Backbone-functionalised ruthenium diphosphine complexes for catalytic upgrading of ethanol and methanol to iso-butanol †

E ﬃ cient catalysts for Guerbet-type ethanol/methanol upgrading to iso-butanol have been developed via Michael addition of a variety of amines to ruthenium-coordinated dppen (1,1-bis(diphenylphosphino) ethylene). All catalysts produce over 50% iso-butanol yield with >90% selectivity in 2 h with catalyst 1 showing the best activity (74% yield after this time). The selectivity and turnover number approach 100% and 1000 respectively using catalyst 6 . The presence of uncoordinated functionalised donor groups in these complexes results in a more stable catalyst compared to unfunctionalised analogues.


Introduction
The gradual move from gasoline to either pure biofuels or biofuel blends is a significant contribution towards environmental sustainability and fuel security. 1,22][3][4] Bioethanol has long emerged as an alternative to gasoline but is associated with some drawbacks: its energy density is relatively low (around 70% gasoline energy density), it can easily retain water leading to separation and dilution problems in engine tanks and has a proven tendency to corrode existing engine technology and fuel infrastructure. 5,6By contrast, higher molecular weight alcohols such as n-butanol, possess similar fuel properties to conventional gasoline and are often termed "advanced biofuels"; for example, the energy density of n-butanol is about 90% that of gasoline, it is not miscible with water and not corrosive. 7The branched isomer iso-butanol has even more compatible fuel properties (98% gasoline energy density) relative to n-butanol and with the application of these advanced biofuels many of the ethanol limitations can be overcome. 8Butanols can be produced through both biological and chemical processes.The biological process, ABE fermentation, involves the use of strains of the bacterium Clostridium acetobutylicum to produce mixtures of acetone, butanol and ethanol. 9,10Though known to be sustainable, there are technological issues associated with the ABE process such as low yield (1-2%), separation issues and the high cost of fermentation substrates (molasses), 7,11,12 making the bulk synthesis of biobutanol a challenge.][15][16] Guerbet chemistry has emerged as a promising approach to n-butanol production as it can be based on renewable bioethanol. 171][22][23] In this reaction, C-C bonds are formed from alcohol substrates by means of so-called "borrowed hydrogen" chemistry. 24The reaction pathway includes dehydrogenation of simple alcohol, base-catalyzed aldol condensation reaction and rehydrogenation of the aldol product. 25Our group [26][27][28][29][30][31][32][33] and others [34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49] have been seeking new homogeneous catalysts for ethanol upgrading via Guerbet chemistry.Despite these recent advances, there is still significant scope for further catalyst development.
Despite the growing number of ruthenium-phosphine catalysts (Fig. 1, I-III) 29 and the interest in related first row transition metal catalysts (IV), 40,41 the small-bite angle bis(diphenylphosphino)methane (dppm) catalyst (I) that was among our first reported catalysts remains a benchmark in terms of overall performance for the conversion of ethanol and methanol to iso-butanol (Scheme 1).We were therefore interested in expanding this catalyst family, particularly to include pendent functional groups which may improve catalyst solubility in alcohol/water, improve catalyst stability and potentially act as internal bases.

Synthesis of ruthenium complexes
We identified that Michael-type addition to the commercially available diphosphine 1,1-bis(diphenylphosphino)ethylene (dppen) could be a versatile route to a range of backbone-functionalised ligands with nominally the same bite angle as the parent dppm ligand.1][52][53] This route is elegant in that it escapes the need to protect the phosphine moieties, the ruthenium dichloride fragment itself acting as a protecting group (and potentially also activating the olefin towards nucleophilic attack).5][56][57][58][59][60][61][62] Complexes 1-7 were synthesized as yellow solids in goods yields (typically >80%) and characterised by NMR spectroscopy, mass spectrometry and X-ray crystallography.The 31 P NMR spectrum of the trans-[RuCl 2 (dppen) 2 ] (Pre-Cat) gave a singlet at 15.3 ppm which upon functionalisation with these amines shifted upfield to ca. 11 ppm apart from 6 which gave a peak at 15.9 ppm.In addition to the peak at 11 ppm, 5 displayed another chemical shift at −20.8 ppm corresponding to the uncoordinated pendent PPh 2 group.In the 1 H NMR spectra, the quintet at 6.1 ppm for the parent trans-[RuCl 2 (dppen) 2 ] methylidene proton (CvCH 2 ) moved to a resonance around 3 ppm in all the complexes, signifying methylene protons along with a newly formed methine proton around 5 ppm.The ESI mass spectra of complexes 1-7 corresponded to the expected chemical structures (see ESI † for further experimental details).
Single crystals of 1, 3, 4 and 7 were obtained by slow diffusion of pentane into fluorobenzene/benzene solutions of the complexes.Fig. 2 shows the molecular structures of 1 (a), 3 (b), 4 (c) and 7 (d) with selected bond lengths and angles in Table 1.All crystallographic data are given in the ESI.† All complexes displayed octahedral geometry with trans chlorides.The parent complex trans-[RuCl 2 (dppm) 2 ] has a P-Ru-P angle of 72°. 63The analogous angles for 1, 3, 4 and 7 are the same within error; similarly, Ru-P and Ru-Cl distances are within the expected range (Table 1). 51,63,64talytic activity Complexes 1-7 were tested for ethanol/methanol to isobutanol catalysis using the standard conditions we have reported previously; 28,29 the results are shown in Table 2.In general, all catalysts performed well with over 50% yield and 90% selectivity in 2 h.Catalyst 1 with diamine ethylene functionalities gave 74% yield and 78% ethanol conversion in 2 h (Table 2, run 1).This compares favorably to the previous best catalyst trans-[RuCl 2 (dppm) 2 ] (65% yield, 98% selectivity and 88% conversion).Whilst it can be challenging to benchmark more widely against other literature systems where specific attributes (e.g.32][33]39,43 Catalyst 2 with the same amine functionality but a longer propylene linker showed lower activity towards iso-butanol (59% yield).The sequence 1, 6, 7 where only the functional group is varied from -NH 2 to -SH to -OH has similar performance for 1 and 7 but catalyst 6 shows exceptionally high selectivity within the liquid phase with iso-butanol being the only product observed by GC.Extending the run time to 20 hours in most cases gave near quantitative conversion of ethanol.
Scheme 1 Catalytic pathway for the Guerbet reaction of ethanol and methanol to iso-butanol. 29heme 2 Synthesis of complexes 1 to 7.
Fig. 1 Previously used ruthenium and manganese phosphine-based catalysts for conversion of ethanol and methanol to iso-butanol.
Any discrepancy between conversion and product yield comes from small amounts of solid byproducts, consisting of a mixture of sodium carbonate, formate and acetate as observed in previous studies. 29he reason for the improved performance of the current catalysts is not definitive at this stage.The obvious reason is a subtle change to catalyst sterics and electronics.We have no NMR spectroscopic evidence for any interaction between the pendent donor groups and ruthenium centre.Some complexes (e.g. 1, 2, 6, and 7) have the possibility for deprotonation during the basic conditions of catalysis to act as an internal base but other complexes where this is less likely (e.g. 3 and 4) have similar performance.Catalyst 6 with a -SH group has the best performance, certainly in terms of selectivity, suggesting this potentially softer donor group may play an enhanced role in either coordination or deprotonation.
This enhanced stability during catalysis could be due to stabilisation of kinetically fragile intermediates by the pendent groups or, more prosaically, these pendent groups improving catalyst solubility in mixed alcohol/water solvents.

