Article pubs.acs.org/OPRD
Cite This: Org. Process Res. Dev. XXXX, XXX, XXX−XXX
SNS-Ligands for Ru-Catalyzed Homogeneous Hydrogenation and Dehydrogenation Reactions Johannes Schörgenhumer,† Axel Zimmermann,*,‡ and Mario Waser*,† †
Institute of Organic Chemistry, Johannes Kepler University Linz, Altenbergerstr. 69, 4040 Linz, Austria Patheon Austria, part of Thermo Fisher Scientific, St. Peterstr. 25, 4020 Linz, Austria
‡
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ABSTRACT: A detailed study of literature-known and novel S-containing pincer-type ligands for ruthenium-catalyzed homogeneous hydrogenation and dehydrogenation reactions was carried out. The scope and limitations of these catalysts were carefully investigated, and it was shown that simple bench-stable SNS−Ru complexes can be used to facilitate the hydrogenation of a variety of different substrates at a maximum H2 pressure of 20 bar under operationally simple, easy to scale up, gloveboxfree conditions by using starting materials and reagents that do not require any special purification prior to use. It was also shown that such complexes can be used to catalyze the dehydrogenative coupling of alcohols and amines to get amides as well as for the dehydrogenative dimerization of alcohols to esters.
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Gusev’s SNS-based catalyst IIa.8 This catalyst has shown very good activity for ester hydrogenations at 50 bar, and we were surprised to see that this complex has not been more frequently used since that impressive first report. Literature research revealed that in general SNS and SNN pincer-type ligands have not received that much attention to date, which came as a surprise to us considering the simple synthesis of some of these ligands.8 We therefore became interested in testing this platform for its potential to meet the abovementioned criteria (i.e., lower hydrogenation pressure and robust and operationally simple “glovebox-free” conditions that may allow for industrial use) and carried out broad and systematic testing of different catalyst derivatives and conditions for homogeneous hydrogenations (i.e., of esters, Scheme 1, top reaction). In addition, the groups of Gusev and Yang also carried out detailed mechanistic studies for this catalyst,8,11 and Gusev also described the potential of their catalyst for the oxidative dimerization of EtOH to EtOAc.8,11a,b Surprisingly, to the best of our knowledge this is the only thoroughly investigated example of an acceptorless dehydrogenation reaction with SNS-containing pincer-type ligands to date.12 We therefore also carried out a series of different dehydrogenation experiments within this study (Scheme 1, lower reactions). Altogether, we now wish to provide a detailed overview of the potential, robustness, and limitations of ruthenium complexes containing different sulfur-based pincertype ligands for different homogeneous hydrogenation and dehydrogenation reactions that may also hold promise eventually for larger-scale applications.
INTRODUCTION The homogeneous hydrogenation of carboxylic acid derivatives, i.e. esters, is a transformation of utmost importance.1 Accordingly, the development of catalyst systems to carry out these reactions under mild and environmentally benign conditions is at the forefront of catalysis research, and a variety of different approaches relying on different metals and ligands have been introduced over the past decade.1−10 Tridentate pincer-type ligands have emerged as one of the most important general structural platforms for homogeneous transition metal catalysis.2 Pioneering work by Milstein3 and others,4 who introduced highly active Ru-based PNN or PNP pincer systems, inspired the development of a variety of Rubased catalysts and led to several impressive applications for homogeneous hydrogenation reactions of carboxylic acid derivatives.5 In addition, the last years have witnessed an increasing interest in the replacement of noble metals by cheaper, more abundant base transition metals such as Mn and Fe. These catalyst systems can also be used for robust