recent advances in ni catalyzed suzuki coupling: …€¦ · organic seminar recent advances in ni...

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



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



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



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.;


• 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



An strategic synthesis example:

Seminar Outline

Part 1




Part 2




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


Suggested Di-Oxygen Guided Insertion

Selective Activation is dictated from stability of the T.S.


Coordination Similar to the Ar-Carbamate

(56%)

Seminar Outline

Part 1




Part 2




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


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


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



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)


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




Part 2




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


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


Strategic Synthetic Application


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




Part 2




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


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


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


*Testing substrate was diphenyl ether.

Selectivity Insight of the Cleavage


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

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