The Synthesis, Characterization and Reactivity of a Series of Ruthenium N-triphosPh Complexes

Summary

Ruthenium phosphine complexes are widely used for homogeneous catalytic reactions such as hydrogenations. The synthesis of a series of novel tridentate ruthenium complexes bearing the N-triphos ligand N(CH₂PPh₂)₃ is reported. Additionally, the stoichiometric reaction of a dihydride Ru–N-triphos complex with levulinic acid is described.

Abstract

Herein we report the synthesis of a tridentate phosphine ligand N(CH₂PPh₂)₃ (N-triphos^Ph) (1) via a phosphorus based Mannich reaction of the hydroxylmethylene phosphine precursor with ammonia in methanol under a nitrogen atmosphere. The N-triphos^Ph ligand precipitates from the solution after approximately 1 hr of reflux and can be isolated analytically pure via simple cannula filtration procedure under nitrogen. Reaction of the N-triphos^Ph ligand with [Ru₃(CO)₁₂] under reflux affords a deep red solution that show evolution of CO gas on ligand complexation. Orange crystals of the complex [Ru(CO)₂{N(CH₂PPh₂)₃}-κ³P] (2) were isolated on cooling to RT. The ³¹P{¹H} NMR spectrum showed a characteristic single peak at lower frequency compared to the free ligand. Reaction of a toluene solution of complex 2 with oxygen resulted in the instantaneous precipitation of the carbonate complex [Ru(CO₃)(CO){N(CH₂PPh₂)₃}-κ³P] (3) as an air stable orange solid. Subsequent hydrogenation of 3 under 15 bar of hydrogen in a high-pressure reactor gave the dihydride complex [RuH₂(CO){N(CH₂PPh₂)₃}-κ³P] (4), which was fully characterized by X-ray crystallography and NMR spectroscopy. Complexes 3 and 4 are potentially useful catalyst precursors for a range of hydrogenation reactions, including biomass-derived products such as levulinic acid (LA). Complex 4 was found to cleanly react with LA in the presence of the proton source additive NH₄PF₆ to give [Ru(CO){N(CH₂PPh₂)₃}-κ³P{CH₃CO(CH₂)₂CO₂H}-κ²O](PF₆) (6).

Introduction

Ruthenium phosphine based complexes are some of the most widely studied and chemically versatile molecular catalysts.^1-9 Typically, such ruthenium catalysts contain either mono- or bi-dentate ligands that dictate the electronics, sterics, geometry and solubility of the complex, and which profoundly impact on catalytic activity. Multidentate phosphine systems have been less widely studied for catalysis, as they are known to impart greater stability on the metal center owing to the greater chelate effect of multiple phosphorus donors on the metal center. Such stabilization can be undesirable for catalysis, however, under harsher reaction conditions (higher temperatures and pressures) the complex stabilizing properties of such ligands can be advantageous in ensuring catalyst integrity. One such multidentate phosphine ligand system that we^10-12 and others^13-18 have investigated for imparting complex stability and facial coordination geometries is the so-called N-triphos ligand series where three phosphine arms are attached to an apical bridging nitrogen atom forming a potentially tridentate ligand. One of the key features to these particular ligands is the facile way that they can be synthesized via a phosphorus based Mannich reaction from readily available secondary phosphines (Figure 1), hence phosphines with a variety of R-groups can be prepared usually in high yields and with minimal work-up. The overall goal of this methodology is to present a facile route by which ruthenium dihydride complexes featuring N-triphos ligands can be accessed for subsequent catalytic applications. Recently, Ru-triphos based complexes have attracted attention as catalysts for the hydrogenation reactions of biomass derived products, such as levulinic acid,^19,20 bio-esters^11,21 and carbon dioxide²² to higher value chemicals. It would be advantageous to expand the scope of Ru-triphos derivatives that are either as, or more active than the systems already reported, especially if they are synthetically easier to access, such as the N-triphos ligand. The most studied carbon-centered analogue typically suffers from low yielding synthesis and involves highly air-sensitive metal phosphide reagents, unlike the N-triphos ligand, which is more adaptable and easier to prepare.^10-18

N-triphos ligands remain relatively under-investigated, with only molybdenum, tungsten, ruthenium, rhodium and gold complexes having been reported from nine publications. This is in stark contrast to the boron- and carbon-centered analogues, for which there are around 50 and 900 articles, respectively, with a great number of unique compounds. Nonetheless, N-triphos containing complexes have found application in the asymmetric catalytic hydrogenation of pro-chiral olefins²³ as well as asymmetric cyclohydroamination of N-protected γ-allenyl sulfonamides.²⁴ Additionally, a ruthenium complex coordinated by a bulky N-triphos ligand featuring phospholane coordinating moieties was found to activate silanes, a key step in the development of organosilicon chemistry.²⁵

As part of the ongoing research program in catalysis, we sought to prepare a range of ruthenium N-triphos^Ph precatalysts and to investigate their stoichiometric reactions and catalytic potential. Despite molybdenum complexes of N-triphos^Ph having first been reported over 25 years ago, their application, catalytic or otherwise has not been investigated. This work demonstrates the applicability of the N-triphos scaffold, which despite being generally underdeveloped, possess many desirable features such as complex stability. Herein we report the synthetic route and characterization of to a series of ruthenium N-triphos^Ph complexes that may find application in catalytic hydrogenation reactions.