hydrogenations of esters and other functional groups, although they usually require higher catalyst loadings than the noblemetal-based systems.6 With respect to potential larger-scale industrial (ester) hydrogenations, the use of highly active homogeneous Ru catalysts represents an attractive opportunity. Herein some of the main requirements are low catalyst loadings; cheap ligands; operationally simple, scalable, and robust conditions avoiding glovebox procedures; and H2 pressures below 20 bar, allowing hydrogenations to be performed in standard multipurpose batch vessels. One catalyst system that fulfils a lot of these requirements and has proven its potential on a multiton scale is Takasago’s Ru-MACHO complex I, which can even be used for the atmosphericpressure hydrogenation of esters when an additional Nheterocyclic carbene (NHC) ligand is used (although higher loadings are required).7 A different class of Ru complexes that has shown very promising catalytic potential in the initial investigations is © XXXX American Chemical Society
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RESULTS AND DISCUSSION Ligands Synthesized and Tested. We started our investigations by preparing13 a variety of easily accessible SNS complexes II in analogy to Gusev’s work (Scheme 2).8 In Received: May 3, 2018 Published: June 8, 2018 A
DOI: 10.1021/acs.oprd.8b00142 Org. Process Res. Dev. XXXX, XXX, XXX−XXX
Organic Process Research & Development
Article
and 5). Reactions carried out at different concentrations then revealed a pronounced sensitivity of this system. While neat reactions performed well (entry 6), we were not able to identify reproducible and robust conditions at higher dilutions (0.1 M), as the conversions varied between almost zero up to 80−90% from experiment to experiment under identical conditions (0.1 M concentration of 1a, 10 bar H2, 0.1 mol % IIa, 10 mol % t-BuOK, 80−100 °C). We carried out a broad variety of experiments (different qualities of solvents, base, etc.) to understand the reasons for these seemingly random outcomes, but in the end we were able to achieve good and reliable conversions under these conditions only when we used a larger amount of base and a longer reaction time (entry 7). Having shown that in general the hydrogenation of 1a at 10 bar is possible with reasonable conversion when working at temperatures between 80 and 100 °C, we next tested the potential of additives to improve the performance and also to make the whole procedure more robust (i.e., with respect to the above-mentioned concentration sensitivities). It was recently shown for Ru-MACHO-catalyzed ester hydrogenations that the addition of carbenes results in a highly active system that even operates at 1 atm H2 (although higher catalyst and base loadings are required compared with highpressure autoclave conditions).7b Unfortunately, upon investigating the applicability and potential of this strategy for SNS systems, we observed clearly reduced catalytic performance (Table 1, entry 8), and the same detrimental effect was observed upon addition of NaBH4 (entry 9) (this effect was also present when working at higher pressures). Unfortunately, we do not have a convincing (experiment- and/or analysisbased) explanation for why addition of these additives has such a negative effect on the reaction with Ru−SNS-based complexes compared with the Ru-MACHO system, as we could not isolate or analyze the complex originating from the addition of the NHC to the catalyst (which would give insight if, for example, one of the labile S ligands was cleaved off or the new complex was sterically too crowded to allow for facile substrate coordination). Nevertheless, our experiments under 10 bar H2 have unambiguously proven that the standard Gusev catalyst system IIa is a potentially effective ester hydrogenation catalyst under glovebox-free conditions. However, it should be clearly pointed out that sometimes only minor changes of the reaction parameters can significantly reduce the conversion rate and may lead to less robust and less reproducible outcomes (i.e., under higher