Iron-Catalyzed Olefin Metathesis: Recent Theoretical and Experimental Advances PDF

Review Chemistry—A European Journal doi.org/10.1002/chem.202201414 www.chemeurj.org Iron-Catalyzed Olefin Metathesis: Recent Theoretical and Experimenta...

Review Chemistry—A European Journal doi.org/10.1002/chem.202201414 www.chemeurj.org Iron-Catalyzed Olefin Metathesis: Recent Theoretical and Experimental Advances Benedikt W. Grau,[a] Alexander Neuhauser,[a] Sadig Aghazada,[b, c] Karsten Meyer,*[b] and Svetlana B. Tsogoeva*[a] Dedicated to the memory of Professor Robert H. Grubbs Chem. Eur. J. 2022, 28, e202201414 (1 of 17) © 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH  15213765, 2022, 62, Downloaded from https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.202201414 by National Sun-Yat-Sen, Wiley Online Library on [03/12/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Review Chemistry—A European Journal doi.org/10.1002/chem.202201414 Abstract: The “metathesis reaction” is a straightforward and or Ru(IV) have been developed and improved through ligand often metal-catalyzed chemical reaction that transforms two modifications. In addition, significant effort was invested to hydrocarbon molecules to two new hydrocarbons by ex- realize olefin metathesis with a non-toxic, bio-compatible and change of molecular fragments. Alkane, alkene and alkyne one of the most abundant elements in the earth’s crust; metathesis have become an important tool in synthetic namely, iron. First evidences suggest that low-valent Fe(II) chemistry and have provided access to complex organic complexes are active in olefin metathesis. Although the latter structures. Since the discovery of industrial olefin metathesis has not been unambiguously established, this review summa- in the 1960s, many modifications have been reported; thus, rizes the key advances in the field and aims to guide through increasing scope and improving reaction selectivity. Olefin the challenges. metathesis catalysts based on high-valent group six elements Introduction theories for olefin metathesis reaction were proposed: a pairwise mechanism (Scheme 1A) suggested by Calderon and Convenient construction of carbon carbon bonds is of utmost a non-pairwise mechanism (Scheme 1B) proposed by Chauvin importance in synthetic chemistry. The olefin metathesis in 1971. The proof for the prevalence of the non-pairwise reaction is one of the most prominent and elegant tools to mechanism was accomplished by cross-metathesis experiments build double bonds. Its applicability is almost unlimited and by Chauvin in 1971 and later by Katz (with cyclooctane, 2- even challenging syntheses can be handled with tailor-made butane and 4-octane) and by Grubbs in 1975 (depicted in catalysts. Olefin metathesis is used not only in the synthesis of Scheme 1). Deuterated and non-deuterated 1,7-octadiene simple polymers, such as polynorbornene, but also in syntheti- were brought to reaction with the heterogeneous catalyst cally challenging structures and pharmaceuticals, for exam- obtained from mixing of WCl6 and n-butyl lithium and the non- ple, Simeprevir. In 2005, Chauvin, Grubbs and Schrock were heterogeneous catalyst PhWCl3-AlCl3. As the resulting cyclo- awarded with the Nobel prize in chemistry for their pioneering hexene was inactive towards metathesis, the obtained mixture work on olefin metathesis. In addition to the olefin olefin of ethenes could be analyzed by gel permeation chromatog- metathesis reaction, recently reported carbonyl alkyne and raphy. Their ratios were found to be consistent with a non- carbonyl olefin[7b,8] metathesis reactions further expand the pairwise mechanism; regardless of catalysts. It is important to space of synthetically available structures. However, the latter mention that the individual reaction-steps are reversible, there- do not follow the Chauvin mechanism and the use of different fore, leading to the statistical yields of the desired olefins.[6c] types of catalysts is required, for example, Lewis acids. In 1989, Schrock reported the structurally authenticated Olefin disproportionation was achieved with ill-defined metallacyclobutane intermediate, a milestone in olefin meta- heterogeneous tungsten or molybdenum catalysts. Two main thesis catalysis, further supporting the non-pairwise mechanism (Scheme 2).[6c,14] Aiming at improving selectivity and achieving homogenous [a] Dr. B. W. Grau, A. Neuhauser, Prof. Dr. S. B. Tsogoeva catalysis, Schrock reported the molybdenum-based metalla- Organic Chemistry Chair I and Interdisciplinary Center for Molecular carbenes 1 (Figure 1), proficient to perform metathesis as a Materials (ICMM) Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) Nikolaus-Fiebiger-Straße, 10, 91058, Erlangen (Germany) E-mail: [email protected] Homepage: www.chemistry.nat.fau.eu/tsogoeva-group [b] Dr. S. Aghazada, Prof. Dr. K. Meyer Inorganic Chemistry Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) Egerlandstrasse 1, 91058 Erlangen (Germany) E-mail: [email protected] Homepage: www.inorgchem2.nat.fau.de [c] Dr. S. Aghazada Department of Chemistry and Applied Biosciences ETH Zurich Vladimir-Prelog-Weg 1–5, 8093 Zürich (Switzerland) Part of a Special Collection for the 8thEuChemSChemistry Congress 2022 consisting of contributions from selected speakers and conveners. To view the complete collection, visit 8th EuChemS Chemistry Congress © 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial License, which permits use, dis- tribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. Scheme 1. Proposed alternative mechanisms for olefin metathesis reaction. Chem. Eur. J. 2022, 28, e202201414 (2 of 17) © 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH  15213765, 2022, 62, Downloaded from https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.202201414 by National Sun-Yat-Sen, Wiley Online Library on [03/12/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Review Chemistry—A European Journal doi.org/10.1002/chem.202201414 novel, well-defined catalyst. These highly active molybdenum Schrock-type catalysts, such as 1, show the highest activity catalysts are also highly air-sensitive. Consequently, Grubbs’ towards olefin metathesis; thus, enabling metathesis with tri- or more stable Ru-based catalyst (2), developed in 1992, was even tetra-substituted alkenes.