N-hydrazine cyclic(amino)(alkyl)carbene ruthenium complexes: synthesis and reactivity in olefin metathesis

Abstract

The synthesis of a ruthenium complex containing an N-hydrazine cyclic(amino)(alkyl)carbene (CAAC) ligand is reported. This robust and air-stable complex demonstrates good to excellent catalytic performances under an air atmosphere in various ring-closing metathesis (RCM), ring-closing enyne metathesis (RCEYM), ring-opening cross-metathesis (ROCM), self-metathesis (SM), cross-metathesis (CM) and ethenolysis reactions.

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Olefin metathesis is one of the most efficient catalytic tools for the formation of C=C bonds, which are ubiquitous in many relevant molecules that are widely used in materials science, crop protection, pharmaceuticals, cosmetics and perfumery.¹ Since their first synthesis in 2007,² well-defined ruthenium complexes Ru1 with cyclic (alkyl)(amino)carbene (CAAC)³ ligands (Fig. 1a) have brought seminal breakthroughs in the field of olefin metathesis,⁴ notably with the highest productivity in ethenolysis (TON up to 2 600 000)⁵ and in ring-closing metathesis (68 000).⁶ Thanks to their high modularity and straightforward synthesis, CAACs are most often tuned at the α-quaternary carbon (alpha to the carbene carbon)⁵ or by modification of the heterocyclic backbone (Ru2–4)^7–9 (Fig. 1a). Comparatively, structural variation at the nitrogen has seldom been considered and has so far been restricted to aryl and alkyl substituents.¹⁰ Herein, we report the synthesis of CAAC iminium salt precursors containing an N-hydrazine fragment, namely ^HydrazCAAC·BF₄ (Fig. 1b). This new ligand framework yields a robust and air-stable olefin metathesis complex Ru5 which has been isolated and fully characterised by X-ray diffraction. Interestingly, this complex displays high thermal stability at 80 °C with good to excellent catalytic performance in olefin metathesis reactions performed in air using ACS grade solvents.

Fig. 1 State of the art of CAAC–Ru complexes for olefin metathesis (a) and the development of a new CAAC–Ru complex featuring an N-hydrazine unit (b, this work).

We initiated our study by preparing CAAC iminium salts ^HydrazCAAC-1a,b·BF₄ containing an N-hydrazine substituent (Scheme 1a). Starting from pre-alkylated aldehydes 1a,b,¹¹ condensation with phenylmethylhydrazine 2 led to the desired imines 3a,b. Subsequent hydroiminiumation^3b and anionic metathesis afforded the corresponding iminium salts ^HydrazCAAC-1a,b·BF₄ which were isolated in 50% and 46% yields, respectively, close to those of previously reported CAACs.^4,11 Using these ligands, we investigated the synthesis of Hoveyda type Ru-complexes Ru5a,b by deprotonation of these salts with potassium hexamethyldisilazide (KHMDS) and in situ reaction with first generation Hoveyda–Grubbs (HG1) catalyst precursor (Scheme 1b). While no complexation could be observed with ^HydrazCAAC-1a leading to Ru5a, we were delighted to isolate Ru5b from ^HydrazCAAC-1b in 41% yield.

Scheme 1 Synthesis of N-hydrazine CAAC precursors (a) and related ruthenium complexes (b). ^a Isolated yield.

Gratifyingly a suitable crystal of Ru5b allowed us to confirm the structure of this complex by X-ray diffraction which allowed us to gain valuable structural information (Fig. 2). Notably, it revealed that Ru5b belongs to the rare class of “inverted” CAAC complexes,^4,13 which are characterized by an α-quaternary centre positioned above the isopropoxybenzylidene moiety. The small %buried volume (%V_bur) of 34.9% observed for Ru5b confirmed the low steric hindrance of this ligand framework. We also noted that the N,N-phenyl substituent and the tetrahydronaphtalene moiety adopt a cis-relationship, leading to lower space occupancy in the bottom quadrants (as highlighted in the space filling views).

Fig. 2 Solid-state structure and steric map/buried volume of complex Ru5b from single-crystal X-ray diffraction. Displacement ellipsoids are drawn at 30% probability. Hydrogen atoms have been omitted for clarity. The calculated buried volume (%V_bur) and steric maps (radii 3.5 and 5 Å) (see ref. 12). ^a Isopropoxybenzylidene ligand and Cl atoms have been omitted for clarity.

Next, we evaluated the thermal stability of Ru5b in toluene-d₈ solution at 80 °C in air (Fig. 3). Interestingly, in this case up to 91% of the remaining complex was observed after 5 hours with only 30% decomposition occurring after 2 days. Similar behaviour was also observed with commercially available Ru1a,^2b which decomposed more slowly, with only 1% lost after 5 h (see Fig. 3).

Fig. 3 Thermal stability of Ru5b and commercially available Ru1a in toluene-d₈ at 80 °C under an air atmosphere. 1,3,5-Trimethoxybenzene was used as the internal standard (see the SI for details).