dilution). To establish a slightly more robust procedure, we next carried out further investigations under a higher H2 pressure (20 bar; Table 1, entries 10−16). It was clearly shown that under these conditions the hydrogenation proceeds at a higher rate, and we could reach almost complete conversion at 80 °C after 5 h (entry 10). Again, lowering the catalyst loading reduced the rate measurably (entry 11). Interestingly, it seems that the reaction slows down with increasing conversion/time, as we noted rather fast product formation after 1 h already (75% conversion; entry 12) but another 4 h was needed to reach almost complete product formation. When we tested different bases, we found that others allow for reasonable reaction rates too (entries 13−16), but not as high as with t-BuOK. With high-yielding conditions established (entry 10), we then put our focus on the screening of the different catalysts shown in Scheme 2. We first tested the Gusev-type systems II and found that the dimethyl-containing complex IIb is even slightly more reactive than the diethyl-
Scheme 1. Targeted Investigations of Ru−SNS Systems for Hydrogenations and Dehydrogenations
Scheme 2. Ru Complexes with S-Containing Pincer-Type Ligands Tested in This Study
addition to these simple aliphatic ligand systems, we also decided to investigate pyridine-based SNS complexes III14 as well as the analogous SCS complexes IV.15 Besides these symmetric systems, we also synthesized a variety of dissymmetric S-containing pincer ligands to access the pyridine-based complexes V−VIII within this study.16 Homogeneous Hydrogenation. To elucidate the catalytic potential of the S-containing catalyst systems shown in Scheme 2 for homogeneous hydrogenation reactions under a maximum H2 pressure of 20 bar, we first tested them for the hydrogenation of methyl benzoate (1a) under a variety of different conditions (Table 1). In all of these reactions, we used dry, degassed toluene as the solvent (unless otherwise stated), and the catalysts and reagents were weighed, handled, and charged avoiding any glovebox conditions. The first experiments were carried out using the parent Gusev system IIa at 10 bar (entries 1−9). When 0.1 mol % of the catalyst was used, we observed almost 40% conversion after 5 h at 60 °C, and the reaction rate could be significantly improved by raising the reaction temperature to 100 °C (entries 1−3). Unfortunately, when the catalyst loading was lowered stepwise to 0.02 mol % under otherwise identical conditions, we observed a dramatic decrease in the reaction rate (entries 4 B
DOI: 10.1021/acs.oprd.8b00142 Org. Process Res. Dev. XXXX, XXX, XXX−XXX
Organic Process Research & Development
Article
Table 1. Catalyst Screening and Identification of Robust Conditions for the Hydrogenation of Methyl Benzoate (1a)
entrya
cat. (mol %)
base (mol %)
T [°C]
PH2 [bar]
t [h]
conv. [%]b
1 2 3 4 5 6c 7d 8e 9f 10 11 12 13 14 15 16 17 18h 19i 20 21 22 23 24 25 26 27 28 29 30 31 32 33
IIa (0.1%) IIa (0.1%) IIa (0.1%) IIa (0.05%) IIa (0.02%) IIa (0.1%) IIa (0.5%) IIa (0.1%) IIa (0.1%) IIa (0.1%) IIa (0.05%) IIa (0.1%) IIa (0.1%) IIa (0.1%) IIa (0.1%) IIa (0.1%) IIb (0.1%) IIb (0.1%) IIb (0.1%) IIc (0.1%) IId (0.1%) IIIa (0.1%) IIIb (0.1%) IIIc (0.1%) IIId (0.1%) IVa (0.1%) IVb (0.1%) V (0.1%) VI (0.1%) VIIa (0.1%) VIIb (0.1%) VIII (0.1%) I (0.1%)
t-BuOK (10%) t-BuOK (10%) t-BuOK (10%) t-BuOK (10%) t-BuOK (10%) t-BuOK (10%) t-BuOK (50%) t-BuOK (10%) t-BuOK (10%) t-BuOK (10%) t-BuOK (10%) t-BuOK (10%) NaOMe (10%) NaH (10%) KOH (10%) Cs2CO3 (10%) t-BuOK (10%) t-BuOK (10%) t-BuOK (10%) t-BuOK (10%) t-BuOK (10%) t-BuOK (10%) t-BuOK (10%) t-BuOK (10%) t-BuOK (10%) t-BuOK (10%) t-BuOK (10%) t-BuOK (10%) t-BuOK (10%) t-BuOK (10%) t-BuOK (10%) t-BuOK (10%) t-BuOK (10%)
60 80 100 100 100 100 80 80 80 80 80 80 80 80 80 80 80 80 100 80 80 80 80 80 80 80 80 80 80 80 80 80 80
10 10 10 10 10 10 10 10 10 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20
5 5 5 5 5 5 20 5 5 5 5 1 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5
38 78 97 54 12 93 95 19 36 97 65 75 50 88 63 78 100 (96g) 78 89 61 19 3
