metathesis reactions

1. Metathesis Reactions
Dr. Mishu Singh
Department of Chemistry
M.P.Govt P.G.College, Hardoi
AB + CD AC + BD
1

2. AgNO3 + HCl AgCl + HNO3
NaCN + NH4Cl NaCl + NH4CN
2

3. Metathesis
Metathesis = Meta(Change) + thesis(position)
It is the change of parts of two substances in a chemical reaction
AB + CD AC + BD
or
AD + BC
AgNO3 + HCl AgCl + HNO3
NaCN + NH4Cl NaCl + NH4CN
3

4. Metathesis in an organic reaction entails redistribution of
alkenes/ alkynes fragments by the scission of carbon - carbon
double/ triple bonds. Two  and two  bonds are broken and
two new  and two new  bonds are formed.
4

5. Olefin metathesis was first observed in the 1950s (Herbert S.
Eleuterio, at Du Pont's petrochemicals department) ,
The reaction was extended with cyclopentene
They tell "the polymer we got looked like somebody took a pair of
scissors, opened up cyclopentene, and neatly sewed it up again"
However real mechanism of these reaction remained the mystery till
1990.
Discovery of olefin Metathesis
polymer
5

6. Olefin metathesis is an equilibrium process and with many
alkenes, substrates yields a mixture of starting material and two
or more alkenes products.
 However, with terminal alkenes, one metathesis product is
ethylene gas (CH2=CH2), which escapes from the reaction
mixture and drives the equilibrium to the right.
Thus, monosubstituted alkenes (RCH=CH2) and 2,2-
disubstituted alkenes (R2C=CH2) are excellent metathesis
substrates because high yields of a single alkene product.
Characteristics of Metathesis Reactions
6

7. Some Important Metathesis Reactions
1. Alkene Metathesis
2. Alkyne Metathesis
3. Enyne- Metathesis
7

8. Transalkylidination or Transalkylation ?
At first, it was questioned , whether, olefin metathesis is exchange of
alkyl or alkylidene groups.
Which one is correct? 8

9. Experimental proof for Transalkylidination
9

10. Fundamental Olefin Metathesis Reactions
10

11. It is called as CM
1.Cross-metathesis:
11

12. 2. Ring-closing metathesis
Two double bonds must be in same compound.
Ring formation ( cyclization ) occurs rapidly.
12

13. 3. Ring-Opening Metathesis Polymerization
Ru
C
RuC
RuC
n
n
metathesis
metatheses
13

14. 4. Acyclic Diene Metathesis polymerization
+
+
C8 C8
C14 C2
Carrying this reaction out over and over with the more reactive
terminal double bonds leads to acyclic diene metathesis (ADMET)
polymerization with longer chain diene substrates.
Ru
C
14

15. The Catalysts
Benzylidenebis(tricyclohexylphosphine)
dichlororuthenium [1,3-bis-(2,4,6-trimethylphenyl)-2-
imidazolidinylidene]dichloro(phenylmeth
ylene)(tricyclohexylphosphine)ruthenium
2,6-Diisopropylphenylimidoneophylidene
molybdenum(VI) bis(hexafluoro-t-butoxide)
These are called carbene
complex, metallocarbene
or alkylidene complex
15

16. Commercially available, as is synthetic precursor.
Must be handled under argon or nitrogen using
dry conditions.
Relatively intolerant of proton on heteroatoms.
Tolerant of S, P and nitrile functional groups.
High reactive.
 Electron deficient Mo(VI), 14 electron species.
 N Ar ligand, OR ligand and initial alkylidine
need to be bulky.
 Electron withdrawing alkoxides increase
electrophilicity of metal center, hence increases
reactivity.
Schrock’s catalyst
16

17. Reasonably stable toward water, oxygen and
minor impurities ------ ease of handling.
Lower activity vs. Mo and imido alkylidene
catalyst.
High functional group tolerance.
Halides: catalyst activity I < Br < Cl.
Ru catalyst containing N-heterocyclic
imidazol-2- ylidene , Carbene.
Activity is significantly higher then
parent Ru complex.
Grubbs Catalyst
17

18. 1. Dr. Yves Chauvin at the Institute Francisdupetrole, France
2. Prof. Robert H. Grubbs, California Institute of Technology USA
3. Prof. Richard R. Schrock, Massachusetts institute of Technology,
Cambridge USA
The Nobel Prize In Chemistry 2005
For The Development Of Metathesis
Method In Organic Synthesis
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19. 2005 Nobel Prize for Metathesis
19

20. Explanation of the mechanism
Wrong Turns
20

21. Chauvin’s Mechanism
21

22. 22

23. Alkynes Metathesis
23

24. Alkynes Metathesis Mechanism
24

25. Enyne metathesis
25
The Enyne metathesis is a ruthenium-catalyzed bond reorganization
reaction between alkynes and alkenes to produce 1, 3-dienes.
Alkyledine migration from the alkene to alkyne carbon. The
driving force thermodynamically stable 1,3-diene.
Catalyst
When the reaction is intramolecular, called as Ring Closure
Enyne Metatesis RCEM