[6b,18] Regardless, in addition to preferred in the organic chemistry community. low selectivity, these catalysts suffer from incompatibility with Grubbs’ catalyst found a widespread application in syn- acids, alcohols and aldehydes. The advantages of bench-stable thesis, but the difficulty of catalyst recovery made further and functional group tolerant catalysts 2–5 comes with the lack improvements necessary. Subsequently, in 1999, Hoveyda of activity towards tri- or tetra-substituted olefines. The reported a conveniently recyclable variation of Grubbs’ catalyst dissociation of one of the phosphine ligands leads to the highly 4 (Figure 1). reactive on-cycle 14-electron species. Consequently, second generation catalysts sporting an N-heterocyclic carbene ligand Benedikt W. Grau was born in Hamburg Karsten Meyer studied chemistry at the (Germany) in 1991 He received his M.Sc. Ruhr-University of Bochum (Germany) degree in Chemistry from the Friedrich- and carried out his PhD thesis work Alexander-Universität Erlangen-Nürn- under the direction of Professor Karl berg (FAU) in 2017. The same year he Wieghardt at the Max-Planck-Institute began his graduate studies under the in Mülheim/Ruhr, receiving his Ph.D. supervision of Prof. S. B. Tsogoeva. His (Dr. rer. nat, summa cum laude) in area of research interest includes orga- January 1998. With a DFG fellowship, nocatalytic domino processes and Fe- Karsten proceeded to gain further re- catalyzed olefin metathesis. search experience in the laboratory of Professor Christopher Cummins at the Massachusetts Institute of Technology (Cambridge, USA). In 2001, he was Alexander Neuhauser was born in appointed to the faculty of the Univer- Traunstein (Germany) in 1994. After sity of California, San Diego (UCSD) and graduation from the Friedrich- was named an Alfred P. Sloan Fellow in Alexander-Universität Erlangen-Nürn- 2004. In 2006, he accepted an offer (C4/ berg (FAU) in 2019 with his MSc, he W3) to be the Chair of Inorganic & started his research in the group of General Chemistry at the Friedrich- Prof. S. B. Tsogoeva focusing on Fe- Alexander-Universität Erlangen-Nürn- catalyzed olefin metathesis and multi- berg (FAU), Germany. His research step domino reactions. focuses on the synthesis of task-specific ligand architectures, their transition and actinide metal complexes for the conversion of small molecules of bio- logical and industrial relevance as well Sadig Aghazada was born in Astara as the development of (electro- (Azerbaijan) in 1990. After graduation )catalysts in pre-organized materials, from Lomonosov Moscow State Univer- such as ionic liquids and ionic liquid sity (Russia) in 2013 with specialist crystals. degree, he earned his Ph.D. from EPFL (Switzerland). From 2018 to 2021, he Svetlana B. Tsogoeva graduated with was working as a postdoctoral fellow in Distinction in 1995 from St. Petersburg the Meyer lab at the Friedrich- State University, where she completed Alexander-Universität Erlangen-Nürn- her doctoral thesis in 1998. Then, she berg (FAU), focusing on transition metal moved to the Johann Wolfgang Goethe carbene complexes. In 2021, he joined University, Frankfurt am Main, Ger- ETH Zurich as an SNSF postdoctoral many, for postdoctoral research. In July fellow. 2000 she joined the Degussa AG Fine Chemicals Division as a research scien- tist. In January 2002 she was appointed a first junior professor in Germany at the Georg-August-University of Göttin- gen. Since February 2007, she has been professor of organic chemistry at the Friedrich-Alexander-Universität Erlan- gen-Nürnberg (FAU), Germany. Her re- search is currently focused on medicinal chemistry, multi-step domino processes, organocatalysis, autocatalytic transami- nation metathesis and Fe-catalyzed olefin metathesis. Chem. Eur. J. 2022, 28, e202201414 (3 of 17) © 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH  15213765, 2022, 62, Downloaded from https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.202201414 by National Sun-Yat-Sen, Wiley Online Library on [03/12/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Review Chemistry—A European Journal doi.org/10.1002/chem.202201414 (NHC) (3) were developed. The NHC ligand diminishes the re- Theoretical Attempts on Iron-Catalysed Olefin association of the trans-coordinating ligand resulting in im- Metathesis proved turnover numbers and catalytic activities even though it shows overall slower rates of activation compared to 2. Further improvements brought the introduction of an oxygen- As stated before, iron-catalyzed olefin metathesis has not been chelate, which stabilizes the catalyst and prevents decomposi- unambiguously realized yet. For the first-row transition metals, tion after reaction and during purification steps (see 4 and 5 in olefin cyclopropanation is preferred over metathesis. Also, due Figure 1). to lower bond-dissociation energies, in comparison to second As mentioned above, metathesis has many different and third-row transition metals, the first-row transition metal applications, for example in polymerization processes, such as alkylidene complexes tend to transfer the alkylidene moiety. ring opening metathesis polymerization (A, ROMP) or acyclic Regardless, the topic of iron-catalyzed metathesis was ad- diene metathesis (B, ADMET) (Scheme 3). Additionally, meta- dressed in multiple computational studies. thesis reactions are capable of yielding complex molecules by In 2014, Dixon and co-workers reported a study on bond ring closing metathesis (C, RCM), cross metathesis (D, CM) and dissociation energies (BDEs) of different metal carbene com- ring opening metathesis (E, ROM).[4a] The cross Yne-Ene meta- plexes (M = Fe, Ru, Os; Carbene: CH2, CHF, CF2). This was done thesis (F, YNE-ENE), the reaction between an alkyne and an following their findings in olefin metathesis with Schrock-type alkene, can also be considered as a special case of cross catalysts (M = Cr, Mo, W), where CHF or CF2 carbenes destabi- metathesis. lized the triplet state of the carbene, leading to a complex unfit Even though the current olefin metathesis catalysts provide for catalyzing metathesis reactions. Their model system was high yields under mild conditions and short reaction times, based on the Grubbs II catalyst and five key intermediate development of a sustainable, cost efficient, non-toxic, abun- structures were analyzed using high level CCSD(T) method with dant metal-based catalyst is highly desirable. One field of additional corrections to obtain near level accuracy (Scheme 4): significant current interest relates to the substitution of Whereas Ru and Os complexes unambiguously possess a ruthenium with its corresponding first-row transition metal singlet ground state, with large singlet-triplet and singlet- congener. A possible candidate, bearing the features listed quintet gaps, the Fe complex features an open-shell ground above, could be an iron-based catalyst, as metathesis is basically state with a singlet state high in energy. Therefore, the ground an