1、Chapter 12Alkene Metathesis,Alkene metathesis is the metal-catalyzed disproportion of alkenes. This reaction has been known for nearly 50 years, but only in the past decade has it become widely used in both industrial and academic labs for the synthesis of polymers and complex organic compounds. The
2、 2005 Nobel prize was award to Yves Chauvin, Richard Schrock, and Robert Grubbs for their work in developing olefin metathesis into a widely used process.,There are several classes of olefin metathesis reactions.,All of the above reactions are reversible, so equilibrium mixtures are obtained. To pro
3、duce high yields of a given product a suitable driving force must be present. Cross metathesis: Mixtures of products are produced unless a volatile byproduct (ethylene) is produced that can be removed from the reaction mixture. RCM is favored for the production of unstrained rings and is driven both
4、 entropically and by the elimination of a volatile alkene. ROM is only favored at very high olefin concentrations, or more commonly with strained olefins.,Olefin metathesis was discovered in the 1950s about the same time as Ziegler-Natta olefin polymerization. The catalysts used from this time throu
5、gh the 80s were poorly defined combinations of a metal salt and main-group organometallic species. (i.e., WCl5/Bu4Sn or MoCl2(NO)2(PPh3)2/Al2Me3Cl3. These types of catalysts are still used industrially.,Metathesis in the Shell Higher Olefin Process (SHOP),cat,Mechanism:,The mechanism of the reaction
6、 was disputed for a long time. One of the early proposals by Chauvin turned out to be correct, but was not accepted for some time.,His early contribution was the reason he was awarded the Nobel prize.,J. Am. Chem. Soc., 1976, 98, 2519,Well-defined catalysts,With the acceptance of the Chauvin mechani
7、sm, metal-carbene complexes were explored for their ability to catalyze olefin metathesis.,The first active, well-defined system was (OC)5W=CPh2 (Tetr. Lett., 1976, 17, 4247). This complex would polymerize cyclic olefins with modest activity and high selectivity for cis-alkene polymers.,Today there
8、are two major classes of metathesis catalysts that are widely used. A molybdenum carbene developed by Schrock (Tetrahedron, 1999, 55, 8141-8153) and a ruthenium carbene developed by Grubbs (Acc. Chem. Res., 2001, 34, 18-29). Both compounds are now commercially available and have been applied to a wi
9、de range of synthetic problems.,The Schrock metathesis catalystSynthesis:,The molybdenum carbene is very sensitive to oxygen and moisture as well as protic compounds (alcohols, ketones, aldehydes, etc.), but is stable for long periods in an inert atmosphere.,Reactivity and mechanism:The Schrock meta
10、thesis catalysts carry out the living ring opening metathesis polymerization of cyclic olefins.,Electron withdrawing alkoxide groups give higher reaction rates in metathesis reactions. The t-BuO complex forms stable metallacycles that only slowly decompose to give the ring opened product.,Asymmetric
11、 Ring Closing MetathesisSchrock in collaboration with Hoveyda have applied the molybdenum alkylidenes to asymmetric synthesis (Chem. Eur. J., 2001, 7, 945-950). By replacing the alkoxide ligands with chiral diols, enantioselectiveRCM reactions are possible. This methodology can be applied to the res
12、olution of racemic dienes or enantioselective ring closing of meso-dienes.,C6H6, r.t.,Advantages of the Schrock catalyst: Very high activity Allows synthesis of tri- and tetra-substituted alkenes Efficient asymmetric ring closing metathesis.,Disadvantages of the Schrock catalyst: Requires rigorous e
13、xclusion of air and moisture Limited functional group tolerance,The Grubbs Metathesis Catalyst,The Schrock catalyst and related complexes based on electrophilic metal centers suffered from limited tolerance of functional groups. While the Schrock catalyst would tolerate ketones, esters, and amides,
14、function groups such as aldehydes, alcohols, and acids were not tolerated, nor was water. It would be expected that lower-valent , late transition metal complexes would be more tolerant of electrophilic and protic functional groups. This is because the carbene would be less nucleophilic (more Fische
15、r character).,Grubbs has developed an excellent family of catalysts based on Ru alkylidienes (Acc. Chem. Res. 2001, 34, 18-29).,Synthesis:The synthesis of the first generation catalyst occurs in high yield and has been carried out in 10 kg batches.,Reactivity and Mechanism:The Grubbs catalyst carrie
16、s out living ROMP polymerization similar to the Schrock catalyst, but with lower activity. The Grubbs catalyst shows improved functional group compatibility, though. In fact, aqueous phase ROMP polymerizations are possible with water-soluble versions of the Grubbs catalyst.,The Grubbs catalyst has b
17、een most widely used in organic synthesis for RCM and CM reactions, due to its stability and good functional group compatibility.,RCM (J. Am. Chem. Soc., 1997, 119, 2733),Heterocross Metathesis (J. Am. Chem. Soc., 2000, 122, 58-71),There are several pieces of data suggesting that phosphine dissociat
18、ion is required for metalacycle formation. (J. Am. Chem. Soc. 1997, 119, 3887) (J. Am. Chem. Soc, 1997, 119, 7157),B,A,The activity of the Grubbs system is dependent on both the phosphine and the halide ligands.Larger more electron donating phosphines give higher ratesSmaller less electron donating
19、halides give higher rates.,L = Cl Br I R3P = PCy3 P(i-Pr)3 PhPCy2 PhP(i-Pr)2,Design of the next generation of Grubbs catalystsThe mechanistic results suggested that the active species was a monophosphine ruthenium alkylidene. Therefore, stable monophosphine complexes were sought. The ideal catalyst
20、would have high activity and stability. This requires easy formation of the 14 electron monophosphine complex without decomposition.,High activity, but unstable,Stable, but low activity,Low activity,High actvity and StabilityGrubbs 2,Hoveyda Catalyst High activity Potentially recyclable Slower initi
21、ation than Grubbs 2,The monocarbene complex and the saturated carbene analog allow reactions that were previously only possible with the Schrock catalyst.,Alkyne MetathesisAlthough alkene methathesis is well established as a synthetic methodology, particularly with the Grubbs catalysts, the analogous alkyne metathesis is much less well developed.,
