Transfer Hydrogenation Employing Ethylene Diamine Bisborane in Water and Pd- and Ru-Nanoparticles in Ionic Liquids

Herein we demonstrate the use of ethylenediamine bisborane (EDAB) as a suitable hydrogen source for transfer hydrogenation reactions on C-C double bonds mediated by metal nanoparticles. Moreover, EDAB also acts as a reducing agent for carbonyl functionalities in water under metal-free conditions.


Introduction
Hydrogenation is one of the most important chemical transformations used in academia and industry and has received notable attention in the past century [1][2][3][4][5][6][7]. It can be performed via transition metal-catalyzed activation of molecular hydrogen and is used in large-scale applications such as hydrocracking [8,9] and the Haber-Bosch-Process [10] or in medium-to lab-scale applications for the synthesis of fine and special chemicals [1][2][3]11]. However, as the use of molecular hydrogen often requires harsh reaction conditions [12] and the regio-and stereo-selectivity are challenging to control [4,5,7,13], transfer hydrogenation has evolved as useful tool for specific and highly selective hydrogenation under mild conditions [3,4,7,12,14,15]. Specifically, the use of alcohols such as ethanol,

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isopropanol, and glycerol [4,7,16,17] and also compounds like formic acid [18] or Hantzsch's ester [19] have been used as suitable hydrogen sources in transfer hydrogenation reactions. Many of these transformations can be performed by using homogenous catalysis with transition metal complexes based on iron, palladium, ruthenium, or rhodium [4,7,15,17,20,21]. In contrast, the use of non-metal based organo-catalysts has also been shown and several prolin-based catalysts are known [22,23]. A major drawback of using alcohols or other carbon-based compounds in transfer hydrogenation lies in the comparable low mass fraction of the stored hydrogen volume-to-mass ratio. For example, isopropanol delivers only one equivalent (3.3 wt-% H2) and formic acid (4.4 wt-% H2) as well. Therefore, hydrogen-rich sources for transfer hydrogenation reactions are desirable. On the other hand, amine boranes such as ammonia borane (AB) (NH3BH3) [24], methyl amine borane [24,25] (MAB), and ethylene diamine bisborane [24,26] (EDAB) have received increasing attention as hydrogen storage materials owing their hydrogen content. The mass fraction of stored hydrogen is comparably high and the compounds are easily obtained [24]. MAB releases a mass fraction of 9% H2 [25,27], EDAB a mass fraction of 10% [26], and AB a mass fraction of up to 16% H2 at a maximum temperature of 200 °C [24]. Amine boranes have not only been used as possible hydrogen storage material. Additionally, these non-toxic and water-soluble compounds have shown successful use as hydrogen sources for transfer hydrogenation reactions. AB in particular has been used elaborately for the reduction of C=C [28], C=O [29], C=N [13,30], or NO2 [13], thereby showing chemo-selectivity [13]. However, for other amine boranes, the literature is scant and little is known about chemo-, regio-, and stereo-selectivity. Our group has investigated the liberation of H2 from EDAB in ionic liquid media as a potential hydrogen storage material [26,31]. Following these studies, we focus on the use of EDAB as a possible hydrogen source for transfer hydrogenation reactions.
Referring to the ongoing debate of implementing greener processes in chemistry [32,33], but also regarding excellent behavior in catalytic conversions [34], the use of tailor-made ionic liquid media as reaction mediums has revealed encouraging effects for dehydrogenation reactions with amine boranes [26,31]. The incorporation of homogeneously dispersed metal nanoparticles as highly potent catalysts has also been demonstrated [31,[35][36][37][38][39][40][41]. Furthermore, the use of nanoparticles as catalysts for the hydrolytic dehydrogenation of AB has been shown [42][43][44][45]. Additionally, EDAB undergoes hydrolytic dehydrogenation with elevated hydrogen yields compared to the reaction in common organic solvents if ionic liquids (ILs) are implemented as reaction medium. Subsequently, transition metal nanoparticles have been used as catalysts in transfer hydrogenation reactions, reducing C=C [46] or C=O [47] functionalities. However, to the best of our knowledge, the use of nanoparticles as transfer hydrogenation catalysts in ILs as reaction media has not yet been reported. Furthermore, the use of EDAB as a suitable hydrogen source in transfer hydrogenation reactions is also unknown.