olefin cycloaddition followed by a cycloreversion, and a states for iron complexes are mainly triplets or quintets, leading multitude of iron-catalyzed cycloadditions have already been to cyclopropanation rather than the desired cycloreversion for reported. While Lewis acid-catalyzed carbonyl-alkyne and this model structure. carbonyl-olefin metathesis using iron compounds as catalyst The dissociation of one of the ancillary ligands is believed to already have been established, iron-catalyzed olefin-metathesis lead to the 14-valence electron active species and, thus, M PH3 has not been realized so far and to the best of our knowledge BDEs were computed to increase activity in the order M = Fe < only one review exists, where selected publications on iron catalysed metathesis are mentioned amongst other first row transition metals. Therefore, an iron-derived carbene catalyst capable of performing olefin-olefin metathesis is highly desir- able. As this field of research is still in its infancy, this review sums up the recent key developments and findings concerning iron-catalyzed metathesis. Herein, we summarize the reported attempts toward the iron-based olefin metathesis catalysis. Scheme 2. Simplified reaction cycle of the Chauvin mechanism. Figure 1. Overview of different catalysts employed in olefin metathesis. Chem. Eur. J. 2022, 28, e202201414 (4 of 17) © 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH  15213765, 2022, 62, Downloaded from https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.202201414 by National Sun-Yat-Sen, Wiley Online Library on [03/12/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Review Chemistry—A European Journal doi.org/10.1002/chem.202201414 37.6 kcal and BDECF2 = 17.2 kcal/mol). It is important to mention that the low BDEs for the bonding of C2H4 to iron indicate that ethylene would be only weakly coordinated to the metal center. Figure 2 illustrates the reaction profile for the olefin cyclo- addition to the aforementioned complexes: All of the calculated Ru and Os complexes exhibit singlet ground states. For the iron complexes, the identification of the exact ground spin state was challenging due to the small energy differences between singlet, triplet and quintet states. For the calculations concerning different substituted meth- ylidene derivatives, the cycloaddition step was shown to be highly endothermic, which is another indication for the low performance of the iron-based catalyst. However, this could also mean that – instead of electron withdrawing groups – electron releasing groups on the alkylidene moiety are needed to render the cycloaddition less endothermic. In contrast to the reaction profile calculated for the Ru and Os model complexes, which not only form an energetically Scheme 3. Summary of olefin metathesis variations. more stable olefin complex, but also show only a slight increase in energy when going from structure III to IV (Figure 2, top), the metallacyclobutane formation is a highly endothermic process Ru < Os. For the iron methylene complex [FeCl2(CH2)(NHC)(PH3)], for the Fe model complex. Additionally problematic, the step PH3 has the lowest BDE of 10.7 kcal/mol, followed by the NHC from the π- to cis-complex (Figure 2, bottom III to IV) becomes (42.9 kcal/mol) and the methylidene (44.5 kcal/mol). Substitu- endothermic; hence, rendering the iron system un-fit for olefin tion of the methylidene’s one hydrogen with fluorine (= CHF) metathesis. increases the BDEs of PH3 (11.6 kcal/mol) and the NHC Also in 2014, Poater and co-workers reported static DFT (43.9 kcal/mol) slightly, but decreases the BDE for the alkylidene calculations for Grubbs-type iron complexes.[22a] For this study, to 38.5 kcal/mol. Difluoromethylene CF2 leads to an overall less simplified model structures, analogous to those addressed decrease in BDEs but the order remains the same as with by Dixon and co-workers, were calculated (Scheme 5), including monofluoromethylene CHF (BDEPH3 = 6.2 kcal/mol; BDENHC = their corresponding transition states. Scheme 4. Calculated reaction steps and intermediates by Dixon. Scheme 5. Metathesis reaction steps as calculated by Poater and co-workers.[22a] Chem. Eur. J. 2022, 28, e202201414 (5 of 17) © 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH  15213765, 2022, 62, Downloaded from https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.202201414 by National Sun-Yat-Sen, Wiley Online Library on [03/12/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Review Chemistry—A European Journal doi.org/10.1002/chem.202201414 Figure 2. Energy profile of formation of Grubbs-type complexes with different metal centers, calculated at the CCSD(T)/aD level of theory with ΔEZPE (BLYP/aD) (top), and different carbenes, calculated with CCSD(T)/aD level with energies at 0 K (bottom). The reaction profile illustrated in Figure 3 summarizes the tion mechanism with its intermediates is the same as the one obtained results. In the ground state, all calculated structures depicted in Figure 3. By calculating the geometries of the were found to have a singlet electronic state, except the two optimized structures I–VI and their respective transition states, 14-valence electron species II and IV which have a quintet another reaction energy profile was obtained, which is shown multiplicity. in Figure 4: The structure of species III (Scheme 5) was not stable, Poater and co-workers concluded that not only the collapsing directly to trans-metallacycle IV. Additionally, ring activation mechanism of the iron catalyst is similar to the Ru- opening did not lead to the expected π-coordinated complex based mechanism, starting with the initial dissociation of PPh3, V, but directly to VI. As the reaction profile does not contain but that these two systems perform through similar reaction stable intermediates, nor high energy barriers, the calculated profiles as well. profile could be consistent with an active catalyst, even though Solans-Monfort and co-workers studied the influence of it is slightly endothermic. various ligands on the metathesis reaction and the most In a subsequent work, the first part of the catalytic cycle common side reaction for transition metals, namely the cyclo- with methoxyethene was investigated. The calculated reac- Chem. Eur. J. 2022, 28, e202201414 (6 of 17) © 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH  15213765, 2022, 62, Downloaded from https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.202201414 by National Sun-Yat-Sen, Wiley Online Library on [03/12/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Review Chemistry—A European Journal doi.org/10.1002/chem.202201414 Figure 3. Reaction pathway computed by Poater and co-workers.