molecules Review Ruthenacycles and Iridacycles as Transfer Hydrogenation Catalysts Vincent Ritleng 1,* and Johannes G. de Vries 2,* 1 Ecole européenne de Chimie, Polymères et Matériaux, Université de Strasbourg, CNRS, LIMA, UMR 7042, 25 rue Becquerel, 67087 Strasbourg, France 2 Leibniz Institut für Katalyse, e. V. Albert-Einstein Strasse 29a, 18059 Rostock, Germany * Correspondence: [email protected] (V.R.); [email protected] (J.G.d.V.) Abstract: In this review, we describe the synthesis and use in hydrogen transfer reactions of ruthenacy- cles and iridacycles. The review limits itself to metallacycles where a ligand is bound in bidentate fashion to either ruthenium or iridium Via a carbon–metal sigma bond, as well as a dative bond from a heteroatom or an N-heterocyclic carbene. Pincer complexes fall outside the scope. Described are applications in (asymmetric) transfer hydrogenation of aldehydes, ketones, and imines, as well as reductive aminations. Oxidation reactions, i.e., classical Oppenauer oxidation, which is the reverse of transfer hydrogenation, as well as dehydrogenations and oxidations with oxygen, are described. Racemizations of alcohols and secondary amines are also catalyzed by ruthenacycles and iridacycles. Keywords: metallacycle; ruthenium; iridium; transfer hydrogenation; oxidation; ketone 1. Introduction In this review, the use of cyclometalated complexes based on ruthenium and iridium Citation: Ritleng, V.; de Vries, J.G. in hydrogen transfer reactions is described. In the definition we use here, a cyclometalated Ruthenacycles and Iridacycles as complex has one anionic carbon–metal σ-bond and is additionally stabilized by a single Transfer hydrogenation Catalysts. intramolecular dative bond from the same ligand [1]. Thus, metal pincer complexes are Molecules 2021, 26, 4076. https:// outside the scope of this review. doi.org/10.3390/molecules26134076 2. Ruthenacycles as Transfer Hydrogenation Catalysts Academic Editor: Michal Szostak The transfer hydrogenation (TH) of ketones is by far the most studied reaction with ruthenacycles, in particular with CN-ruthenacycles, as will become apparent in the fol- Received: 4 June 2021 lowing pages. Most of the published work deals with racemic reductions. Noteworthy, Accepted: 29 June 2021 Published: 3 July 2021 the most important contribution in asymmetric transfer hydrogenation comes from the work of Pfeffer and his collaborators. This review is dedicated to Michel Pfeffer for his pioneering work in this field. Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in 2.1. Transfer Hydrogenation of Ketones published maps and institutional affil- iations. The first examples of catalytic application of cyclometalated ruthenium complexes in ketone transfer hydrogenation appeared in 2004 in two successive contributions from the group of Baratta [2,3]. These reports followed a publication from Van Koten in 2000 [4] that for the first time described interesting catalytic properties of a ruthenium NCN– pincer complex for TH. In these reports, Baratta et al. described the synthesis of a novel Copyright: © 2021 by the authors. κ2 C,P − Licensee MDPI, Basel, Switzerland. class of cycloruthenated complexes bearing the anionic ( - )-[2-CH2-6-MeC6H3PPh2] δ This article is an open access article ligand. These species resulted from the reaction of the 14-electron -agostic [RuCl2{(2,6- distributed under the terms and Me2C6H3PPh2)2] complex with formaldehyde in the presence of triethylamine Via cy- conditions of the Creative Commons clometalation of an ortho-methyl group and aldehyde decarbonylation. Among the new Attribution (CC BY) license (https:// cyclometalated complexes, the derivatives 1 and 2 bearing 2-(aminomethyl)pyridine (ampy) creativecommons.org/licenses/by/ and ethylenediamine (en), respectively, were both found active for the TH of acetophenone 4.0/). (0.1 M) in isopropanol at reflux in the presence of NaOH (2 mol.%) as base and activator. Molecules 2021, 26, 4076. https://doi.org/10.3390/molecules26134076 https://www.mdpi.com/journal/molecules Molecules 2021, 26, x FOR PEER REVIEW 2 of 50 Molecules 2021, 26, 4076 2 of 45 cyclometalated complexes, the derivatives 1 and 2 bearing 2-(aminomethyl)pyridine (ampy) and ethylenediamine (en), respectively, were both found active for the TH of ace- tophenone (0.1 M) in isopropanol at reflux in the presence of NaOH (2 mol.%) as base and Whenactivator.2 (0.1 When mol.%) 2 (0.1 was mol.%) used, quantitativewas used, quantitative conversion conversion to 1-phenylethanol to 1-phenylethanol was achieved was afterachieved 30 min after reaction, 30 min whereas, reaction, when whereas,1 (0.05 when mol.%) 1 (0.05 was used,mol.%) 98% was conversion used, 98% was conversion reached inwas only reached 5 min (Schemein only 15). min Thus, (Scheme complex 1). 1Thus,(0.05 complex mol.%) was 1 (0.05 found mol.