Protocol

Note: Carry out all syntheses in a fume hood, and only after appropriate safety issues have been identified and measures taken to protect against them. Personal protective equipment include a lab coat, gloves and safety goggles and should be worn at all times.

1. Synthesis of N,N,N-tris(diphenylphosphinomethylene)amine, N(CH₂PPh₂)₃ (N-triphos^Ph) (1)

1. To a 200 ml oven dried Schlenk flask add diphenyl(hydroxymethylene)phosphonium chloride¹¹ (6.99 g, 24.7 mmol) and place under nitrogen via three sequential vacuum-nitrogen cycles on a dual-manifold Schlenk line.
2. Add degassed methanol (30 ml) and triethylamine (9.5 ml, 68.1 mmol), and stir at RT for 1 hr to ensure conversion of the phosphonium chloride salt to the hydroxymethene phosphine. Next, add degassed ammonia solution in methanol (2 M, 4.1 ml, 8.2 mmol).
3. Heat the reaction mixture for 2 hr under reflux, during which the ligand will precipitate out as a white solid.
4. Although the N-triphos^Ph ligand is stable to oxidation in air over short periods of time, for optimal purity, remove the solvent via cannula filtration²⁶ under nitrogen, and rinse with degassed methanol (3 x 10 ml) to obtain an analytically pure product, and store under a nitrogen atmosphere.

2. Synthesis of [Ru(CO)₂{N(CH₂PPh₂)₃}-κ³P] (2)

1. To a 200 ml oven dried Schlenk flask, add N-Triphos^Ph (1.0 g, 1.63 mmol) and [Ru₃(CO)₁₂] (347 mg, 0.54 mmol), and place under nitrogen via three sequential vacuum-nitrogen cycles on a dual-manifold Schlenk line.
2. Add 30 ml of dry, degassed toluene and bring the mixture to reflux for 12 hr.
3. After this 12 hr reflux, filter the solution via cannula to a second Schlenk flask to remove small amounts of metallic ruthenium that form during the course of the reaction.
4. Reduce the volume of solvent to approximately 10 ml under vacuum using a dual-manifold Schlenk line fitted with a liquid nitrogen cooled trap, to induce precipitation of the complex.
5. Recrystallize the precipitate by heating gently (80–90 °C) in an oil bath until complete redissolution occurs, and subsequent slow cooling to RT by removing the heat from the oil bath, but allowing the Schlenk flask to remain submerged. Leave O/N to give an orange crystalline solid.
6. Isolate the orange crystals suitable for X-ray diffraction via cannula filtration of the supernatant into another oven dried Schlenk flask. Next, rinse the crystals with dry and degassed toluene (2 x 5 ml) and dry in vacuo O/N. Save the combined supernatant and washings in a separate Schlenk flask.
7. Obtain a second batch of crystals from the combined supernatant and rinsing solutions by a similar recrystallization process to steps 2.5 and 2.6 to improve the overall yield of reaction.
8. Store the complex under nitrogen as exposure to air leads to the slow conversion to the oxidized carbonate complex (see below).

3. Synthesis of [Ru(CO₃)(CO){N(CH₂PPh₂)₃}-κ³P] (3)

1. To a 200 ml Schlenk flask, add 2 (280 mg, 0.364 mmol) and 5 ml of toluene to generate a partially dissolved orange suspension.
2. Insert a needle attached to a balloon of oxygen into the suspension and bubble oxygen at a rate of 2–3 bubbles per second through the reaction mixture for 10 min.
3. As an orange precipitate forms, collect it by filtration in air and washed with toluene (2 x 5 ml) and diethyl ether (2 x 5 ml) and dry in vacuo to give a free flowing orange powder that was stable in air.
4. In order to grow crystals suitable for X-ray diffraction, dissolve 100 mg of 3 in 3 ml dichloromethane in a vial and layer 3 ml toluene on top by slowly allowing this solvent to run down the side of the vial.
   1. Leave this O/N to obtain crystals. Isolate the crystals by decanting the supernatant, and washing the toluene (2 x 3 ml) and diethyl ether (2 x 3 ml). Dry in vacuo on a dual-manifold Schlenk line.