26. Mechanism Of Enyne Metathesis
This is the proposed "yne-then-ene" mechanism.The driving force for
the reaction is the formation of thermodynamically stable conjugated
butadiene 26

27. Enyne metathesis mechanism
Initiation :
Catalytic Cycle :
27

28. Metathesis in Chemistry
Metathesis
Applications
28

29. Application Of Metathesis In Synthesis Of
Biologically Active Compounds
Highly functionalised novel bicyclic β-lactams
synthesis
These bicyclic β-lactams systems have been prepared via the enyne
metathesis reaction using catalytic quantities of trans (Cy3P)2Cl2Ru=CHPh
(Cy = Cyclohexyl)
29
Chem. Comm.1997, 1375

30. Complex Heterocyclic lactam
Fused bicyclic lactams having quinolizidine alkaloid skeletons are
commonly observed structural unit of many important compound
which display a broad rang of biological activity.
30
J. Org. Chem. 2004, 69, 6305

31. Balanol
 It shows remarkable anticancer activity.
 Also used against HIV infection, Rheumatoid Arthritis,
cardiovascular disorder, CNS dysfunction.
31

32. Formal Total Synthesis of Balanol
A.Furstner, J. Org. Chem. 2000, 65, 1738
32

33. Turrianes
 Turrianes are efficient DNA –cleaving agents under oxidative condition
in presence of copper ion and butyl amine.
These are naturally occurring cyclophanes and consist of aromatic unit
specially benzene and an aliphatic chain that form chain bridge between
benzene ring.
33

34. Sphorolipid lactone
 They are natural products
 Sphorolipid derivatives have antibacterial
and antifungal activity.
 Present study documents in –vitro
 spermicidal and anti -HIV virucidal activities against human
semen are similar to commercial spermicidal Nonoxynol-9 (N-9).
34

35. Partial Synthesis of Sphorolipid lactone
Furstner, J.Org. Chem. 2000, 65, 8758
35

36. Dehydrohomoancepsenolide
 Butenolide is natural product incampas a broad spectrum of
antibacterial, antimalarial, antitumor and herbicidal activity.
Dehydrohomoancepsenolide is a natural product.
36

37. Org. Lett. 2000, 2,2463
Synthesis of Dehydrohomoancepsenolide
37

38. BILN- 2061
 BILN- 2061 is a new chemical entity
which shows promising results against
the Hepatitis C virus by inhibiting
Seine Protease of HCV.
38
 BILN- 2061 developed by Boehringer-Ingelheim.
 BILN- 2061is in Phase II Clinical trial in US and Europe.
 BILN 2061, 15-membered macro cyclic compound containing
a (Z)- olefin.

39. Synthesis of BILN-2061
Org. Lett., 2004,6,2901-2904
39

40. Synthesis of ORL Pheromones
The omnivorous leaf roler (OLR) is a pest of appels, pears, peaches,
and nectarines.
The OLR pheromone is an 82:18 ratio of E to Z-tetradecenyl acetate
isomers. The C M metathesis reaction, using the second generation
Grubbs`catalyst, produces the desired isomeric ratio.
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41. MISCELLANEOUS
Macrocyclisation
 Upto 30 membered ring can be synthesized
 Cis and trans isomers are formed
 Higher temperature generally required
41

42. Cyclo oligomerisation by Alkyn metathesis
Synlett 2003,29 & Synthesis,2003,2535
42

43. CIVETONE
It is one of the important valuable fragrance containing
compounds used in perfume industry, chemically macrocyclic
ketone.
Stereoslective synthesis of Civetone
Chem. comm. 2005, 2307-2320 43

44. Synthesis Of Phenanthrene
Conversion of biphenyl to phenanthrene
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45. Synthesis of Cyclophanes
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46. Multicomponent, Tandem metathesis/Diel’s -Alder
Cycloaddition
Synthesis of heterocycle with multistereocenter
Reaction Sequences
Org.lett. 2003, 5, 3439
46

47. Dendrimer a family of nano-sized, 3D polymer , a class of
macromolecules having highly branched architecture The name comes
from the Greek word δένδρον (dendron), which translates to "tree
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48.  The examples mentioned above illustrate the broad applications of
metathesis reactions for the synthesis of several drugs and many
other valuable chemical compounds. Thus this reaction has great
significance for both academic research and industry for
development of commercially valuable compounds.
 The beauty of metathesis method is that it take shorter synthetic rout
give higher yield, fewer by-products and it tolerates different
functional groups, present in starting material.
 Thus metathesis chemistry has opened up novel opportunity to
explore the enormous diversity of organic molecules and contribute
to a green chemistry.
Conclusions
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49. Drawing the Products of Alkene Metathesis
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50. Exercises
Give the major product of the following reactions
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