What Is Grubbs Reaction?
The Grubbs reaction, also known as olefin metathesis, refers to the process in which the carbon-carbon double bonds of olefins are broken under the catalysis of metal carbenes and then recombined to form new olefin molecules.
Catalytic metathesis was observed in the industrial application of olefin polymerization in the 1950s. In 1957, Eleuterio found that propylene could be converted into ethylene and butene by treating it with triisobutylaluminum and molybdenum oxide supported on alumina. In 1966, Natta and his collaborators found that the combination of tungsten hexachloride and triethylaluminum or diethylaluminum chloride could polymerize cycloheptene, cyclooctene and cyclodecene. Calderon believed that the polymerization of cycloolefins into polyene monomers and the disproportionation of alicyclic olefins were the same type of reactions and suggested calling it "olefin metathesis". Due to Grubbs' outstanding contribution in this field, this type of reaction is also called Crubbs reaction.
Fig 1. Grubbs reaction and its mechanism. [1]
Chauvin Mechanism
In 1971, Chauvin proposed a possible mechanism for olefin metathesis, also known as the Chauvin Mechanism. First, the methylene metal (metallocarbene) reacts with olefin to form a metallocyclobutene intermediate. Then, this intermediate is cracked to produce ethylene and a new metallocarbene. One methylene group of the formed ethylene molecule comes from the catalyst, and the other comes from the raw olefin. The new metallocarbene contains a metal with a ligand (represented by M) and an alkylene group from the substrate olefin. This alkylene metal reacts with a new substrate olefin molecule to produce another metallocyclobutene intermediate. In the decomposition of the forward reaction, this intermediate decomposes to produce product and alkylene metal. This alkylene metal enters the next catalytic cycle. Therefore, each step in the catalytic cycle includes alkylene exchange-metathesis. Olefin metathesis is reversible, and the release of ethylene molecules can complete the forward reaction. Product can be a mixture of E and Z isomers.
Grubbs Catalyst
According to the Chauvin mechanism, metal-alkylene complexes can be used as catalysts to achieve olefin metathesis. Scientists have done a lot of work on the design and synthesis of catalysts. In 1990, Schrock reported the most representative molybdenum carbene catalyst (Schrock catalyst). The catalyst is characterized by high catalytic activity and no other additives are required in the reaction system. However, Schrock catalyst is sensitive to oxygen moisture and is not suitable for substrates containing carbonyl and hydroxyl groups.
Fig 2. Structure of Grubbs catalyst. [1]
Since 1992, Grubbs and Hoveyda have reported a series of ruthenium carbene catalysts. These catalysts are not only stable to air, but can also maintain their catalytic activity well even in the presence of water, alcohol or acid. In 1995, Grubbs used tricyclohexylphosphine to replace triphenylphosphine as a ruthenium ligand to synthesize a new generation of ruthenium carbene catalysts with better activity and selectivity (the first-generation Grubbs catalyst). However, the first-generation Grubbs catalyst has a short lifespan, and for some compounds that are difficult to close the ring, the yield is not high when a reasonable amount of catalyst is used.
Subsequently, Crubbs replaced a tricyclohexylphosphine ligand in the first-generation catalyst with a disubstituted dihydroimidazole ligand, and synthesized the "second generation Grubbs catalyst" in 1999. It inherits the stability and wide functional group applicability of Grubbs catalyst and has the same high reactivity as Schrock catalyst. In addition, the ring-closing metathesis reaction of electron-deficient olefin substrates can also reach the preparation level.
Related Products
Application Examples of Grubbs Reaction
- Example 1: A visible light-controlled ruthenium-catalyzed olefin metathesis strategy is reported. The system achieves visible light-controlled metathesis by combining olefin metathesis and photoredox catalysis. [2]
- Example 2: Under mild reaction conditions, a series of chiral pyrrolidine derivatives were directly synthesized through ring-closing enyne metathesis reaction using substrates containing basic or nucleophilic N atoms as raw materials. [3]
Fig 3. Synthetic examples via Grubbs reaction.
References
- Ouellette, R. J., and J. D. Rawn. Organic Chemistry, 2018, 537-559.
- Cédric Theunissen, et al. Am. Chem. Soc. 2019, 141(17), 6791-6796.
- Qian Yang, et al. Organic letters, 2007, 9(5), 769-771.
