1IID. MetathesisBoger Notes: p. 355 - 358 (Chapter XZ)II. Special Topics• Introduction• RCM• Cross-Metathesis• ROMPThe Nobel Prize in Chemistry 2005Yves ChauvinInstitut Français du Pétrole, Rueil-Malmaison, France,Robert H. GrubbsCalifornia Institute of Technology (Caltech),Pasadena, CA, USA andRichard R. SchrockMassachusetts Institute of Technology(MIT), Cambridge, MA, USA"for the development of themetathesis method in organicsynthesis".Ring-Closing Metathesis (RCM) and Ring-Opening Metathesis (ROMP)Dr. P. Wipf14/15/20062Important types of metathesis reactions:RCM = ring-closing metathesisROM = ring-openingmetathesisROMP = ring-openingmetathesis polymerizationADMET = acyclic dienemetathesis polymerizationCM = cross-metathesisDr. P. Wipf24/15/20063History of RCM Stille, J. R.; Grubbs, R. H., "Synthesis of (+-)-d9,12-capnellene using titanium reagents." J. Am.Chem. Soc. 1986, 108, 855-856.Nicolaou, K. C.; Bulger, P. G.; Sarlah, D., "Metathesis reactions in total synthesis." Angew.Chem., Int. Ed. 2005, 44, 4490-4527.From the point of view of organic synthesis, the firstnoteworthy, but largely ignored, example of a ring closingdiene metathesis reaction appeared in 1980:History of RCMDr. P. Wipf34/15/20064Important Technical ApplicationsImportant Technical ApplicationsDr. P. Wipf44/15/20065Molybdenum-Based Olefin MetathesisMolybdenum-Based Ring-Closing OlefinMetathesisDr. P. Wipf54/15/20066Molybdenum-Based Ring-Closing OlefinMetathesisXu, Z.; Johannes, C. W.; Salman, S. S.; Hoveyda, A. H. J.Am. Chem. Soc. 1996, 118, 10926.Ruthenium-Based OlefinMetathesisThe synthesis of ruthenium vinylcarbene complexes allowedthe development of well-defined, late transition metal, lowoxidation state complexes that catalyze olefin metathesis.Ruthenium carbene complexes are significantly easier tomake and handle than the Schrock molybdenum complex.In addition to the metathesis of strained cyclic and exocyclicolefins, the remarkable functional group tolerance (alcohols,aldehydes, carboxylic acids) and stability toward air, water,and acid has made this class of compounds particularlyattractive for practical applications (Grubbs, R. H.; Miller, S. J.;Fu, G. C. Acc. Chem. Res. 1995, 28, 446).Dr. P. Wipf64/15/20067Ruthenium-Based OlefinMetathesis: MechanismDias, E. L.; Nguyen, S. T.; Grubbs, R. H. J. Am. Chem. Soc.1997, 119, 3887.Ruthenium-Based Olefin Metathesis:MechanismMechanistically, the major pathway (>95%) was found to involve phosphinedissociation from the metal center, such that a minor associative pathway in whichboth phosphines remain bound can be considered to operate only at higherphosphine concentrations. The formation of the 14-electron metallacyclobutaneintermediate is the rate-determining step. The rate and catalyst activity are directlyproportional to (a) K1, the equilibrium constant for olefin binding, (b) K2, theequilibrium constant for phosphine dissociation, (c) k3, the rate constant formetallacyclobutane formation from the monophosphine olefin complex I2.Dr. P. Wipf74/15/20068Ruthenium-Based Olefin Metathesis:ApplicationsCross-MetathesisChallenges for successful cross-metathesis include:control of olefin geometrysuppression of homodimer formationextending functional group compatibilityDr. P. Wipf84/15/20069Cross-MetathesisChatterjee, A. K.; Morgan, J. P.; Scholl, M.; Grubbs, R. H., "Synthesis offunctionalized olefins by cross and ring-closing metathesis." J. Am. Chem. Soc.2000, 122, 3783.Cross-Metathesis: ApplicationsWipf, P.; Spencer, S. R. "Asymmetric total syntheses of tuberostemonine,didehydrotuberostemonine, and 13-epituberostemonine." J. Am. Chem. Soc. 2005,127, 225-235.Dr. P. Wipf94/15/200610Cross-Metathesis: ApplicationsCross-Metathesis: ApplicationsDr. P. Wipf104/15/200611ROMPROMPDr. P. Wipf114/15/200612• A way of making polymers from cyclic olfins• Condition for prepare living polymers a. monomer is highly strained (irreversible) b. R2 is slow c. organometallic intermediates in the polymerization reaction are stable• Advantages of ROMP a. very narrow molecular weight distribution can be obtained: Mw/Mn approaching 1.0 b. living ROMP catalyst can tolerate a range of functionalities: most catalysts are destroyed in other types of living polymerization reactions c. new materials can be prepared under controlled design conditionsLiving Ring Opening Metathesis Polymerization (ROMP)Brief history• Calderon (1967) : the discovery WCl6/EtAlCl2/EtOH “olefin metathesis”• Grubbs (1986): the first report of living ROMP of a cyclic olefin• Richard R. Schrock (1980’s): molybdenum & tungstencatalystsLiving Polymerizations• Absence of chain termination and chain transfer reaction provides polymers whose molecular weights are precisely predicted and controlled by stoichiometry of polymerization Mn = (g monomer) / (moles of initiator)• Polydispersity will decrease with increasing molecular weight• Synthesis of macromonomers that retain the reactive chain ends when all the monomer has been consumedROMPWakamatsu, H.; Blechert, S. "A new highly efficient ruthenium metathesiscatalyst." Angew. Chem. Int. Ed. 2002, 41, 2403-2405Dr. P. Wipf124/15/200613ROMPWhy Carbene Ligands?The nucleophilic carbenes are ‘phosphine-mimics’ and yetthey are much more. They reside at the upper end of theTolman electronic and steric parameter scales. From solutioncalorimetric studies, it became clear that nucleophiliccarbenes (most of them) are better donors than the bestdonor phosphines.Dr. P. Wipf134/15/200614Why Carbene Ligands?Dr. P.
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