4. Synthesis of [Ru(H)₂(CO){N(CH₂PPh₂)₃}-κ³P] (4)

1. Prepare a solution of 3 (763 mg, 0.953 mmol) in 20 ml of dry, degassed THF and inject into a 100 ml Autoclave Engineer’s high-pressure reactor under a positive pressure (0.2 bar) of nitrogen.
2. Change the reactor head space gas to 100% hydrogen and pressurize to 15 bar at RT, then heat to 100 °C with stirring for 2 hr.
   Caution! Ensure all safety procedures have been adhered to when using high pressure systems!
3. After cooling to RT, carefully vent the excess hydrogen gas in the reactor head space and change to nitrogen.
4. Transfer the reaction solution to a 100 ml Schlenk flask under nitrogen and, after reconnecting to a dual-manifold Schlenk line, filter via cannula and dilute with 20 ml of dry, degassed methanol.
5. Remove the solvent under vacuum using a dual-manifold Schlenk line fitted with a liquid nitrogen cooled trap to give an orange powder. Wash this orange powder with dry, degassed methanol (3 x 5 ml) and dry, degassed diethyl ether (3 x 5 ml) and dry in vacuo.
6. Grow crystals suitable for X-ray diffraction analysis O/N from a saturated dry and degassed toluene solution of 4 layered with an equivolume amount of dry, degassed methanol.
7. Store the complex under nitrogen.

5. Reaction of [RuH₂(CO){N(CH₂PPh₂)₃}-κ³P] (4) with NH₄PF₆ and Levulinic Acid

1. Prepare a solution of 4 (48.4 mg, 65.2 μmol) in 2 ml dry, degassed toluene in a oven dried Schlenk flask, and add via syringe to a stirred solution of NH₄PF₆ (10.6 mg, 65.0 μmol) in acetonitrile (2 ml) in a separate oven dried Schlenk flask.
2. Stir the reaction mixture at RT for 2 hr. After, remove the solvent in vacuo using a dual-manifold Schlenk line fitted with a liquid nitrogen cooled trap to give the intermediate complex [RuH(CO)(MeCN){N(CH₂PPh₂)₃}-κ³P] (5).
3. Wash with dry, degassed hexane (3 x 3 ml) and dry in vacuo to isolate complex 5 as a brown powder.
4. To a solution of 5 in 0.5 ml degassed acetone-d₆, add levulinic acid (10.8 mg, 93.0 μmol, 1.43 equiv.) in 0.5 ml of degassed acetone-d₆. Stir the reaction mixture for 2 min using a vortex stirrer.
5. Record ¹H and ³⁰P{¹H} NMR spectra of the reaction every hour for 16 hr to observe the reaction.²⁷

Results

The N-triphos^Ph ligand (1) and the ruthenium complex series: Ru(CO)₂{N(CH₂PPh₂)₃}-κ³P] (2), [Ru(CO₃)(CO){N(CH₂PPh₂)₃}-κ³P] (3) and [Ru(H)₂(CO){N(CH₂PPh₂)₃}-κ³P] (4) were characterized via ¹H, ¹³C{¹H}, ³⁰

Discussion

Herein we have described efficient synthetic procedures for the synthesis of a tridentate phosphine ligand and a series of ruthenium complexes. The N-triphos^Ph ligand (1) can be easily prepared in high yield with a minimalistic work-up procedure. This phosphorus based Mannich reaction used to synthesize these types of ligands is quite general and can be used for other ligand derivatives with differing R-groups on the P-atoms.^10-12,15-18 Additionally, this synthetic methodol...

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Methanol			Obtained from in-house solvent purification system: Innovative Technology, inc "pure solv" drying tower. Stored in ampules over activated molecular sieves under nitrogen.
Toluene
Diethyl Ether
Tetrahydrofuran (THF)
Acetonitrile
d6-Acetone	VWR	VWRC87152.0011	Store in fridge
Triethylamine	Sigma-Aldrich	TO886-1L	Distilled and stored over activated molecular sieves under N2
2 M Ammonia solution in methanol	Sigma-Aldrich	341428-100ML	Solution comes in a "Sure-Seal" bottle
NH4PF6	Sigma-Aldrich	216593-5G	Store in desiccator
Levulinic Acid	Acros Organics	125142500	Solid but melts close to room temperature
3 Å Molecular sieves	Alfa Aesar	LO5359	Activate by heating over night under vacuum
Schlenk flasks	GPE	Custom design
Dual-manifold Schlenk line	GPE	Custom design	Dual-manifold of i) N2 that has been passed through a silica drying column and ii) vacuum.
Rotary vacuum pump	Edwards	RV3 A652-01-903
100 ml Autoclave Engineer's high pressure reactor	Autoclave Engineer	Custon design
Vortex Stirrer	VWR	444-1378