molecules Review Recent Advances in Asymmetric Iron Catalysis 1, 2, 3, Alessandra Casnati y , Matteo Lanzi y and Gianpiero Cera * 1 Laboratoire des Systèmes Complexes en Synthèse et Catalyse, Institut de Science et d’Ingénierie Supramoléculaires, Université de Strasbourg &CNRS, 8 Allèe Gaspard Monge, BP 70028, F-67083 Strasbourg, France; [email protected] 2 Laboratoire de Chemie Moléculaire (UMR CNRS 7509), Université de Strasbourg, ECPM 25 Rue Becquerel, 67087 Strasbourg, France; [email protected] 3 Dipartimento di Scienze Chimiche, della Vita e della Sostenibilità Ambientale, Università di Parma, Parco Area delle Scienze 17/A, I-43124 Parma, Italy * Correspondence: [email protected]; Tel.: +39-0521-905-294 These authors contributed equally to this work. y Academic Editor: Fabio Marchetti Received: 28 July 2020; Accepted: 25 August 2020; Published: 26 August 2020 Abstract: Asymmetric transition-metal catalysis represents a fascinating challenge in the field of organic chemistry research. Since seminal advances in the late 60s, which were finally recognized by the Nobel Prize to Noyori, Sharpless and Knowles in 2001, the scientific community explored several approaches to emulate nature in producing chiral organic molecules. In a scenario that has been for a long time dominated by the use of late-transition metals (TM) catalysts, the use of 3d-TMs and particularly iron has found, recently, a widespread application. Indeed, the low toxicity and the earth-abundancy of iron, along with its chemical versatility, allowed for the development of unprecedented and more sustainable catalytic transformations. While several competent reviews tried to provide a complete picture of the astounding advances achieved in this area, within this review we aimed to survey the latest achievements and new concepts brought in the field of enantioselective iron-catalyzed transformations. Keywords: iron; enantioselective; catalysis 1. Introduction Transition metal catalysis represents a powerful tool for the construction of highly functionalized molecules in organic synthesis. Among others, iron-catalyzed reactions [1–5] have recently become the most attractive alternative to the well-established palladium [6], rhodium [7], iridium [8] and ruthenium ones [9]. As a result of its low cost, compared to other d-metals, iron represents the most prominent metal for innovative and sustainable catalysis [10]. In addition, life evolution has integrated iron compounds in biological systems, thus resulting in low toxicity and therefore allowing high concentrations (>1300 ppm) of this metal in pharmaceuticals [11,12]. The chemistry of iron complexes is vast. Its position in the periodic table, just above ruthenium, justifies its wide applicability, mostly due to the various accessible oxidation states (from II to +VI). Low-valent iron − complexes proved to be active for catalytic nucleophilic substitutions, hydrogenation/hydrosilylation and cycloisomerization reactions [13,14]. Parallelly, the more common +II and +III iron species exhibit Lewis acidity that has been exploited in the electrophilic aromatic substitutions, such as Friedel–Crafts reactions [15]. Radical reactions and two electron couplings are also feasible under iron catalysis. The latter, in particular, involves a Fe(I)/Fe(III) manifold that parallels [16], in terms of reactivity, those operating in palladium-catalyzed cross-couplings [17]. The stereochemical control of chiral centers during chemical reactions is fundamental to access enantiopure compounds and thus avoiding tedious purifications. As a matter of fact, asymmetric Molecules 2020, 25, 3889; doi:10.3390/molecules25173889 www.mdpi.com/journal/molecules Molecules 2020, 25, 3889 2 of 29 Molecules 2020, 25, x FOR PEER REVIEW 2 of 30 catalysis withThe stereochemical transition metals control proved of chiral to be centers one of duri theng most chemical economical, reactions environmentally is fundamental to friendly access and efficientenantiopure approaches compounds for the synthesisand thus av ofoiding enantiomerically tedious purifications. pure molecules As a matter [18]. of fact, asymmetric Iron-catalyzedcatalysis with transition enantioselective metals proved reactions to be historically one of the most were economical, inspired by environmentally biological processes. friendlyIron is presentand in efficient several approaches enzymes, for such the as synthesis for instance, of enantiomerically the heme containing pure molecules cytochrome [18]. P450, known for its capabilityIron-catalyzed to promote C-H enantioselective oxygenations reactions [19] and historical carbenely were transfer inspired reactions by biological [20]. The processes. chemist’s Iron need to emulateis present nature in several led to enzymes, the