Olefin Metathesis Catalysis

1. Olefin Metathesis Catalysis Fan Qi A0048267X GS5002 Journal Club

2. Outline Yves Chauvin Robert H. Grubbs Richard R. Schrock History Mechanism Catalysts Applications

3. Overview on Olefin Metathesis This reaction can be thought of as a reaction where all the C=C bonds are cleaved and then rearranged in a statistical fashion.

4. History R.H. Grubbs, Nobel Lecture, 2005. M. A. Rouhi, C&EN. 2002, 80(51), 34. • 1956 H.S. Eleuterio – DuPont: Ring Opening Reaction observed • 1964 Banks and Bailey – Phillips Petroleum • 1967 Chalderon coined the term “olefin metathesis” • One carbon of a double bond and all its substituents exchanges places with a carbon of another double bond with all of its substituents

5. Mechanism – Initial Work Y. Chauvin, Nobel Lecture, 2005 J. Am. Chem. Soc.,90, 4133 (1968) • Calderon’s Pairwise (conventional) Mechanism • Chauvin’s Metallacyclobutane • Suggested the metal-carbeneintermediate exists

6. Mechanism – Initial Work Predicted Ratio Observed The experiment supports Chauvin’s Mechanism • Grubbs – Deuterium Labeling • Examined ring closing metathesis (RCM)

7. Mechanism – Chauvin’s product  2 reactant  1 Intermediate Metallocycle product  1 reactant  2 Y. Chauvin, Nobel Lecture, 2005 Direct [2+2] cycloaddition of two alkenes is symmetric forbidden. 1970’s Chauvin proposed the widely accepted Mechanism

8. Mechanism – Chauvin’s Makromol. Chem., 141, 161 (1971)

9. Ideal Catalyst C.W. Bielawski, R.H. Grubbs Prog. Polym. Sci. 32 (2007) 1. Produces an infinite amount of product from a single catalyst molecule 100% conversion rate Show high stability to moisture, air, temperature etc. 0 by-products Soluble in organic media Cheap for industrial use

10. Catalyst J. Am. Chem. Soc.,97, 1592 (1975) 1976 – Katz “First” well-defined catalyst Katz suggested that the presence of a carbene on the catalyst would facilitate reactivity

11. Catalyst • 1986 – Grubbs group using Tebbe Reagent • The core metal is Titanium • Isolable metallocyclobutane • catalyzes ROMP of norbornene with good MW control, PDI ~ 1.2 • reactive with heteroatoms L. R. Gilliom and R. H. Grubbs, J. Am. Chem. Soc. 1986, 108, 733.

12. Catalyst R. R. Shrock and Amir H. Hoveyda, ACIE, 2003, 42-38, 4592 • Tungsten Based Catalyst • 1988, Schrock’s Imido-alkoxy • Alkoxides varied to modulate activity • Limited functional group tolerance • 1995, Basset’s Catalyst • Bulky alkoxide ligands show stereoselectivity • Better function group tolerance (acetates, nitriles, anhydrides) • High activity

13. Commercialized Catalysts R.R. Schrock, Nobel Lecture, 2005 • 1990 - Schrock’s Catalyst • Molybdenum alkylidenes • Highly active • Good functional group tolerance • Strict inert conditions, no water • Sterochemical control through chiralalkoxyligands

14. Commercialized Catalysts R.R. Schrock, Nobel Lecture, 2005 • 1992 – 2002 Grubb’s Catalysts • Highly stable • Minimal side reactions • Electron donating lingands • Readily initiated benzylidyne moiety • Increased functional group tolerance (Schrock tolerance + water alcohols, acids)

15. Catalyst Summary Grubb’s 1stGeneration Grubb’s 2ndGeneration Schrock’s Catalyst • Highly reactive • Very stable • Very tolerant • Less expensive • Most reactive • Least stable • Least tolerant • Most expensive • Lest reactive • Moderately stable • Very tolerant • Least expensive

16. Olefin Metathesis Applications R.R. Schrock, Nobel Lecture, 2005 • Wide range of applications • From baseball bat to pharmaceutical agents • Example 1: • Drugs of treating hepatitis C • Example 2: • Polymerization of DCPD

17. Thank you Q & A