[22a] Figure 4. Reaction pathway including transition states as calculated by Poater and co-workers. propanation reaction (Scheme 6), using DFT(OPBE)-D2 level energy profile for the reference Ru catalyst showed that of theory. cyclopropanation is endergonic and disfavored, if there is no Several model iron complexes, some with known ligands, spin-crossing to the triplet state (Figure 5). For the iron analogs, were compared to the reference system consisting of the significant structural differences between the singlet state second-generation Grubbs catalyst. Calculation of the reaction (trigonal bipyramidal (TBP) geometry) and the triplet state Chem. Eur. J. 2022, 28, e202201414 (7 of 17) © 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH  15213765, 2022, 62, Downloaded from https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.202201414 by National Sun-Yat-Sen, Wiley Online Library on [03/12/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Review Chemistry—A European Journal doi.org/10.1002/chem.202201414 and co-workers (see below), resulted in a sizable energetic preference of all investigated (S = 0) and closed-shell singlet with respect to high-spin (S = 1) triplet state complexes and for all reaction steps. Cyclopropanation also possesses high calculated energy barriers on the singlet potential energy surface and, consequently, [2 + 2] cycloreversion and therefore Scheme 6. Metathesis vs. the cyclopropanation side reaction for n = 3. metathesis, is kinetically preferred. In conclusion, low-valent and low-spin (especially closed-shell) Fe(II)-complexes could provide an alternative to the previously investigated Fe(IV) complexes, which are often charged complexes and are difficult (disordered square pyramidal (SP) geometry) of the metal- to prepare. The low barrier to cycloreversion has been linked by lacyclobutane intermediate were computed. Therefore, tetra- the authors to the (Craig-Möbius) aromaticity of the respective coordinated iron (IV) complexes with different ligands (Figure 6) closed-shell (orbital symmetry allowed) transition state were designed and their reaction energy profiles were studied structure. in silico. Rigid tridentate chelating ligands with strong σ- A more recent report from Solans-Monfort and co-workers donating groups were found to be the most promising in summarized the in silico study of selected penta- (rather than destabilizing the triplet state and favoring the singlet ground tetra-) coordinated iron complexes with regards to their state. proficiency in olefin metathesis (Figure 9). The two main benefits are, first, the stabilization of the First, model complexes with previously established ligands singlet state accompanied by a strengthening of the M=CH2 were examined for their ability to catalyze metathesis: bond, thus disfavoring the cyclopropanation reaction. Calcu- Ligands in complexes 11 and 12 were used to stabilize lations for 6 revealed a similar reaction energy profile as found high-valent oxo-complexes by Costas and co-workers. The for the Grubbs catalyst, which may provide access to iron- ligand of complex 13 is a simplified version of the TIMEN ligand catalyzed olefin metathesis if spin crossing to the triplet-state is system used to stabilize an Fe(IV) nitride complex by Meyer and avoided (Figure 5b). Secondly, the importance of σ-donors and co-workers. A Ni(II/III) complex of the ligand depicted in the geometry of ligands are stressed, which might be key to a complex 14 was used for C O bond formation in aryl successful design of Fe catalysts active in olefin metathesis. hydroxylation and methoxylations. Unfavorably, the meth- Inspired by reports of low-valent Fe-catalyzed [2 + 2] ylidene complexes illustrated in Figure 9 and their metal- cycloadditions,[23b] a 2017 theoretical study by Mauksch and lacyclobutane intermediates were computed to have high-spin Tsogoeva indicated that low oxidation state Fe(II), rather than ground states, thus favoring cyclopropanation over olefin Fe(IV) complexes, with the general structure L3Fe=CR2, may metathesis. Therefore, the authors decided to explore how the favor energetically the singlet over the triplet state in both reactivity of Fe(IV) complexes is influenced by ligand flexibility, carbene and metallacyclobutane complexes, therefore enabling by σ-donating abilities of the ligands and by the oxidation state facile olefin metathesis. To stabilize the implied singlet state of the iron center. Concerning the ligand flexibility, the authors of iron, ligands bearing both strong σ-donating as well as π- suggested, despite their own observation that modifications accepting abilities, for example, CO (as well as Fischer-type and influencing ligand flexibility are not favorable, that rigid N-heterocyclic carbenes), were employed, as in the trigonal- chelating ligands may stabilize the carbene singlet state and bipyramidal Fe(II) complex 10, depicted in Figure 7. In structures might therefore partly suppress alkene cyclopropanation. of this type, the closed-shell singlet (S = 0) ground state is Furthermore, the authors showed that high σ-donating abilities responsible for the suppression of the undesired cyclopropana- of the supporting chelates results in the stabilization of the tion side reaction. Please note, that the carbene is always singlet state, which is understood as a significant destabilization considered a dianionic ligand herein. of an iron d-orbital pointing towards the Cβ of the metallacycle, As the methylidene carbon must still be nucleophilic hinting at a potentially general strategy for achieving such a enough, as in Schrock-type carbenes, to allow metallacyclobu- singlet ground state. Additionally, neutral oxygen ligands trans tane formation (as this involves formation of a carbon-carbon to the carbene moiety, such as a furan, are proposed to disfavor bond), the resulting complexes assume an intermediate posi- alkene cyclopropanation, without destabilizing the singlet tion between the extremes of Fischer and Schrock carbenes. ground state. Based on this study, the most promising Electron exchange correlation generally favors triplet over candidates are depicted in Figure 10: singlet species, but this is true in particular for B3LYP, which Especially, 5-coordinate Fe(IV) complex 17 was mentioned contains the hybrid B3 exchange functional. Nevertheless, as the most promising candidate, possessing a reaction energy singlet and triplet state metallacyclobutane species are already profile reminiscent of that of a second generation Grubbs very close in energy at B3LYP (Figure 8) and a singlet with catalyst. Unfortunately, all of the selected