11.
Distillation
Drawback:
High Ni Cat. Loading
Use of expensive N-Heterocyclic carbene
46
Lignin Representation
Conclusions
Pd and Ni share similar mechanism in Suzuki cross coupling
Nucleophilicity Ni > Pd
Ni can catalyze more functional coupling e.g. aryl sulfamate, aryl
carbamate, and aryl ether.
Ni can be less selective
Oxidative Addition does not depends on BDE
Electron Deficient, Weak C(Aryl) – X Bond, Polyaromatic
Selective Oxidative Addition can be achieved through Guiding
Ni can serve as a viable replacement of Pd, but selectivity
would be an issue.
Ni/ligand loading needs to be reduced
Not too suitable in late state synthesis.
47
Acknowldgement:
o Dr. Jackson
o Dr. Maleczka, Dr. Babak, Dr. Smith
o Dr. Redko
o Anirban, San, Zhenglong, Mahlet, Xianfeng,
Jordan, Michael, Kelsey, Arash, Mark, Katie,
Souful
o You.
48