Conclusions
Backbone-functionalised ligands based on the dppm motif can be accessed by addition various nitrogen nucleophiles to trans-[RuCl 2 (dppen) 2 ], in which the transition metal acts as a protecting group as well as the active catalyst centre.The performance of these complexes as catalysts in the Guerbet upgrading of methanol/ethanol to iso-butanol matches or exceeds that of the parent trans-[RuCl 2 (dppm) 2 ], largely due to enhanced stability of these catalysts in standard reaction conditions.This methodology of catalyst derivation has potential to further diversify ligand libraries and offer a potential route to catalyst heterogenisation.

Experimental section
More details of complex synthesis, procedures for performing the catalytic experiments and characterizing data can be found in the ESI.†

General considerations
All procedures were carried out under an inert atmosphere (N 2 ) using standard Schlenk line techniques or in an inert atmosphere glovebox (Ar).Chemicals were purchased from the usual suppliers and used without further purification.Anhydrous ethanol and methanol were purchased from Sigma-Aldrich and used as received.Pentane and deuterated solvents were dried using established procedures and further degassed under nitrogen.Other solvents were purified using an Anhydrous Engineering Grubbs-type solvent system.

Synthesis of complexes
Pre-Cat, trans-[RuCl 2 (dppen) 2 ], was synthesised using a literature method. 50,51Complexes 2-4 have been synthesised previously and were prepared by slight modifications of the literature procedures. 50,51Novel complexes 1 and 5-7 were synthesised by adaptations of the same literature method.

Catalysis
Catalytic runs were carried out in a sealed 100 mL Parr stainless steel autoclave with an aluminium heating mantle and using magnetic stirring.A typical procedure using Pre-Cat is given below.
Pre-Cat, trans-[RuCl 2 (dppen) 2 ], (0.0165 g, 0.0171 mmol, 0.1 mol%), NaOMe (1.85 g, 34.26 mmol, 200 mol%) and a stirrer bar were added to a clean oven dried fitted PTFE insert inside a glove box.The insert was sealed within a 100 mL Parr stainless steel autoclave which was then transferred to a nitrogen/vacuum manifold.Methanol (10 mL, 247.13 mmol) and ethanol (1 mL, 17.13 mmol) were injected into the autoclave through an inlet against a flow of nitrogen.The autoclave was sealed and placed into a pre-heated (180 °C) aluminium heating mantle and stirred at 500 rpm.After the reaction run time (2 h), the autoclave was cooled to room temperature in an ice-water bath.The autoclave was carefully vented to remove any gas generated during the reaction.A liquid sample was  removed, filtered through a short plug of (acidic) and by GC (100 μL of sample, 25 μL of hexadecane standard, 1.7 mL diethyl ethersample filtered through a glass filter paper to remove insoluble salts).

a
Conditions: ethanol (1 mL, 17.13 mmol), methanol (10 mL, 247.13 mmol), [Ru] catalyst (0.01713 mmol, 0.1 mol%), NaOMe (34.26 mmol, 200 mol%), mol% is based on ethanol substrate, 180 °C.b Total conversion of ethanol as determined by GC analysis of the liquid phase.c Total TON based on mmol of total ethanol converted to products per mmol of [Ru] catalyst (ethanol equivalent relative to mmol of catalysts × conversion = 1000 × conversion).d TON based on mmol of any product formed per mmol [Ru] catalyst (ethanol equivalent relative to mmol of catalysts × product yield = 1000 × product yield).e Total yield and selectivity of alcohol products in the liquid fraction as determined by GC. f Catalyst I = trans-[RuCl 2 (dppm) 2 ].Paper Dalton Transactions Dalton Trans.This journal is © The Royal Society of Chemistry 2024 Open Access Article.Published on 05 April 2024.Downloaded on 4/24/2024 10:15:28 AM.This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.

Table 2
Ruthenium catalysed conversion of ethanol and methanol to iso-butanol d (yield) e [selectivity] e (%)