complexes do appear pseudo-octahedral geometry was found being even lower in to prefer cyclopropanation over olefin metathesis kinetically. energy than the triplet. Moreover, calculations employing the For the square-pyramidal Fe(II) complexes, this was attributed BP86 density functional with a different (B88) exchange term, or to their „closed-shell“ 18 valence electron nature, which impairs with the OLYP functional, containing the OPTX exchange, olefin coordination, resulting in a high activation barrier for also applied by Solans-Montfort and co-workers and by Truhlar Chem. Eur. J. 2022, 28, e202201414 (8 of 17) © 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH  15213765, 2022, 62, Downloaded from https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.202201414 by National Sun-Yat-Sen, Wiley Online Library on [03/12/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Review Chemistry—A European Journal doi.org/10.1002/chem.202201414 Figure 5. Overview of charged and neutral iron (IV) complexes investigated by Solans-Monfort and co-workers. cycloreversion, while the Fe(IV) metallacyclobutane complexes center in low-valent iron complexes. To predict whether the do not possess singlet ground states. singlet or the triplet state is preferred, they defined a δ-value, Following the works by Solans-Monfort and co-workers as expressing the difference in the free energies of activation for well as that by Mauksch and Tsogoeva, Yang and Truhlar further the cyclopropanation minus the cycloreversion. The results addressed different types of chelating pincer ligands, calculat- suggest that higher δ-values imply a higher probability for the ing the electron density and formal negative charge on the iron cycloreversion and lower, more negative δ-values indicate a Chem. Eur. J. 2022, 28, e202201414 (9 of 17) © 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH  15213765, 2022, 62, Downloaded from https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.202201414 by National Sun-Yat-Sen, Wiley Online Library on [03/12/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Review Chemistry—A European Journal doi.org/10.1002/chem.202201414 Figure 6. Reaction energy profiles computed by Solans-Monfort and co-workers: a) with reference Grubbs-type Ru(IV) catalyst; b) with tridentate σ-donating ligand Fe(IV) catalyst. higher probability for the cyclopropanation. A linear correlation between a higher probability for cyclopropanation and a more positive partial charge on the Fe-center of the metallacyclobu- tane complex was observed. The most promising ligands, according to these calculations, are Kirchner’s PNP- (18) or CNC- type ligands (19), as used in the groups of Danopoulos and Crabtree. PDI (bis(imido)pyridine)-type ligands (20), however, exhibited a negative δ-value, making the cyclopropanation Figure 7. Structure of a TBP Fe(II) low spin closed-shell model metathesis more likely to occur (Figure 11). catalyst as proposed by Mauksch and Tsogoeva. A full catalytic cycle with all relevant intermediates and transition states was calculated with the (unrestricted) OPBE Figure 8. Reaction energy profile for metathesis vs. cyclopropanation pathways for TBP model complex 10, computed on singlet and triplet potential energy surface by Mauksch and Tsogoeva. At OLYP/6-31G* level, metallacyclopropane triplet is 8.7 kcal/mol (12.1 kcal/mol at BP86) higher in energy than closed- shell singlet. Figure 9. Examples of iron (IV) (n = 2) and iron (II) (n = 0) complexes studied by Solans-Monfort and co-workers. Chem. Eur. J. 2022, 28, e202201414 (10 of 17) © 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH  15213765, 2022, 62, Downloaded from https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.202201414 by National Sun-Yat-Sen, Wiley Online Library on [03/12/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Review Chemistry—A European Journal doi.org/10.1002/chem.202201414 Synthetic Attempts on Iron-Catalyzed Olefin Metathesis In 1966, Pettit and Jolly reported that upon protonolysis of [(η5- C5H5)Fe(CO)2(CH2OMe)], the iron methylidene [(η5-C5H5)Fe- (CO)2(CH2)] + (21) intermediate effects the cyclopropanation of olefines. Later, low temperature synthesis and low-temper- Figure 10. Furan-derived Fe(IV) complexes as proposed by Solans-Monfort ature NMR studies by Brookhart further suggested the and co-workers. formation of complexes 22 and 23 thus, supporting Pettit’s initial proposition. Brookhart also showed that the parent methylene can be stabilized at cryogenic conditions using a more electron-releasing ligand – 1,2-bis(diphenylphosphino)- ethane (dppe) instead of carbonyls, while Lapinte reported a room temperature stable iron methylene complex sporting the methylated Cp* (Cp* = pentamethylcylopentadienyl) and dppe ancillary ligands.[46,47] Only recently, Meyer and co-workers presented an unambiguous proof of the formation of a Figure 11. Examples of ligands studied computationally by Yang and Truhlar diamagnetic iron methylene complex, namely to be employed in their low-spin Fe(II) complexes. [(Cp*)(dppe)Fe=CH2] (24, see Figure 14). The thorough XRD structural analysis, together with a 57Fe Mössbauer and computational study, suggest an iron methylene complex exhibiting a Fischer-type electronic structure; yet, with consid- functional, containing OPTX exchange, which was shown to erable alkylidene character. Both σ- and π-bonds between the give promising results for high-spin iron complexes and for iron center and the methylene ligand are highly covalent. This the CNC-type ligand 19, indeed showing that the singlet state is results in substantial oxidation of the iron center and, therefore, lower in energy for all relevant steps for the tetra-coordinated a low 57Fe Mössbauer isomer shift value. Yet, no olefin meta- Fe(II) catalyst and that the transition state for the cyclo- thesis was reported with any of Pettit-type iron alkylidene propanation has a higher Gibbs free energy than that for the complexes. desired cycloreversion (Figure 12). Even though computations In 1997, Floriani et al. reported the synthesis of the Fe(II)- were carried out without spin-restriction, spin contamination diphenylmethylene complex 25, stabilized by a calixarene was found to be below 5 % for all investigated singlet species, ligand. This complex exhibits a high spin state, a high thermal which are therefore effectively closed-shell systems. stability and is resistant toward hydrolysis. Regardless, strong The authors even propose a route to the iron alkylidene iron-carbene bonding, cleavage of which can only be achieved complex starting from the [Fe(CNC)(N2)2] precursor, which can by acids or O2, makes 