development such as for ofinstance, a remarkable the heme number containing of iron-catalyzedcytochrome P450, enantioselective known for methodologies,its capability initiallyto promote using C‒H chiraloxygenations iron porphyrin [19] and carbene complexes transfer [21 reactions–23]. Major[20]. The advances chemist’s were need to emulate nature led to the development of a remarkable number of iron-catalyzed subsequently achieved with the introduction of chiral ligands such as oxazolines (i), NHCs (ii) or enantioselective methodologies, initially using chiral iron porphyrin complexes [21–23]. Major phosphine-basedadvances were ligands subsequently (iii) that achieved for a long with time the introd representeduction of the chiral most ligands commonly such as employed oxazolines approach (i), for highlyNHCs enantioselective (ii) or phosphine-based transformations. ligands (iii) More that recently,for a long new time strategies represented have the been most introduced commonly by the chemicalemployed community. approach For for example, highly enantioselective the use of achiral transformations. ligands, asymmetrically More recently, coordinatednew strategies around have the metalbeen center, introduced opened by access the chemical to catalytically community. active For exam chiral-at-metalple, the use of iron achiral complexes ligands, asymmetrically (iv). Additionally, asymmetriccoordinated induction around could the metal be also center, induced opened by a secondaccess to coordination catalytically sphereactive chiral-at-metal (v), usually constituted iron by biocomplexes macromolecules, (iv). Additionally, namely asymmetric enzymes or induction DNAs. could be also induced by a second coordination Thesphere aim (v), of usually this review constituted is to provide by bio an macromolecules, overview of the namely last advances enzymes in or enantioselective DNAs. iron-catalyzed reactions describingThe aim of theirthis review different is to working-modes provide an overview (i–v) toof inducethe last enantioselectivity.advances in enantioselective The last three iron- years catalyzed reactions describing their different working-modes (i–v) to induce enantioselectivity. The (2018, 2019 and 2020) will be covered with few references from the previous two years. last three years (2018, 2019 and 2020) will be covered with few references from the previous two years. 2. Chiral Oxazolines 2. Chiral Oxazolines ChiralChiral oxazolines oxazolines are a familyare a family of ligands of thatligands has beenthat extensivelyhas been extensively employed employed to develop to enantioselective develop transformations.enantioselective In transformations. the past three decades, In the past they thre receivede decades, remarkable they received attention remarkable due attention to their e duefficiency and versatilityto their efficiency [24–26 and]. Examples versatility including [24–26]. Examples early transition including metals, early transition such as metals, iron, are such however as iron,more recentare [27 however]. A chiral more spiro recent bisoxazoline [27]. A chiral ironspiro complex bisoxazoline was iron found complex catalytically was found active catalytically in promoting active the intramolecularin promoting enantioselective the intramolecular cyclopropanation enantioselective cy ofclopropanation indoles [28]. of This indole methodologys [28]. This methodology gives access to polycyclicgives compoundsaccess to polycyclic2 with two compounds contiguous 2 with all-carbon two contiguous quaternary all-ca stereogenicrbon quaternary centers. Chiralstereogenic ligand L1 was alsocenters. active Chiral in the ligand presence L1 was of also copper active precatalysts. in the presence Diff erentof copperα-aryl- precatalysts.α-diazoesters Different were α evaluated-aryl-α- in diazoesters were evaluated in the intramolecular cyclopropanation reaction providing high yields the intramolecular cyclopropanation reaction providing high yields and enantioselectivities (Scheme1). and enantioselectivities (Scheme 1). Scheme 1. Enantioselective intramolecular cyclopropanation of indoles. NaBARF = sodium tetrakis [3,5-bis(trifluoromethyl)phenyl]borate. Molecules 2020, 25, x FOR PEER REVIEW 3 of 30 MoleculesScheme2020, 251. ,Enantioselective 3889 intramolecular cyclopropanation of indoles. NaBARF = sodium tetrakis3 of 29 [3,5-bis(trifluoromethyl)phenyl]borate. TheThe cyclopropane-containing cyclopropane-containing final final product 2, due due to to its its donor-acceptor donor-acceptor feature, feature, allowed allowed multiple multiple additionaladditional transformations transformations to to access access complex complex polycy polycyclicclic scaffolds. scaffolds. The The same same class class of of chiral ligands α was selected selected