catalysts Review Iron-Catalyzed Carbonyl–Alkyne and Carbonyl–Olefin Metathesis Reactions Benedikt W. Grau and Svetlana B. Tsogoeva * Organic Chemistry Chair I and Interdisciplinary Center for Molecular Materials (ICMM), Friedrich Alexander University Erlangen-Nürnberg, Nikolaus-Fiebiger-Straße 10, 91058 Erlangen, Germany; [email protected] * Correspondence: [email protected]; Tel.: +49-9131-85-65573; Fax: +49-9131-85-65501 Received: 20 August 2020; Accepted: 4 September 2020; Published: 21 September 2020 Abstract: Construction of carbon–carbon bonds is one of the most important tools for the synthesis of complex organic molecules. Among multiple possibilities are the carbonyl–alkyne and carbonyl–olefin metathesis reactions, which are used to form new carbon–carbon bonds between carbonyl derivatives and unsaturated organic compounds. As many different approaches have already been established and offer reliable access to C=C bond formation via carbonyl–alkyne and carbonyl–olefin metathesis, focus is now shifting towards cost efficiency, sustainability and environmentally friendly metal catalysts. Iron, which is earth-abundant and considered as an eco-friendly and inexpensive option in comparison to traditional metal catalysts, fulfils these requirements. Hence, the focus of this review is on recent advances in the iron-catalyzed carbonyl–alkyne, carbonyl–olefin and related C–O/C–O metathesis reactions. The still large research potential for ecologically and economically attractive and sustainable iron-based catalysts is demonstrated. Keywords: iron catalysts; carbonyl-olefin metathesis; carbonyl-alkyne metathesis; C=C bond formations 1. Introduction The formation of carbon–carbon bonds is one of the most important goals in chemistry [1]. For fast, efficient and selective coupling, catalysis via metal salts or metal complexes is an elegant option with versatile applications in academic research or industry [2–4]. Among known efficient C–C bond formation methods are metal-catalyzed cycloadditions, which provide attractive alternatives to photochemical [5], radical [6] or thermal [7,8] cyclization reactions, as they do not require expensive photosensitizers and mostly work under mild conditions. One of the most important methodologies is the metal-catalyzed olefin–olefin metathesis reaction (Scheme1a), which is a powerful tool for the formation of carbon–carbon double bonds with a wide range of applications [9–12]. It provides access to unsaturated compounds which are otherwise impossible to prepare, pharmaceutics in particular [13]. In addition to the olefin metathesis reaction, carbonyl–alkyne and carbonyl–olefin metathesis reactions offer an alternative possibility to generate carbon–carbon bonds. In contrast to olefin–olefin metathesis (as shown in Scheme1a), carbonyl–alkyne (Scheme1b) and carbonyl–olefin metathesis (Scheme1c) do not follow the Chauvin mechanism, even though the reaction proceeds via a formal [2 + 2] cycloaddition with an oxetene or oxetane as the intermediate [14,15]. As the reaction mechanism differs from olefin metathesis, use of a different type of catalyst is required. Most common metal catalysts for these reactions are Lewis acids, which activate both the carbonyl and the oxetene/oxetane species during the reaction [16,17]. A special case is the C–O/C–O metathesis reaction (as depicted in Scheme1d), which forms a new C–O bond resulting in cyclic ether derivatives. Even though the reaction does not form a new C–C bond, the reaction can be considered as a ring-closing C–O/C–O metathesis of aliphatic ethers [18]. Catalysts 2020, 10, 1092; doi:10.3390/catal10091092 www.mdpi.com/journal/catalysts Catalysts 2020, 10, x FOR PEER REVIEW 2 of 13 Catalysts 2020, 10, 1092 2 of 13 While many catalytic systems have already been reported, mainly employing organic Lewis acids [19] or metal-based Lewis acids [20], the development of new sustainable, cost-saving, earth-abundant metal-containing catalysts is highly desirable in today’s chemistry [21,22]. Recently, FeCl3, which fulfils the abovementioned requirements, has been established for carbonyl-olefin and carbonyl-alkyne metathesis as a reliable catalyst. Therefore, the current review summarizes all recent Catalystsdevelopments 2020, 10, x in FOR this PEER field REVIEW of research and related Fe-catalyzed C–O/C–O metathesis reaction. 2 of 13 Scheme 1. Selected metathesis reactions: (a) olefin–olefin metathesis, (b) carbonyl–alkyne metathesis, (c) carbonyl–olefin metathesis and (d) ring-closing C–O/C–O metathesis. A special case is the C–O/C–O metathesis reaction (as depicted in Scheme 1d), which forms a new C–O bond resulting in cyclic ether derivatives. Even though the reaction does not form a new C–C bond, the reaction can be considered as a ring-closing C–O/C–O metathesis of aliphatic ethers [18]. While many catalytic systems have already been reported, mainly employing organic Lewis acids [19] or metal-based Lewis acids [20], the development of new sustainable, cost-saving, earth- abundant metal-containing catalysts is highly desirable in today’s chemistry [21,22]. Recently, FeCl3, which fulfils the abovementioned requirements, has been established for carbonyl-olefin and carbonyl-alkyne metathesis as a reliable catalyst. Therefore, the current review summarizes all recent Scheme 1. Selected metathesis reactions: (a) olefin–olefin metathesis, (b) carbonyl–alkyne metathesis, developmentsScheme 1. Selectedin this field metathesis of research reactions: and ( are) olefin–olefinlated Fe-catalyzed metathesis, C–O/C–O (b) carbonyl–alkyne metathesis reaction.metathesis, ((cc)) carbonyl–olefin carbonyl–olefin metathesis and ( d) ring-closing C–OC–O/C–O/C–O metathesis. 2. Results Results A special case is the C–O/C–O metathesis reaction (as depicted in Scheme 1d), which forms a new2.1. Iron-Catalyzed Iron-CatalyzedC–O bond resulting C–O/C–O C–O/C–O in cyclic Ring-Closing ether derivatives. Metathesis Even though the reaction does not form a new C–C bond, the reaction can be considered as a ring-closing C–O/C–O metathesis of aliphatic ethers 3 3 [18]. As the first first example of a related related metathesis metathesis reaction we chose the C(sp )–O/C(sp)–O/C(sp )–O)–O ring-closing ring-closing reactionWhile reported many bycatalytic Morandi systems and co-workers have already [[18].18]. b Th Thiseenis reported,single single bond mainly “metathesis” “metathesis” employing reaction organic is a Lewis acidsacid-catalyzed [19] or metal-based ring closing, Lewis which acids transforms [20], the linear development diethers into of new five- five- sustainable, or six-membered cost-saving, cyclic earth-ethers (Scheme2 2).). abundant metal-containing catalysts is highly desirable in today’s chemistry [21,22]. Recently, FeCl3, which fulfils the abovementioned requirements, has been established for carbonyl-olefin and carbonyl-alkyne metathesis as a reliable catalyst. Therefore, the current review summarizes all recent developments in this field of research and related Fe-catalyzed C–O/C–O metathesis reaction. 2. Results Scheme 2. GeneralGeneral equation equation of the reaction developed by Morandi and co-workers. 2.1. Iron-CatalyzedDifferentDifferent substitution C–O/C–O patterns,Ring-Closing including Metathesis benzyl groups with electron donating and electron withdrawing groups as well as methyl groups an andd heteroatoms in the chain, are tolerated in the As the first example of a related metathesis reaction we chose the C(sp3)–O/C(sp3)–O ring-closing reaction system. To To investigate if the the generation generation of of dimethyl-ether dimethyl-ether is is the the driving driving force force of of the the reaction, reaction, reaction reported by Morandi and co-workers [18]. This single bond “metathesis” reaction is a Lewis experiments werewere performedperformed with with 1,5-pentanediol 1,5-pentanediol etherified etherified with with diff differenterent alcohols alcohols (MeOH, (MeOH, PrOH PrOH and acid-catalyzed ring closing, which transforms linear diethers into five- or six-membered cyclic ethers andButOH). ButOH). As the As yield the ofyield the cycloetherof the cycloether was identical, was iden it couldtical, beit could concluded be concluded that dimethyl-ether that dimethyl-ether formation (Scheme 2). formationis not the key is not driving the key force driving of the reaction.force of the Additional reaction. investigations Additional investigations showed also thatshowed generation also that of generationthe cyclic ether of the is irreversible.cyclic ether Inis conclusionirreversible. the In authors conclusion suggest the a authors bimolecular suggest mechanism, a bimolecular which wasmechanism, supported which by a crossoverwas supported experiment by a withcrossove methyl-r experiment and propyl-ether with methyl- derivatives. and Thepropyl-ether proposed derivatives.mechanismCatalysts 2020, 10 isThe, depictedx FOR proposed PEER in REVIEW Schememechan 3ism: is depicted in Scheme 3: 3 of 13 Scheme 2. General equation of the reaction developed by Morandi and co-workers. Different substitution patterns, including benzyl groups with electron donating and electron withdrawing groups as well as methyl groups and heteroatoms in the chain, are tolerated in the reaction system. To investigate if the generation of dimethyl-ether is the driving force of the reaction, experiments were performed with 1,5-pentanediol etherified with different alcohols (MeOH, PrOH Scheme 3. Proposed mechanism for the C–O/C–O metathesis reaction. and ButOH). As theScheme yield of3. Proposedthe cycloether