25 not suitable for olefin metathesis react with an alkyne to the respective alkylidene target via (Scheme 7). tautomerization. Unfortunately, the formation of this alkylidene Grubbs, following the discovery of the first generation of complex from an alkyne is not supported experimentally and, Ru-based catalysts for metathesis, reported the attempts to so far, there are no reports showing the successful synthesis of synthesize the Fe-based analogue by reacting FeCl2(PMe2Ph)2 the Fe(CNC)(=CHR) complex (Figure 13). with ethyl diazoacetate or diphenyldiazomethane. These reactions do not lead to the desired iron carbene complexes but, instead, the diazoalkanes insert into the Fe P bond without the release of N2; thus, forming the respective phosphazine complex (26, 27, 28, see Figure 15). Scheme 7. Structure, synthesis and reactivity of Floriani’s iron carbene complex. Chem. Eur. J. 2022, 28, e202201414 (11 of 17) © 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH  15213765, 2022, 62, Downloaded from https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.202201414 by National Sun-Yat-Sen, Wiley Online Library on [03/12/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Review Chemistry—A European Journal doi.org/10.1002/chem.202201414 Figure 12. Reaction energy profile of a tetra-coordinated Fe(II) complex with CNC ligand as calculated by Yang and Truhlar. More recently, Chirik and co-workers reported the syn- tion and heating these reactions mixtures to 85 °C resulted in its thesis of the iron diphenylmethylene complex [(RPDI)Fe(CPh2)] decomposition (Scheme 8). (32) starting from the dimer [{(RPDI)Fe(N2)}2(μ2-N2)] (31) and In 2015, Wolczanski, Meyer and co-workers introduced a diphenyldiazomethane. Complex 32 was described to have a series of formally Fe(IV) complexes (33, 34 and 35, Fig- high-spin Fe(II) center antiferromagnetically coupled to two ure 16). radicals on the bis(imino)pyridine and carbene ligands, which The low Mössbauer isomer shift value obtained for complex results in an S = 1 ground state. Probing the reactivity of 34 initially suggests a high oxidation state iron center. However, complex 32 towards various olefins at room temperature did the authors advocate that the low isomer shift could also not result in any reaction, neither metathesis nor cyclopropana- originate from the short and notably covalent Fe carbene Chem. Eur. J. 2022, 28, e202201414 (12 of 17) © 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH  15213765, 2022, 62, Downloaded from https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.202201414 by National Sun-Yat-Sen, Wiley Online Library on [03/12/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Review Chemistry—A European Journal doi.org/10.1002/chem.202201414 Figure 13. Overview of the most promising calculated and synthesized iron complexes as olefin metathesis catalysts over the years (HS = high spin, LS = low spin). Figure 14. Proposed complex 21 of Pettit and Jolly, Brookhart’s complexes 22 and 23 and Lapinte’s complex 24. Figure 15. Phosphazine complexes 26, 27 and 28 reported by Grubbs. bond. The positive charge of the complex could cause the Unfortunately, charge neutral complexes (Figure 17) are also contraction of d orbitals, which, in turn, may inhibit metathesis inactive in olefin metathesis. Arguably, strong Fe PMe3 bonding reactivity. Subsequently, Wolczanski and co-workers introduced in complexes 37, 38 and 39 prevents ligand dissociation and a series of uncharged “Fe(IV)” alkylidenes by treating 34 formation of the active species. Even complex 36, bearing a (depicted in Figure 16) with different nucleophiles and convert- dinitrogen molecule as a possibly labile ligand, was reportedly ing the coordinated imine to the amide.[52d,e] inactive. While complexes 36–39 have, computationally, Fe(II) character and, hence, the corresponding orbital for olefin Chem. Eur. J. 2022, 28, e202201414 (13 of 17) © 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH  15213765, 2022, 62, Downloaded from https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.202201414 by National Sun-Yat-Sen, Wiley Online Library on [03/12/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Review Chemistry—A European Journal doi.org/10.1002/chem.202201414 Scheme 8. Unsuccessful (top) and successful (bottom) synthesis of Chirik’s Fe(II) carbine. previously synthesized complexes by Wolczanski and co-work- ers have mainly Fe(II) character due to resonance stabilization (Figure 18, bottom). Yet again, the new Fe=CHR complex was inactive in olefin metathesis reaction. The resulting complex could be considered an Fe(II) vinyl complex with a cationic iron center and an anionic chelate with highly delocalized charge. Figure 16. Iron complexes synthesized by Wolczanski, Meyer and co- In conclusion, the synthesized compounds possess mainly a workers. d 6 electron configuration at the central iron ion and no activity towards olefin metathesis. The first successful iron-catalyzed polymerization of norbor- coordination and metallacyclobutane formation is principally nene, starting from a well-defined precatalyst complex, was available, the isopropyl group seems to thwart the catalytic achieved in 2021 by the group of Bukhryakov. With a high activity as it hinders the olefins’ approach. spin iron complex 40 (Scheme 9), featuring two bulky, mono- With these results in hand, a complex bearing a hydrogen dentate alkoxide ligands, norbornene ROMP with 16 % con- instead of an isopropyl group, yielding the corresponding version was achieved. Surprisingly, after addition of various Fe(II)=CHR species, was further investigated (Figure 18, top). alkylidene precursors known to catalyze ROMP with transition Calculations presented in this work also underline that metals, such as Ru, W or Au, the conversion of the monomer Figure 17. Neutral “Fe(IV)”-complexes synthesized by Wolczanski and co-workers.