15.09.03 · orgchem / organometallic-synthesis

Olefin metathesis: Grubbs catalyst, ring-closing, and cross metathesis

stub3 tiersLean: nonepending prereqs

Anchor (Master): Grubbs — Handbook of Metathesis, Vol. 1–3 (Wiley-VCH, 2003)

Intuition Beginner

Olefin metathesis is a reaction that swaps the groups attached to two carbon-carbon double bonds. Imagine cutting each double bond in half and then rejoining the pieces differently. Two molecules, each with a double bond, exchange partners to give two new molecules with new double bonds. A metal catalyst makes this swap happen without being consumed.

The most important application is ring-closing metathesis (RCM). When a single molecule has two double bonds separated by a chain of carbon atoms, metathesis can join the two ends together to form a ring. This is one of the most powerful ways to make medium and large rings in organic chemistry. Cross metathesis (CM) does the same swap between two separate molecules, installing a new double bond where the two fragments join.

Robert Grubbs developed ruthenium catalysts that made olefin metathesis practical for ordinary laboratory synthesis. These catalysts tolerate air, moisture, and most functional groups, which is unusual for organometallic reagents. The 2005 Nobel Prize in Chemistry was awarded to Yves Chauvin, Robert Grubbs, and Richard Schrock for the development of the olefin metathesis reaction.

Visual Beginner

The metal catalyst (Ru) carries a carbene group. It reacts with one double bond to form a four-membered ring intermediate, which breaks apart to give a new metal carbene and a new alkene. This cycle repeats, shuffling the double-bond partners until the most stable product is formed.

Worked example Beginner

Problem: Use ring-closing metathesis to form a six-membered ring from a diene substrate.

Solution:

Start with a linear molecule that has two terminal double bonds separated by a chain of four carbon atoms. The chain length determines the ring size: four carbons between the two double bonds gives a six-membered ring upon closure.

Add Grubbs 2nd generation catalyst (5 mol%) in dichloromethane at room temperature. The catalyst reacts with one terminal double bond to form a metal carbene, then that carbene attacks the second double bond. The two ends join to form cyclohexene, and ethylene gas (CH2=CH2) is released as the byproduct. The release of ethylene gas drives the reaction forward — it bubbles out of solution, preventing the reverse reaction. This thermodynamic driving force is why RCM works so well for terminal alkenes.

Check your understanding Beginner

Formal definition Intermediate+

Chauvin mechanism

The mechanism of olefin metathesis was proposed by Yves Chauvin in 1971. The key insight is that the reaction proceeds through a metal carbene (alkylidene) intermediate and a series of [2+2] cycloaddition and cycloreversion steps:

Initiation. The precatalyst (e.g., a Grubbs catalyst) loses a ligand (typically a phosphine) to generate the active 14-electron ruthenium alkylidene species.
[2+2] Cycloaddition. The Ru=C double bond of the metal carbene undergoes a [2+2] cycloaddition with the C=C double bond of the substrate, forming a metallacyclobutane intermediate.
Cycloreversion. The metallacyclobutane undergoes retro-[2+2] cycloaddition, but breaking different bonds than those that formed. This produces a new alkene and a new metal carbene.

This cycle repeats, with the new metal carbene reacting with another substrate alkene. The net result is the exchange of alkylidene fragments between two alkenes. Chauvin's key contribution was recognizing that the metal carbene is both a reactant and a product — it is regenerated in each turnover, making the process catalytic in metal.

Grubbs catalysts

The Grubbs catalyst family made olefin metathesis practical for synthetic organic chemistry:

Grubbs 1st generation (G1): RuCl2(PCy3)2(=CHPh). Two tricyclohexylphosphine ligands, one benzylidene carbene, and two chlorides. The benzylidene is the initiating carbene. One PCy3 dissociates to generate the active 14-electron species. G1 is air-stable, tolerant of many functional groups, and commercially available. It is the most general-purpose metathesis catalyst but has relatively slow initiation and limited activity with sterically demanding substrates.
Grubbs 2nd generation (G2): RuCl2(PCy3)(IMes)(=CHPh). One PCy3 is replaced by an N-heterocyclic carbene (NHC) ligand (IMes = 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene). The NHC is a strong sigma donor with minimal pi-acceptor ability, which increases the electron density at Ru and accelerates the [2+2] cycloaddition step. G2 is more active than G1 for sterically hindered and electron-poor substrates, and it enables metathesis of trisubstituted alkenes.
Hoveyda-Grubbs catalyst: RuCl2(IMes)(=CH(2-OiPrC6H4)). The benzylidene carries an isopropoxy group that chelates to Ru through oxygen. The chelate stabilizes the precatalyst and the catalyst is activated by dissociation of the isopropoxy group. This catalyst is more stable toward air and moisture than G1 or G2, and it can be recovered and recycled. The Hoveyda-Grubbs 2nd generation catalyst (with the NHC ligand) is one of the most widely used metathesis catalysts.

Thermodynamic driving force

Olefin metathesis is formally reversible — the position of equilibrium is determined by the relative stability of the starting materials and products. Several factors drive the reaction forward:

Ethylene loss (RCM and CM). When terminal alkenes react, ethylene is produced as a byproduct. Because ethylene is a gas, it escapes from the reaction mixture, removing product from equilibrium and driving the reaction to completion. This is the primary driving force for RCM and many CM reactions.
Ring strain (ring-opening metathesis). In ring-opening metathesis polymerization (ROMP), relief of ring strain in the starting cyclic alkene drives the reaction forward. Cyclobutene, norbornene, and cyclooctene are excellent ROMP monomers because of their high ring strain.
Conjugation and stability. Formation of a more substituted or conjugated alkene can provide a thermodynamic driving force. Cross metathesis that produces a trans-disubstituted alkene from two terminal alkenes is favorable because the trans-disubstituted product is more stable than the terminal alkene starting materials.

Substrate scope and selectivity

Olefin metathesis works with a broad range of alkene types, but the reactivity depends on substitution pattern:

Terminal alkenes are the most reactive substrates for RCM and CM.
1,1-Disubstituted alkenes (gem-disubstituted) are less reactive but can participate in RCM to form quaternary centers.
Trans-disubstituted alkenes are less reactive than terminal alkenes.
Trisubstituted alkenes require the more active G2 or Hoveyda-Grubbs catalysts.
Tetrasubstituted alkenes are formed only with the most active catalyst systems and with difficulty.

Cross metathesis selectivity follows the "A-value" classification developed by Grubbs: Type I alkenes (terminal, reactive) homodimerize rapidly; Type II alkenes (1,1-disubstituted, less reactive) homodimerize slowly; Type III alkenes (cis- and trans-disubstituted) do not homodimerize. Productive cross metathesis is most efficient between alkenes of different types, or between two Type I alkenes when one partner is used in excess.

Key results

Ring-closing metathesis for macrocycles. RCM is one of the few reliable methods for constructing medium and large rings (8-membered and above). The reaction benefits from high dilution conditions (typically 0.001-0.01 M) to favor intramolecular cyclization over intermolecular oligomerization. RCM has been used to construct 12- to 16-membered macrolide rings in total synthesis.
Cross metathesis for fragment coupling. CM provides a direct method for joining two molecular fragments through a new C=C bond. Unlike cross-coupling reactions (Suzuki, Heck), CM does not require pre-functionalization with halides or boronic acids — only terminal or internal alkenes. The tradeoff is that E/Z selectivity is often moderate, and homodimerization of each partner competes with the desired cross product.
Enyne metathesis. The reaction of an alkene with an alkyne produces a 1,3-diene. The metallacyclobutane intermediate from the alkene reacts with the alkyne, expanding to a metallacyclopentadiene that undergoes cycloreversion. This provides a unique route to conjugated dienes that cannot be accessed by simple alkene metathesis.
Ring-opening metathesis polymerization (ROMP). Strained cyclic alkenes undergo ring-opening polymerization catalyzed by metal alkylidenes. The release of ring strain drives the polymerization. ROMP produces polymers with precise stereochemistry and narrow molecular weight distributions when living catalysts (e.g., Schrock molybdenum alkylidenes) are used.

Exercises Intermediate+

Exercise 1 (easy, short-answer).

Draw the Chauvin mechanism for the cross metathesis of two molecules of propene (CH2=CHMe) to give ethylene and 2-butene. Show the metal carbene, the metallacyclobutane intermediate, and the product metal carbene at each step.

Hint

Start with a metal methylidene (Ru=CH2) reacting with propene. The [2+2] gives a metallacyclobutane with methyl and hydrogen substituents. Cycloreversion breaks the opposite bonds to give a new metal carbene and a new alkene.

Answer

Step 1: Ru=CH2 + CH2=CHCH3 undergo [2+2] cycloaddition to form a metallacyclobutane (Ru-CH2-CH2-CH(CH3)-Ru ring).

Step 2: Cycloreversion breaks the Ru-C bonds opposite to those formed, giving Ru=CHCH3 (a metal propylidene) and CH2=CH2 (ethylene).

Step 3: Ru=CHCH3 + CH2=CHCH3 undergo [2+2] cycloaddition to form a new metallacyclobutane.

Step 4: Cycloreversion gives Ru=CH2 (regenerating the original methylidene) and CH3CH=CHCH3 (2-butene).

The net reaction: 2 CH2=CHCH3 → CH2=CH2 + CH3CH=CHCH3.

Exercise 2 (medium, short-answer).

Compare Grubbs 1st and 2nd generation catalysts. Why does replacing one PCy3 with an NHC ligand increase catalytic activity? Discuss the effect on initiation rate, propagation rate, and substrate scope.

Hint

Consider the electronic and steric differences between PCy3 and an NHC ligand. How do these affect the electron density at Ru, the stability of the active 14-electron species, and the rate of [2+2] cycloaddition?

Answer

The NHC ligand in G2 is a stronger sigma donor than PCy3, increasing electron density at Ru. This has several consequences:

Initiation: G1 initiates by dissociation of one PCy3 from RuCl2(PCy3)2(=CHPh). G2 initiates by dissociation of the single PCy3 from RuCl2(PCy3)(NHC)(=CHPh). Because the NHC is a stronger donor and less labile than PCy3, G2 has a more accessible coordination site after PCy3 dissociation.

Propagation: The 14-electron active species RuCl2(NHC)(=CHR) in G2 is more electron-rich than the analogous RuCl2(PCy3)(=CHR) in G1. The increased electron density accelerates the [2+2] cycloaddition step (the rate-determining step in most cases), because the metal carbene is a better nucleophile toward the electrophilic alkene.

Substrate scope: G2 handles sterically demanding substrates (trisubstituted alkenes, 1,1-disubstituted alkenes in RCM) that G1 cannot efficiently process. The NHC also stabilizes the catalyst against decomposition pathways. However, G1 is sometimes preferred when selectivity is important: the slower propagation rate can provide better control over product distribution, and G1 is less likely to promote unwanted side reactions with sensitive functional groups.

Exercise 3 (medium, short-answer).

A diene with two terminal alkenes separated by 10 carbon atoms is subjected to RCM using Grubbs 2nd generation catalyst at 0.01 M concentration. The major product is a 12-membered ring. Explain why high dilution is necessary and what would happen at higher concentrations.

Hint

Consider the competition between intramolecular cyclization (ring-closing) and intermolecular reaction (oligomerization). How does concentration affect the relative rates of these two processes?

Answer

High dilution favors intramolecular cyclization over intermolecular oligomerization. The rate of intramolecular RCM is first-order in substrate concentration (the two alkene ends are tethered within the same molecule), while the rate of intermolecular oligomerization is second-order in substrate concentration (two different molecules must collide). At high dilution (0.001-0.01 M), the first-order intramolecular pathway dominates. At higher concentrations, the second-order intermolecular pathway becomes competitive, leading to dimeric, trimeric, and higher oligomeric products. The competition is especially significant for large rings (12-membered and above), which have unfavorable cyclization kinetics due to the low effective molarity of the chain ends. Medium rings (8-11 members) also require high dilution because of their conformational strain. For 5- and 6-membered rings, the intramolecular pathway is so fast that higher concentrations can be tolerated.

Exercise 4 (hard, short-answer).

Design a synthetic route to the macrocyclic natural product (+)-dactylolide using ring-closing metathesis as the key step. Consider: (a) which double bond to form by RCM, (b) which catalyst to use, and (c) whether E/Z selectivity is a concern. Describe how the choice of ring size and substitution pattern affects the RCM outcome.

Hint

Dactylolide contains a macrolactone with a trans double bond in the ring. Consider whether RCM at the double bond site or at a different position is more practical. The macrocyclic ring is large enough that high dilution will be required. Z-selective catalysts were not available when the original synthesis was performed — consider how this constrains the strategy.

Answer

For a macrocyclic RCM approach to dactylolide, the disconnection is made at the trans double bond in the macrolactone ring, giving a linear seco-acid precursor with two terminal alkenes at the appropriate positions.

(a) The RCM should form the C=C bond within the macrocycle. The two terminal alkene partners are positioned such that cyclization gives the desired ring size (typically 12-16 atoms in the ring). The trans geometry of the product is the thermodynamically favored isomer under standard RCM conditions.

(b) Grubbs 2nd generation or Hoveyda-Grubbs 2nd generation catalyst is preferred for macrocyclic RCM because of the higher activity needed to close large rings at the low concentrations required (0.001-0.005 M). The Hoveyda-Grubbs variant is advantageous because its slower initiation rate provides a steady-state concentration of active catalyst that matches the slow rate of macrocyclization.

(c) E/Z selectivity is a nontrivial concern. Standard Grubbs catalysts produce predominantly the E (trans) alkene for large rings, which is the desired geometry for dactylolide. However, the selectivity is moderate (typically 3:1 to 10:1 E) and the Z isomer must be separated. Modern Z-selective catalysts (e.g., Schrock's molybdenum catalyst with biphenolate ligands, Grubbs' ruthenium catalysts with chelating dithiolate ligands) could in principle be used if the Z isomer were desired, but for dactylolide the E-selectivity of standard catalysts is advantageous. The ring size affects RCM outcome because large rings (12+ members) have low effective molarity, requiring careful optimization of concentration, temperature, and catalyst loading to achieve acceptable yields.

Olefin metathesis: advanced catalysts, selectivity, and applications Master

Schrock molybdenum catalysts

Richard Schrock developed high-oxidation-state molybdenum alkylidene catalysts that predated the Grubbs ruthenium systems. The Schrock catalyst Mo(NAr)(CHCMe2Ph)(OCMe(CF3)2)2 (where Ar = 2,6-diisopropylphenyl) is significantly more active than any ruthenium catalyst, enabling metathesis of sterically demanding and electronically deactivated substrates including tetrasubstituted alkenes.

The high activity of the Schrock catalyst arises from the electrophilic nature of the Mo(VI) center. The alkoxide ligands (OCMe(CF3)2) are strongly electron-withdrawing, making the Mo=C bond highly electrophilic and promoting [2+2] cycloaddition with electron-rich alkenes. The imido ligand (NAr) provides steric protection and prevents decomposition.

The Schrock catalyst's limitations are practical: it is extremely air- and moisture-sensitive (requiring glovebox handling), incompatible with many functional groups (protic functional groups, aldehydes, and some heterocycles decompose the catalyst), and expensive to prepare. These limitations drove the development of the more robust ruthenium catalysts by Grubbs. However, the Schrock catalyst remains indispensable for substrates that require the highest metathesis activity.

Z-Selective metathesis

Controlling E/Z selectivity in olefin metathesis has been a major challenge. Standard Grubbs and Schrock catalysts produce predominantly E alkenes because the E isomer is thermodynamically more stable. Achieving Z selectivity requires kinetic control — the catalyst must favor formation of the Z product regardless of thermodynamic preferences.

Three approaches to Z-selective metathesis have been developed:

Schrock Mo catalysts with stereogenic-at-metal centers. Molybdenum catalysts with biphenolate or binaphtholate ligands produce Z alkenes with high selectivity (>95:5 Z). The selectivity arises from the chiral environment at Mo, which directs the approach of the substrate alkene to one face of the metallacyclobutane intermediate. The Z product is formed from the syn-substituted metallacyclobutane, which is favored by the ligand geometry.
Grubbs Ru catalysts with chelating dithiolate ligands. Ruthenium catalysts of the type RuCl2(L)(=CHAr)(S2C6H2-2,4,6-R3) where L is an NHC or phosphine, produce Z alkenes in cross metathesis and ring-closing metathesis. The dithiolate ligand enforces a geometry at Ru that preferentially forms the syn-metallacyclobutane leading to the Z product.
Tungsten catalysts. Tungsten-based catalysts developed by Schrock and Hoveyda achieve Z selectivity in CM and RCM with turnover numbers comparable to the Mo systems.

Z-Selective metathesis has transformed the synthesis of natural products and pharmaceuticals that contain Z alkenes (e.g., the anticancer agent discodermolide, various insect pheromones). Before Z-selective catalysts, Z alkenes had to be installed by non-metathesis methods (Wittig reaction with stabilized ylides, partial hydrogenation of alkynes) or by stereospecific transformations.

Relay metathesis

Relay metathesis is a strategy for achieving site-selective ring-closing metathesis in polyene substrates. In a relay metathesis reaction, a temporary tether (typically an allyl or vinyl alcohol) is appended to the substrate. The catalyst initiates at the relay site rather than at one of the substrate alkenes, and the metal alkylidene migrates through a defined sequence of [2+2]/cycloreversion steps until it reaches the desired ring-closing site.