%) to be highlywas found active to for be thehighly reduction active offor a the number reduction of aryl of alkyl, a number diaryl, of and aryl dialkyl alkyl, ketonesdiaryl, and achieving dialkyl turnover ketones −1 frequenciesachieving turnover at 50% conversion frequencies (TOF at 50%50) of conversion up to 63,000 (TOF h 50and) of up turnover to 63,000 numbers h−1 and as turnover high as 9000numbers in 2 h as when high aas loading 9000 in of 2 0.01h when mol.% a loading was used of 0.01 (Scheme mol.%1). was These used Values (Scheme were 1). among These thevalues highest were reported among the in the highest literature reported at the in time the literature [4–8]. at the time [4–8]. 1 (0.05 mol%) or 2 (0.1 mol%) PPh2 PPh2 OH O NaOH (2 mol%) CO CO Ru Ru 1 2 i- 1 2 R R PrOH / 82 °C R R H2N Cl H2N Cl 0.1 M N NH2 1 2 O O O O Cl Cl Cl 1: 98% in 5 min 1: 99% in 10 min 1: 95% in 5 min 1: 98% in 10 min −1 TOF = 28,800 h−1 −1 −1 TOF50 = 60,000 h 50 TOF50 = 36,000 h TOF = 17,700 h TON = 1960 TON = 1980 TON = 1900 TON = 1960 2: > 99% in 30 min (TON up to 9000 in 2 h −1 TOF50 = 2800 h with 0.01 mol%) TON = 1000 O O O O 1: 99% in 10 min 1: 95% in 10 min 1: 99% in 15 min 1: 99% in 15 min −1 −1 −1 −1 TOF50 = 63,000 h TOF50 = 30,000 h TOF50 = 19,000 h TOF50 = 33,600 h TON = 1980 TON = 1900 TON = 1980 TON = 1980 SchemeScheme 1.1.TH TH ofof ketonesketones catalyzedcatalyzed byby thetheCP CP--cycloruthenatedcycloruthenated complexes complexes1 1and and2 2. RegardingRegarding thethe mechanism,mechanism, itit waswas postulatedpostulated byby thethe authorsauthors thatthat1 1could couldreact react with with thethe basebase toto affordafford the the corresponding corresponding amide amide complex complex thatthat could could subsequently subsequently reactreact withwith isopropanolisopropanol toto yield yield the the key key ruthenium ruthenium hydride hydride amine amine species species [9]. [Alternatively,9]. Alternatively, the latter the lattercould couldbe generated be generated through through the alkoxide the alkoxide route [10]. route Whatever [10]. Whatever the exact the route, exact the route, high thecatalytic high catalytic performance performance of 1 was of tentatively1 was tentatively ascribed ascribed to the combined to the combined presence presence of a bifunc- of a bifunctionaltional Ru–H/N–H Ru–H/N–H motif [11,12] motif [and11,12 of] anda stable of a Ru–C stable σ Ru–C-bondσ that-bond would that prevent would prevent catalyst catalystdeactivation deactivation [2]. [2]. BarattaBaratta etet al.al. recentlyrecently extendedextended thethe librarylibrary ofof ruthenacyclicruthenacyclic complexescomplexes bearingbearing thethe 2 − anionicanionic (κ(κ-2-CC,P,P)-[2-CH)-[2-CH22-6-MeC-6-MeC66HH33PPh2]]− ligandligand by by synthesizing synthesizing the seriesseries ofof dicarbonyldicarbonyl derivativesderivatives3 3––55depicted depicted in in Scheme Scheme2 [2 13[13].].The Theamine aminefree free complex complex3 3(0.1 (0.1 mol.%)mol.%) displayed displayed poorpoor activityactivity in the TH TH of of acetophenone acetophenone (0.1 (0.1 M) M) in inthe the presence presence of NaO of NaOiPr i(2Pr mol%) (2 mol%) as a asbase a base in 2-propanol in 2-propanol at reflux, at reflux, affording affording only 48% only conversion 48% conversion into 1-phenylethanol into 1-phenylethanol after 8 h afterreaction. 8 h reaction.In situ addition In situ of addition the bidentate of the ligands, bidentate en ligands,or ampy (2en equiv.),or ampy to(2 3 equiv.),dramatically to 3 dramatically increased the catalytic activity of the latter, resulting in a TOF between 1200 increased the catalytic activity of the latter, resulting in a TOF50 between50 1200 and 30,000 −1 andh−1, 30,000thus suggesting h , thus an suggesting accelerating an accelerating N–H effect upon N–H effectcoordination upon coordination to the metal to center. the metal This center.was confirmed This was by confirmed the activity by observed the activity with observed the isolated with cationic the isolated dicarbonyl cationic species dicarbonyl 4 and species5, which4 andwere5 about, which the were same about as those the sameobserved as those with observedthe in situ with generated the in 3 situ/en and generated 3/ampy 3systems,/en and 3respectively/ampy systems, (Scheme respectively 2). Similarly (Scheme to2 what). Similarly was observed to what waswith observed the neutral with mono the neutral mono carbonyl derivatives 1 and 2 [2,3], the ampy derivative 5 displayed the highest −1 −1 activity with TOF50 Values ranging between 17,000 h and 30,000 h depending on the nature of the alkali base (NaOiPr, KOH, or KOtBu). Molecules 2021, 26, x FOR PEER REVIEW 3 of 50 Molecules 2021, 26, 4076 carbonyl derivatives 1 and 2 [2,3], the ampy derivative 5 displayed the highest activity3 with of 45 TOF50 values ranging between 17,000 h−1 and 30,000 h−1 depending on the nature of the alkali base (NaOiPr, KOH, or KOtBu).