[52d,e] Chem. Eur. J. 2022, 28, e202201414 (14 of 17) © 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH  15213765, 2022, 62, Downloaded from https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.202201414 by National Sun-Yat-Sen, Wiley Online Library on [03/12/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Review Chemistry—A European Journal doi.org/10.1002/chem.202201414 Figure 18. Fe(II) resonance structures of formal Fe(“IV”) complexes investigated by Wolczanski and co-workers. diotacticity of the polymer stems from the active polynuclear iron clusters, which could form in the reaction mixture. Having studied late transition metal carbenes, the group of Iluc successfully synthesized the (distorted) trigonal-bipyramidal iron (II) carbene complex 41, capable of [2 + 2] cycloaddition of diphenylacetylene, resulting in a conjugated iron alkylidene 42 after rearrangement from the metallacyclobutene structure. Scheme 9. Polymerization of norbornene to syndiotactic polynorbornene by Upon treatment with another equivalent of diphenylacetylene, Bukhryakov and co-workers. extension of the ring system to an η 3-vinyl carbene with elimination of the N2 yields the stable 18-valence electron complex 43. Conceptually, this work emphasizes the possibility decreased. This led to the conclusion that no active iron of alkyne-olefin metathesis with a well-defined iron complex alkylidene species takes part in this reaction. The authors’ (Scheme 10). conclusion was further substantiated by the fact that the Very recently Takebayashi, Milstein and co-workers reported addition of other alkenes, such as cyclooctene or cycloocta-1,7- the successful ROMP of cyclic olefins (e. g., norbornene and its diene, to the operating reaction did not yield polymers with derivatives and of substituted cyclopropene) catalyzed by a those fragments incorporated. Regardless, addition of fluori- three-coordinate iron(II) catalyst 44 (Scheme 11). The catalyst nated alkoxides as an additive led to an improved conversion of features a bidentate pyridine-based ligand and (trimeth- up to 84 % after 24 h, resulting in highly stereoregular cis, ylsilyl)methylene, resulting in a trigonal planar high spin Fe(II) syndiotactic polynorbornene (Scheme 9). Presumably, the syn- complex. In contrast to all other catalysts, the formation of the carbene takes place after the coordination of norbornene by Scheme 10. Reaction of Iluc’s TBP iron (II) carbene complex with diphenylacetylene. Chem. Eur. J. 2022, 28, e202201414 (15 of 17) © 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH  15213765, 2022, 62, Downloaded from https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.202201414 by National Sun-Yat-Sen, Wiley Online Library on [03/12/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Review Chemistry—A European Journal doi.org/10.1002/chem.202201414 Scheme 11. Formation of Takebayashi/Milstein’s Fe(II) alkylidene and ROMP of norbornene. elimination of the alkyl ligands’ Hα and aromatization of suggested a triplet ground state of the involved pyridine (45–46), which is proposed to be the rate determining metallacyclobutane. Hence, to proceed towards broad scope step. To facilitate this step, 0.5 equivalents of water were added, iron-catalyzed olefin metathesis, further elucidation of mecha- which resulted in a higher activity of the catalyst. After this, the nistic details appears essential. reaction follows the Chauvin mechanism with formation of a Summarizing, and as the preparation of actual Fe(IV) metallacyclobutane intermediate (which the authors proposed carbenes, previously considered to be necessary in order to to be in a triplet state) and subsequent topomerisation of the fulfil the “d4-rule”,[52a] still remains challenging, recent theoretical complex (internal rotation of Fe=C bond from apical to and synthetic work suggests that Fe(II) carbenes may instead equatorial position), resulting in pure trans, isotactic polynor- offer a more promising route towards successful iron-based bornene product with high molecular weight. metathesis catalysis. By combining such low oxidation state iron centers with strong ligands and by combining the strengths of both in silico design and concurrent synthetic Conclusion work, realization of broadly applicable iron-catalyzed olefin metathesis could be within reach in the near future. Iron, one of the most abundant elements in the earth‘s crust, is in focus of extensive research in catalysis. In spite of numerous attempts over the decades to replace toxic, rare and expensive Acknowledgements Ru in homogenous catalysts for olefin metathesis by well- defined iron catalysts, it turned out a major obstacle to replace The authors thank the Graduate School Molecular Science Ru(IV) catalysts by Fe(IV) catalysts. Hence, focus in theoretical (GSMS) and the Interdisciplinary Center for Molecular Materials investigations and synthetic work turned, since recently, on (ICMM) for research support. S.A. acknowledges a fellowship low-valent Fe(II) catalysts.[32,40,53,55] To date, only two examples of from the Swiss National Science Foundation (P400P2_191101). iron-catalyzed metathesis with such (high-spin) Fe(II) catalysts Open Access funding enabled and organized by Projekt DEAL. have been demonstrated.[53,55] A major problem, identified as undesired competing alkene cyclopropanation, is linked to the often-preferred high spin ground state of iron-derived com- Conflict of Interest plexes. To overcome this issue, the role of the ligand environ- ment and the iron ion’s formal oxidation and spin state appears The authors declare no conflict of interest. crucial and warrants further mechanistic investigations. In particular, while in recent theoretical work therefore a closed shell involved Chauvin intermediate is proposed (as is also the case for Ru),[32,40] preliminary results of DFT calculations Chem. Eur. J. 2022, 28, e202201414 (16 of 17) © 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH  15213765, 2022, 62, Downloaded from https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.202201414 by National Sun-Yat-Sen, Wiley Online Library on [03/12/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Review Chemistry—A European Journal doi.org/10.1002/chem.202201414 Data Availability Statement R. Stragies, M. Schuster, S. Blechert, Angew. Chem. Int. Ed. 1997, 36, 2518–2520; Angew. Chem. 1997, 109, 2628–2630. a) A. Poater, S. V. Chaitanya Vummaleti, E. Pump, L. Cavallo, Dalton Data sharing is not applicable to this article as no new data Trans. 2014, 43, 11216–11220; b) A. Poater, Catal. Commun. 2014, 44, 2– were created or analyzed in this study. 5. a) C. Bolm, J. Legros, J. Le Paih, L. Zani, Chem. Rev. 2004, 104, 6217– 6254; b) J. M. Hoyt, V. A. Schmidt, A. M. Tondreau, P. J. Chirik, Science Keywords: iron catalysis · ligands · metathesis catalysts · olefin 2015, 349, 960–963. I. Bauer, H. J. Knolker, Chem. Rev. 2015, 115, 3170–3387. metathesis · olefins D. S. Belov, G. Tejeda, K. V. Bukhryakov, ChemPlusChem 2021, 86, 924– 937. É. de Brito Sá, L. Rodríguez-Santiago, M. Sodupe, X. Solans-Monfort, Organometallics 2016, 35, 3914–3923. a) U. M. Dzhemilev, R. I. Khusnutdinov, G. A. Tolstikov, J. Organomet. M. Vasiliu, A. J. Arduengo, D. A. Dixon, J. Phys. Chem. C 2014, 118, Chem. 1991, 409, 15–65; b) M. Schuster, S. Blechert, Angew. Chem. Int. 13563–13577. Ed. 1997, 36, 2037–2056; c) M. García-Melchor, X. Solans-Monfort, G. M. Vasiliu, S. G. Li, A. J. Arduengo, D. A. Dixon, J. Phys. Chem. C 2011, Ujaque, in Comprehensive Inorganic Chemistry II (Eds: J. Reedijk, K. 115, 12106–12120. Poeppelmeier), Elsevier Ltd 2013, pp. 767–805. J. H. Van Vleck, Phys. Rev. 1932, 41, 208–215. a) G. Liu, H. He, J. Wang, Adv. Synth. Catal. 