The advantage of relay metathesis is control over regioselectivity. In a substrate with multiple alkenes, the Grubbs catalyst may initiate at any accessible terminal alkene, giving mixtures of ring sizes. The relay group directs initiation to a specific site, ensuring that only the desired ring is formed. This strategy has been applied to the synthesis of complex polycyclic natural products where multiple RCM pathways are possible.

Enyne metathesis

Enyne metathesis couples an alkene with an alkyne to produce a 1,3-diene. The mechanism differs from alkene-alkene metathesis: the metallacyclobutane from the initial [2+2] cycloaddition with the alkene reacts with the alkyne, expanding to a metallacyclopentadiene (a five-membered ring containing Ru and four carbons). Retro-[2+2] of the metallacyclopentadiene produces the 1,3-diene and regenerates the metal carbene.

Two modes of enyne metathesis are recognized: ring-closing enyne metathesis, where the alkene and alkyne are tethered within the same molecule, producing a cyclic 1,3-diene; and cross enyne metathesis, where separate alkene and alkyne molecules react. Ring-closing enyne metathesis is a powerful method for constructing diene-containing rings, and the cyclic diene product can undergo subsequent Diels-Alder reactions, providing a tandem metathesis/Diels-Alder strategy for polycyclic molecule synthesis.

Macrocyclic RCM and total synthesis

Ring-closing metathesis has become the method of choice for constructing macrocyclic rings (12-membered and above) in natural product synthesis. Key considerations for macrocyclic RCM include:

High dilution. Concentrations of 0.001-0.01 M are required to suppress intermolecular oligomerization.
Catalyst choice. Hoveyda-Grubbs 2nd generation is preferred because its slower initiation rate avoids buildup of active catalyst that would promote oligomerization. For the most challenging substrates, the more active Schrock Mo catalyst may be required.
Conformational preorganization. The efficiency of macrocyclic RCM depends on the substrate's ability to adopt a conformation that brings the two alkene termini into proximity. Substrates with conformational constraints (intramolecular hydrogen bonds, steric gearing, or pre-existing rings) cyclize more efficiently than flexible chains.
E/Z selectivity. Standard catalysts give predominantly E alkenes in large rings. When the natural product contains a Z alkene, Z-selective catalysts or alternative strategies (alkyne RCM followed by partial hydrogenation, or a non-metathesis disconnection) must be employed.

Landmark applications include the synthesis of epothilone analogs (Danishefsky, Nicolaou), diplamide E (Fürstner), and various macrocyclic protease inhibitors in pharmaceutical chemistry.

Industrial applications

Olefin metathesis has significant industrial applications beyond academic synthesis:

Petrochemical industry. The Olefins Conversion Technology (OCT) process uses WO3/SiO2 catalysts to cross-metathesize ethylene and 2-butene to produce propylene, addressing the global propylene supply-demand imbalance. This process operates at 300-400 degrees C and is one of the largest-scale applications of heterogeneous metathesis catalysis.
Polymer production. Ring-opening metathesis polymerization (ROMP) produces specialty polymers including polynorbornene (used in rubber and elastomer applications), polydicyclopentadiene (used in reaction injection molding for automotive and industrial components), and hydrogenated polyalkenamers (saturated polymers with properties similar to natural rubber).
Pharmaceutical synthesis. RCM is used as a key step in the synthesis of several drug candidates and has been scaled to multi-kilogram production. The functional group tolerance of Grubbs catalysts enables RCM on densely functionalized intermediates late in a synthetic sequence.
Fine chemicals and fragrances. Cross metathesis is used to prepare specialty alkenes and dienes for fragrance chemistry, including the synthesis of insect pheromones for agricultural pest control. The high Z selectivity of modern catalysts is critical because insect pheromone activity is often stereospecific.

Connections Master

Organometallic synthesis overview 15.09.01. This unit extends the treatment of metal-catalyzed reactions introduced in the parent unit. The metal carbene (alkylidene) is a distinct reactive intermediate not encountered in palladium cross-coupling; the [2+2] cycloaddition/cycloreversion mechanism is fundamentally different from the oxidative addition/transmetalation/reductive elimination cycle of Pd catalysis.
Palladium-catalyzed cross-coupling 15.09.02 pending. Both metathesis and cross-coupling form new C-C bonds catalytically, but the mechanisms and scope are complementary. Cross-coupling requires pre-functionalized partners (halides and organometallics) and forms C-C single bonds. Metathesis requires only alkenes and forms C=C double bonds. In retrosynthetic planning, the choice between a cross-coupling disconnection and a metathesis disconnection depends on the target's functional groups and the desired bond type.
Retrosynthetic analysis 15.10.01. RCM provides a powerful disconnection for cyclic targets: any ring containing a C=C double bond can be disconnected to a linear diene. This is a retrosynthetic transform that was unavailable before the development of practical metathesis catalysts, and it has become a standard disconnection in computer-assisted retrosynthesis programs.
Pericyclic reactions 15.08.01. The [2+2] cycloaddition step in the Chauvin mechanism is formally a pericyclic reaction, although it is facilitated by the metal center. The metallacyclobutane intermediate is analogous to the cyclobutane intermediate in thermal [2+2] cycloaddition, but the metal lowers the symmetry-imposed barrier, allowing the reaction to proceed under mild conditions.
Diels-Alder cycloaddition 15.05.03 pending. Enyne metathesis produces 1,3-dienes that can undergo Diels-Alder reactions, enabling tandem metathesis/cycloaddition sequences. The combination of ring-closing enyne metathesis followed by intramolecular Diels-Alder provides rapid access to polycyclic frameworks from simple linear precursors.

Historical notes Master

The history of olefin metathesis spans five decades of fundamental discovery and catalyst development.

In the 1950s and 1960s, industrial researchers at DuPont, Standard Oil, and Phillips Petroleum observed unusual alkene rearrangements over heterogeneous metal oxide catalysts. Employees at these companies reported that propene was converted to ethylene and butene in the presence of MoO3/Al2O3 and WO3/SiO2 catalysts. The reaction was initially called "olefin disproportionation" and was not understood mechanistically.

In 1971, Yves Chauvin and his student Jean-Louis Hérisson proposed the metal carbene mechanism that now bears Chauvin's name. The key insight was that the reaction proceeds through a metal alkylidene intermediate that undergoes [2+2] cycloaddition with an alkene, forming a metallacyclobutane that fragments to give a new alkene and a new metal alkylidene. This mechanism explained all the observed product distributions and predicted the existence of the metallacyclobutane intermediate, which was subsequently detected spectroscopically.

Richard Schrock at MIT began developing well-defined high-oxidation-state metal alkylidene catalysts in the 1980s. His molybdenum and tungsten alkylidene complexes were the first single-component metathesis catalysts, meaning they did not require a separate activator. The Schrock catalyst Mo(NAr)(CHCMe2Ph)(OCMe(CF3)2)2, reported in 1990, remains the most active metathesis catalyst known. However, its extreme sensitivity to air and moisture limited its adoption in synthetic organic chemistry.

Robert Grubbs at Caltech recognized that a more robust catalyst was needed for practical laboratory synthesis. In 1992, he reported the first-generation Grubbs catalyst RuCl2(PCy3)2(=CHPh). This ruthenium alkylidene complex was stable to air and moisture, tolerant of most functional groups, and commercially available. It made olefin metathesis accessible to synthetic chemists who were not specialists in organometallic chemistry. The second-generation Grubbs catalyst (1999), incorporating an NHC ligand, dramatically expanded the substrate scope to include sterically demanding and electronically deactivated alkenes.

The Hoveyda-Grubbs catalyst, developed by Amir Hoveyda in collaboration with Grubbs, introduced the chelating isopropoxybenzylidene design that improved catalyst stability and enabled recovery and recycling of the catalyst.

The 2005 Nobel Prize in Chemistry was awarded to Chauvin, Grubbs, and Schrock for the development of the olefin metathesis method. The Nobel citation recognized that metathesis had transformed organic synthesis by providing a catalytic, atom-economical, and broadly applicable method for forming carbon-carbon double bonds.

The development of Z-selective catalysts in the 2010s by Schrock (Mo biphenolate catalysts), Grubbs (Ru dithiolate catalysts), and Hoveyda (W oxo alkylidene catalysts) addressed the last major selectivity challenge in olefin metathesis. These catalysts enable the synthesis of Z alkenes with high stereocontrol, completing the toolkit for metathesis-based synthesis.

Current research frontiers include: catalysts for metathesis of challenging substrates (heteroatom-substituted alkenes, electron-poor alkenes), tandem metathesis/cross-coupling sequences, metathesis in aqueous and biological media, and the development of earth-abundant metal (Fe, Co) metathesis catalysts to replace the expensive Ru and Mo systems.

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  publisher = {Wiley-VCH},
  year = {2015},
  volumes = {1--3},
}