Results and Discussion
Herein we present the use of EDAB as a hydrogen source as well as the use of Pd-and Ru-NPs (NPs: nanoparticles) as suitable transfer hydrogenation catalysts for the chemo-selective hydrogenation of carbonyl functionalities and for the reduction of unsaturated carbon-carbon bonds (Scheme 1). Scheme 1. EDAB as a hydrogen source for the reduction of carbonyl functionalities and unsaturated carbon-carbon bonds.
The application of amine borane adducts as highly active bench-top reducing agents has long been known [48,49], but has fallen out of favor, and recently it has been demonstrated that they are suitable for safe reduction in pure water [50]. The reduction of carbonyl groups in different chemical surroundings is possible employing EDAB at mild temperatures and water as the solvent ( While the aromatic substrates remain intact, the reduction of α, β-unsaturated cyclohex-2-enone yields a mixture of the unsaturated cyclohex-2-enol (50% yield) and the saturated cyclohexanol (13% yield). Interestingly, the reduction of cinnamic aldehyde (Table 1, entry 5) yields solely the unsaturated cinnamic alcohol. The double bond remains unchanged, probably due to the stabilizing effect of the conjugated aromatic system. The comparison of the aliphatic carbonyl substrates octanal (Table 1, entry 6) and octan-3-one (Table 1, entry 7) reveals that aldehydes are by far more reactive toward EDAB than similar ketones. While octanal is reduced in 33%-38% yield after 1 h, only 9% of octan-3-one reacts in the same time. The yield can be notably enhanced by prolonging the reaction time to 24 h (53%). The direct comparison between octanal and 3-octanone showed that 38% 1-octanol and 9% 3-octanol are produced. A similar behavior is observed when benzaldehyde and acetophenone are reduced in direct comparison: 93% phenylmethanol and 68% 1-phenylethanol are produced. These experiments indicate that the reduction of aldehydes is faster than ketones under the given conditions.
The reduction of benzophenone yields diphenylmethanol in moderate amounts (48%-53%; Table 1, entry 8), while benzoquinone does not react under the given conditions (Table 1, entry 9). In contrast to the reduction of octan-2-one, the reduction of octan-2, 3-dione (Table 1, entry 10) yields moderate octan-2, 3-diol amounts (37%-42%). The improved reactivity might be related to the superior solubility of the dione in comparison to the single ketone. Reduction of 5-hydroxymethylfurfural (HMF) also shows only a slow conversion into furandimethanol (Table 1, entry 11; 10%). Several other functional groups are not reduced by EDAB: alkenes, aromatic double bonds, nitro groups, lactames, esters, ethers, and acids remain inert, making EDAB highly chemo-selective for the reduction of aldehydes and ketones (Table 1, entry [12][13][14][15][16]. The main influences on the yields of the reductions appear to be the solubility and the steric hindrance of the substrate. In comparison to the reduction employing ammonia borane (AB) or methyl amine borane (MAB) [50,51], reduction by EDAB is slightly slower, even at higher temperatures. The scope of substrates is very similar for all three reducing agents; a plethora of different carbonyl compounds are susceptible to reduction, leaving nearly all other functional groups intact.

General
All commercial chemicals and solvents were purchased from Sigma-Aldrich (St. Louis, MO, USA), Merck (Kenilworth, NJ, USA) and Acros (Waltham, MA, USA) and used as received. Ethylene diamine bisborane (EDAB) [26,27,31], all used ionic liquids [39,52], ruthenium nanoparticles [37], and palladium nanoparticles [39] were prepared using previously published procedures. Nuclear magnetic resonance spectroscopy was performed at 300 K using a Bruker Avance II 300 or a Bruker Avance If not otherwise indicated, all measurements were proton broad band-decoupled. The relative chemical shift δ is referenced in the remaining signal of the given deuterated solvent for 1 H and 13 C spectra. For 11 B spectra, BF3-diethylether complex was added as standard in sealed glass ampules. For 19 F spectra, trifluoromethane (δ = 0 ppm) was used as internal standard, respectively. All chemical shifts are given in parts per million (ppm). When possible, the multiplicity of each spectrum is assigned using the following abbreviations: s: singlet, d: doublet, t: triplet, q: quartet quint: quintet, sext: sextet, sept: septet, m: multiplet, br: broad signal, and mc: multiplet, centred. GC-MS was performed on an Agilent GC-system series 6890 by Agilent using a capillary column HP5MS-0. 25