2009, 351, 1610–1620; b) M. J. A. Poater, E. Pump, S. V. C. Vummaleti, L. Cavallo, Chem. Phys. Lett. 2014, Koh, R. K. Khan, S. Torker, M. Yu, M. S. Mikus, A. H. Hoveyda, Nature 610, 29–32. 2015, 517, 181–186; c) K. Jung, K. Kim, J.-C. Sung, T. S. Ahmed, S. H. H. Lebel, J. F. Marcoux, C. Molinaro, A. B. Charette, Chem. Rev. 2003, 103, Hong, R. H. Grubbs, T.-L. Choi, Macromolecules 2018, 51, 4564–4571. 977–1050. a) J. A. Wisner, P. D. Beer, M. G. Drew, M. R. Sambrook, J. Am. Chem. Soc. M. Mauksch, S. B. Tsogoeva, Chem. Eur. J. 2017, 23, 10264–10269. 2002, 124, 12469–12476; b) A. Dewaele, L. Meerten, L. Verbelen, S. Eyley, M. Radon, Phys. Chem. Chem. Phys. 2014, 16, 14479–14488. W. Thielemans, P. Van Puyvelde, M. Dusselier, B. Sels, ACS Sustainable M. Swart, J. Chem. Theory Comput. 2008, 4, 2057–2066. Chem. Eng. 2016, 4, 5943–5952. N. C. Handy, A. J. Cohen, J. Mol. Phys. 2009, 99, 403–412. a) S. G. Aitken, A. D. Abell, Aust. J. Chem. 2005, 58, 3–13; b) A. Gradillas, É. de Brito Sá, L. Rodríguez-Santiago, M. Sodupe, X. Solans-Monfort, J. Pérez-Castells, Angew. Chem. Int. Ed. 2006, 45, 6086–6101; Angew. Organometallics 2018, 37, 1229–1241. Chem. 2006, 118, 6232–6247; c) V. Farina, A. Horváth, in Handbook of G. Olivo, O. Cusso, M. Costas, Chem. Asian J. 2016, 11, 3148–3158. Metathesis (Eds.: R. H. Grubbs, A. G. Wenzel, D. J. O’Leary, E. Khosravi), C. Vogel, F. W. Heinemann, J. Sutter, C. Anthon, K. Meyer, Angew. Chem. John Wiley & Sons, Weinheim, 2015, pp. 633–658. Int. Ed. 2008, 47, 2681–2684; Angew. Chem. 2008, 120, 2721–2724. A. Horvath, D. Depre, A. V. WA, S. L. Wuyts, S. R. Harutyunyan, G. Binot, J. W. Zhou, J. W. Schultz, N. P. Rath, L. M. Mirica, J. Am. Chem. Soc. 2015, Cuypers, W. Couck, D. V. Den Heuvel, J. Org. Chem. 2019, 84, 4932–4939. 137, 7604–7607. a) R. H. Grubbs, Angew. Chem. Int. Ed. 2006, 45, 3760–3765; Angew. B. Yang, D. G. Truhlar, Organometallics 2018, 37, 3917–3927. Chem. 2006, 118, 3845–3850; b) R. R. Schrock, Angew. Chem. Int. Ed. A. A. Danopoulos, J. A. Wright, W. B. Motherwell, Chem. Commun. 2005, 2006, 45, 3748–3759; Angew. Chem. 2006, 118, 3832–3844; c) Y. 784–786. Chauvin, Angew. Chem. Int. Ed. 2006, 45, 3740–3747; Angew. Chem. E. Peris, J. Mata, J. A. Loch, R. H. Crabtree, Chem. Commun. 2001, 201– 2006, 118, 3824–3831; d) A. H. Hoveyda, A. R. Zhugralin, Nature 2007, 202. 450, 243–251. M. Swart, A. R. Groenhof, A. W. Ehlers, K. Lammertsma, J. Phys. Chem. A a) M. R. Becker, R. B. Watson, C. S. Schindler, Chem. Soc. Rev. 2018, 47, 2004, 108, 5479–5483. 7867–7881; b) B. W. Grau, S. B. Tsogoeva, Catalysts 2020, 10, 1092. P. W. Jolly, R. Pettit, J. Am. Chem. Soc. 1966, 88, 5044–5045. a) J. R. Ludwig, P. M. Zimmerman, J. B. Gianino, C. S. Schindler, Nature M. Brookhart, G. O. Nelson, J. Am. Chem. Soc. 1977, 99, 6099–6101. 2016, 533, 374–379; b) C. Saa, Angew. Chem. Int. Ed. 2016, 55, 10960– M. Brookhart, J. R. Tucker, T. C. Flood, J. Jensen, J. Am. Chem. Soc. 1980, 10961; Angew. Chem. 2016, 128, 11120–11121; c) J. R. Ludwig, S. Phan, 102, 1203–1205. C. C. McAtee, P. M. Zimmerman, J. J. Devery, 3rd, C. S. Schindler, J. Am. C. Roger, C. Lapinte, J. Chem. Soc. Chem. Commun. 1989, 1598–1600. Chem. Soc. 2017, 139, 10832–10842; d) C. C. McAtee, P. S. Riehl, C. S. S. Aghazada, D. Munz, F. W. Heinemann, A. Scheurer, K. Meyer, J. Am. Schindler, J. Am. Chem. Soc. 2017, 139, 2960–2963; e) C. Schindler, J. Chem. Soc. 2021, 143, 17219–17225. Ludwig, Synlett 2017, 28, 1501–1509; f) P. S. Riehl, D. J. Nasrallah, C. S. M. Giusti, E. Solari, L. Giannini, C. Floriani, A. Chiesi-Villa, C. Rizzoli, Schindler, Chem. Sci. 2019, 10, 10267–10274. Organometallics 1997, 16, 5610–5612. R. L. Banks, G. C. Bailey, Ind. Eng. Chem. Prod. Res. Dev. 1964, 3, 170–173. J. Louie, R. H. Grubbs, Organometallics 2001, 20, 481–484. N. Calderon, Acc. Chem. Res. 1972, 5, 127–132. S. K. Russell, J. M. Hoyt, S. C. Bart, C. Milsmann, S. C. E. Stieber, S. P. a) P. Jean-Louis Hérisson, Y. Chauvin, Makromol. Chem. 1971, 141, 161– Semproni, S. DeBeer, P. J. Chirik, Chem. Sci. 2014, 5, 1168–1174. 176; b) T. J. Katz, J. McGinnis, J. Am. Chem. Soc. 1975, 97, 1592–1594. a) O. Eisenstein, R. Hoffmann, A. R. Rossi, J. Am. Chem. Soc. 1981, 103, R. H. Grubbs, P. L. Burk, D. D. Carr, J. Am. Chem. Soc. 1975, 97, 3265– 5582–5584; b) T. J. Katz, Angew. Chem. Int. Ed. 2005, 44, 3010–3019; 3267. Angew. Chem. 2005, 117, 3070–3079; c) B. M. Lindley, A. a. Swidan, E. B. J. Feldman, J. S. Murdzek, W. M. Davis, R. R. Schrock, Organometallics Lobkovsky, P. T. Wolczanski, M. Adelhardt, J. Sutter, K. Meyer, Chem. Sci. 1989, 8, 2260–2265. 2015, 6, 4730–4736; d) B. M. Lindley, B. P. Jacobs, S. N. MacMillan, P. T. P. Jean-Louis Hérisson, Y. Chauvin, Makromol. Chem. 1971, 141, 161– Wolczanski, Chem. Commun. 2016, 52, 3891–3894; e) B. P. Jacobs, R. G. 176. Agarwal, P. T. Wolczanski, T. R. Cundari, S. N. MacMillan, Polyhedron R. R. Schrock, J. S. Murdzek, G. C. Bazan, J. Robbins, M. Dimare, M. 2016, 116, 47–56. Oregan, J. Am. Chem. Soc. 1990, 112, 3875–3886. D. S. Belov, L. Mathivathanan, M. J. Beazley, W. B. Martin, K. V. S. T. Nguyen, L. K. Johnson, R. H. Grubbs, J. W. Ziller, J. Am. Chem. Soc. Bukhryakov, Angew. Chem. Int. Ed. 2021, 60, 2934–2938; Angew. Chem. 1992, 114, 3974–3975. 2021, 133, 2970–2974. a) J. S. Kingsbury, J. P. A. Harrity, P. J. Bonitatebus, A. H. Hoveyda, J. Am. M. R. Hoffbauer, V. M. Iluc, J. Am. Chem. Soc. 2021, 143, 5592–5597. Chem. Soc. 1999, 121, 791–799; b) S. B. Garber, J. S. Kingsbury, B. L. Gray, S. Takebayashi, M. A. Iron, M. Feller, O. Rivada-Wheelaghan, G. Leitus, Y. A. H. Hoveyda, J. Am. Chem. Soc. 2000, 122, 8168–8179. Diskin-Posner, L. J. W. Shimon, L. Avram, R. Carmieli, S. G. Wolf, I. Cohen- a) G. C. Fu, R. H. Grubbs, J. Am. Chem. Soc. 1992, 114, 5426–5427; b) J. Ofri, R. A. Sanguramath, R. Shenhar, M. Eisen, D. Milstein, Nat. Catal. Santamaría, E. Aguilar, Org. Chem. Front. 2016, 3, 1561–1588. 2022, 5, 494–505. a) N. Mukherjee, S. Planer, K. Grela, Org. Chem. Front. 2018, 5, 494–516; b) W. Kosnik, D. Lichosyt, M. Sniezek, A. Janaszkiewicz, K. Wozniak, M. Malinska, B. Trzaskowski, A. Kajetanowicz, K. Grela, Angew. Chem. Int. Ed. 2022, 61, e202201472. Manuscript received: May 7, 2022 M. S. Sanford, M. Ulman, R. H. Grubbs, J. Am. Chem. Soc. 2001, 123, 749– Accepted manuscript online: June 30, 2022 750. Version of record online: September 8, 2022 Chem. Eur. J. 2022, 28, e202201414 (17 of 17) © 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH