Current Litterature october 1 - CCC/UPCMLDccc.chem.pitt.edu/wipf/Current...

1

NNRR

RR

RR

[Ru]Increased Efficiency in Cross-Metathesis Reactions of Sterically Hindered Olefins

Highly Efficient Ruthenium Catalysts for the Formation of Tetrasubstituted

Olefins via Ring-Closing Metathesis

Pushing the Limits of the Metathesis Reaction:

Design of the NHC ligand

Stewart, I. C.; Ung, T.; Pletnev, A. A.; Berlin, J. M.; Grubbs, R. H.; Shrodi, Y. Org. Letters 2007, 9, 1589.

Stewart, I. C.; Douglas, C. J.; Grubbs, R. H. Org. Letters 2008, 10, 441.

And

Dr. Laurent Ferrié10/18/08

Laurent Ferrie @ Wipf Group of 16 10/18/2008

2

Metathesis: Principle

Statistical Distribution of the Olefinic Fragments

From the Greek meta= to change and thesis = position

Calderon et al., J. Am. Chem. Soc. 1968, 90, 4133

[M]


3

Metathesis: Principle

In the Greek mythology:

The griffin = eagle + lion

The hippocampus = horse + fish


4

Metathesis: Catalysts

1931

725 °C

Thermal MetathesisW

CO

CO COCO

COCO

Banks1964

Hetereogenous Catalysis

via W(CO)5=R2

150 °C

CH2

Me

CH2

Me

Me

Me

H2C CH2

Ru

PCy3Ph

Cl

Cl

NN MesMes

Ru

O

Cl

Cl

NN MesMes

Mo

N

i-Pri-Pr

Me

MePhO

O

F3C

F3C

F3C CF3

Ru

PCy3

PCy3Ph

Cl

Cl

Mes =Cy = Cyclohexyl

Shrock CatalystGrubbs Catalyst

2nd generation

Grubbs Catalyst

1st generation

Grubbs-HoveydaCatalyst

1995 1999 20001990

Metathesis Catalysts Used in Organic Chemistry


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Metathesis: Mechanism

Chauvin Y.; Hérisson, J.-L., Makromol. Chem. 1971, 141, 161.

H2C=C H2C=C

M=CR2

C=CH2

M=CR2

M

H2C C

CR2

M

C CH2

CR2

M

CH2

CR2

CR2C=CM=CH2

M

CR2

CH2

C H2C=CR2M=C

++

+

M=CR2

M=CH2

M=C

+

+

H2C=C

H2C=C M=CH2

M=C +

+

H2C=CH2

C=C

2/ Propagation

1/ Initiation


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R1R2+ R2R1

+1) Cross-Metathesis (CM)

2) Ring-Closing Metathesis (RCM) +

3) Polymerizing Metathesisn

+

(ROMP)

(ADMPE)

Metathesis: Application


7

Ring-Closing Metathesis: Limitations

E E

E E

E E

E E

E E

E E

5 mol% catalyst

40°C DCM

Substrate Product

Catalyst: Conversion

Ru

PCy3Ph

Cl

Cl

NN MesMes

Ru

PCy3

PCy3Ph

Cl

Cl

100% 100%

82% 100%

0% 40%

Grubbs et al. Tetrahedron Letters 1999, 40, 2247

E= COOEt

-The obtention of tetrasubstituted olefins by RCM is inefficient

- Phosphine free catalysts (Hoveyda or Grela catalysts) do not give better conversion

Grela, K. and al., J. Am. Chem. Soc. 2004, 126, 9318.


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Overcoming the Limitations: Modification of the NHC ligandMeO2C CO2Me MeO2C CO2Me

5 mol% [Ru]

0.1 M, DCM, 40°C

Ru

O

Cl

Cl

NN

Ru

O

Cl

Cl

NN

Ru

PCy3

Cl

Cl

NN

PhRu

PCy3

Cl

Cl

NN

Ph

tBu

tBuBut

But

Ru

O

Cl

Cl

NNRR

Ru

PCy3

Cl

Cl

NN

Ph

RR

5a (R=Me)5b (R=Et)5c (R=i-Pr)


1

3 4

2



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Overcoming the Limitations: Reaction Monitoring

Ru

O

Cl

Cl

NN

Ru

O

Cl

Cl

NN

Ru

PCy3

Cl

Cl

NN

PhRu

PCy3

Cl

Cl

NN

Ph

tBu

tBuBut

But

Ru

O

Cl

Cl

NNRR

Ru

PCy3

Cl

Cl

NN

Ph

RR



1

3 4

2


5a

6a

1

2

4

3

MeO2C CO2Me MeO2C CO2Me5 mol% [Ru]

0.1 M, DCM, 40°C


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Application to Different Substrates

Ru

O

Cl

Cl

NN

3

Ru

O

Cl

Cl

NNMeMe

6a



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Cross-Metathesis: General Model and Limitations

Grubbs, R. H. et al. J. Am. Chem. Soc. 2003, 125, 11360

Cross-Metathesis:

Type I + Type I: statistic mixture, good yields

Type I + Type II: good yields

Type I + type III: moderate to low yields

Type II + type III: generally low yields


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Cross-Metathesis: Use of Modified NHC Ligands

Ru

O

Cl

Cl

NN

Ru

PCy3

Cl

Cl

NN

Ph

Ru

O

Cl

Cl

NNMeMe

1 2 3



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Cross-Metathesis: Formation of Trisubstituted Olefins by CM


Ru

O

Cl

Cl

NN

Ru

O

Cl

Cl

NNMeMe

2 3


14

[Ru]

NN

R'

[Ru]

NN

R'

R

R

+

R

R

+kB

kD

kA

kC

kA~kB

kC<kD

Productive Metathesis

Unproductive Metathesis


Wagener, K. B. and al. J. Organomet. Chem., 2006, 691, 585.

Productive and Unproductive Metathesis: Mechanistic Aspect


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Ru

O

Cl

Cl

NN

Ru

O

Cl

Cl

NNMeMe

2 3

7

98

7

96

Ru

O

Cl

Cl

NN

PriiPr

PriiPr

7


Improvement in the Formation of Trisubstituted Olefins by

Using Bulky NHC Ligands


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Conclusion

- The design of the NHC ligands in the Ruthenium metathesis catalysts demonstrated

significant improvements to difficult processes in both RCM and CM reactions

- o-Tolyl NHC ligand, by decreasing steric bulk, allows efficient formation of

tetrasubtituted cyclic olefins by RCM.

- o-Tolyl NHC ligand, by decreasing steric bulk, enhances the CM with substituted

terminal olefins but are not effective for the CM with 1,1 disubstituted olefins.

- Bulky NHC ligands, are the most effective for the CM with 1,1 disubstituted olefins

likely due to a selectivity of productive versus unproductive pathways.


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