Nanoparticle Synthesis
Ruthenium Nanoparticle Synthesis [35,37] The synthesis of Ru-NPs was carried out according to literature-reported procedures [35,37]. Under glove box conditions, a screw neck vial was loaded with approximately 5-15 mg of bis(2-methylallyl)(1,5-cyclooctadiene)ruthenium(II) and 0.65-1.45 mg of ionic liquid [BMMIM][NTf2] and sealed. The reaction mixture was stirred 18 h at 75 °C to yield a brown to dark brown but clear suspension. The obtained particle size averaged 2.0 nm with a size distribution of ± 0.5 nm [35,37]. Palladium Nanoparticle Synthesis [39] The synthesis of Pd-NPs was carried out according to a literature-reported procedure [39]. A screw neck vial was loaded with approximately 3 mg of palladium(II)acetate and 600 mg of ionic liquid [(BCN)MIM][NTf2] and sealed. The reaction mixture was stirred 3 h at 130 °C to yield an orange but clear suspension. The obtained particle size averaged 7.1 nm with a size distribution of ± 2.2 nm [39].

Metal-Free Transfer Hydrogenation in Water
Exemplary procedure (Table 1; entry 2): A vial was charged with 2.3 mmol acetophenone (Table 1) and 5 mL demineralized water. After adding 0.5 mmol of EDAB (four H2 equivalents), the vial was sealed, placed in an aluminum heating block at 80 °C, and the mixture was stirred for the given time (Table 1). Subsequently, the aqueous suspension was cooled down and extracted three times with 5 mL Et2O. The organic layers were combined and the solvent was removed under reduced pressure. The product yield was determined by NMR spectroscopy using a defined amount of Si2Me6 as internal standard.

Transfer Hydrogenations in Ionic Liquids with Metal Nanoparticles
Exemplary procedure (Table 2; entry 1): In a typical transfer hydrogenation experiment, a vial was charged with the ruthenium nanocatalyst mixture of previously synthesized ruthenium nanoparticles (3 mg Ru) in ionic liquid (1.28 g; Ru@BMMIM][NTf2]) [37] and 9 mmol cyclohexene. Subsequently, 1.7 mmol EDAB was added and the vial was sealed. The reaction mixture was stirred overnight at 70 °C and then cooled to room temperature. A defined amount of CDCl3 as solvent and hexamethyl disilane (HMDS; Si2Me6) as internal standard was added to the mixture and homogenized. A sample was taken and the product yield was determined by NMR spectroscopy (Tables 2 and 3). The Pd-catalyzed reactions used 600 mg [(CN)BMIM][NTf2] and 0.5 mg Pd nanoparticles prepared as previously published [39].

Conclusions
In summary, ethylenediamine bisborane (EDAB) is a suitable hydrogen source for transfer hydrogenation reactions on C-C double bonds mediated by metal nanoparticles. Several organic model compounds could be shown to undergo reduction in the presence of the Ru-system as well as the Pd-system. In most cases, the latter showed considerably higher activity. The single hydrogenation of triple bonds yields only Z-isomeric compounds, as expected in a heterogeneous catalytic reaction. C-N triple bonds (nitriles) are not susceptible to the reduction. C-O double bonds can be reduced without the presence of metal particles in water. C-C double bonds can be readily reduced, while aromatic double bonds remain inert. In future investigations, the selectivity, time-resolved studies, and solvent effects will be addressed. The reduction with this air-and moisture-stable amine borane adduct could complement the synthetically interested chemist's toolkit.