Encouraged by the high stability of Ru5b in solution, we next investigated its catalytic performances in olefin metathesis performed in air using ACS grade solvents. First, we evaluated ring-closing metathesis (RCM) using 0.1 mol% catalyst loading at 50 °C (Scheme 2a). Good to excellent yields (81–99%) were obtained for mono-, di- or trisubstituted cyclopentenes 2a, 2b and 2d. However, no or poor conversion was observed for the more sterically hindered tetrasubstituted cyclopentenes 2c and 2e, despite higher catalyst loading (1 mol%) and elevated temperature (80 °C). It should be noted that a slightly lower 91% yield was observed with Ru1a.

Scheme 2 Scope of RCM (a) and RCEYM (b) catalysed by Ru5b. ^a Conversions were determined by ¹H NMR spectroscopy. ^b Yields were determined by ¹H NMR spectroscopy using 1,3,5-trimethoxybenzene as the internal standard.

Seven-membered ring products 2f and 2g were obtained with excellent yields (99% and 87% yield, respectively) while a moderate 40% yield was obtained for the cyclic silane 2h. Note that the Ru5b remains active at lower catalyst loading with up to 79% conversion of 2g observed with 0.01 mol% catalyst loading. The ring-closing enyne metathesis (RCEYM) reactions were realized with a higher catalyst loading (2%) at 80 °C (Scheme 2b). While full conversion and good yield (84%) were obtained for product 4a, a lower reactivity was observed for compound 4b (20%).

We next considered ring-opening cross-metathesis (ROCM) reactions involving both endo and exo norbornene derivatives with styrene as a cross-olefin partner. As depicted in Scheme 3, ^exo5a and ^exo5b displayed excellent reactivity at 0.1 mol% catalyst loading, affording corresponding trans-cyclopentanes 6a and 6b with a high yield (95–96% respectively) and E/Z ratio (96 : 4 to 97 : 3). Regarding ^endo7, a catalyst loading of 1 mol% was necessary to complete the reaction, leading to expected cis-cyclopentanes 8 with 78% yield and 91 : 9 E/Z ratio.

Scheme 3 Scope of ROCM catalysed by Ru5b. ^a Conversions were determined by ¹H NMR spectroscopy. ^b Yields were determined by ¹H NMR spectroscopy using 1,3,5-trimethoxybenzene as the internal standard. ^c The E/Z ratio was monitored by GC/MS analysis.

We also explored self-metathesis reactions using different terminal olefins and a catalyst loading of 0.5 mol% (Scheme 4a). 1-Dodecene 9a and allylbenzene 9b gave the corresponding internal alkenes 10a and 10b in good yield (73 and 78% respectively), while substrates 9c and 9d containing an acetate or an ester moiety afforded the desired homo-metathesis products 10c and 10d with good to excellent yield (74% and 84% respectively). In comparison, cross-metathesis (CM) performed using various functionalized cross-olefin partners required a higher catalyst loading (2 mol%, Scheme 4b). In this case cross-coupling between 4-penten-1-ol 11a and 1-dodecene 12a at 50 °C led to 13a in 45% yield and a 67 : 33 E/Z ratio. A lower 31% isolated yield was observed for product 13b, despite a higher temperature (80 °C) and a prolongated time (20 h). The reaction between allyl acetate 11c and allyl-benzene 12c yielded the corresponding metathesis product 13c in 50% and a 86 : 14 E/Z ratio. Replacing 11c with its dimer counterpart, i.e. cis-1,4-diacetoxy-2-butene 11d allowed significantly increasing the isolated yield (84%, Scheme 3c) under the same conditions. To complete our catalytic evaluation, we also investigated the performance of Ru5b in the ethenolysis of methyl oleate 14 (Scheme 3d).

Scheme 4 Scope of SM, CM and ethenolysis reactions catalysed by Ru5b. ^a Conversions were determined by ¹H NMR spectroscopy. ^b Yields were determined by ¹H NMR spectroscopy using 1,3,5-trimethoxybenzene as the internal standard. ^c Isolated yield. ^d The E/Z ratio was determined by GC analysis. ^e The E/Z ratio was determined by ¹³C NMR analysis. ^f The E/Z ratio was determined by ¹H NMR analysis. ^g Conversion and yield determined by GC analysis.

With a catalyst loading of 0.3 mol% and 10 bar of ethylene pressure (99.95% purity), the expected methyl 9-decenoate 15 was isolated in respectable 63% yield. However, lowering the catalyst loading to 0.1 mol% led to poor conversion (<5%, see the SI for details). Before this, we investigated the stability of Ru5b in the presence of ethylene (10 bar) at 40 °C^13b in non-degassed and non-distilled CD₂Cl₂. We observed a rapid decomposition as only 28% of the remaining precatalyst was observed after 30 min (17% after 6 hours, see the SI for details). Further developments are thus required to improve the efficiency of N-hydrazine CAAC Ru complexes for ethenolysis.

In summary, we have reported the synthesis of a new class of CAAC ligands incorporating an N-hydrazine motif which has so far remained unexplored. We confirm that these ligands provide a robust architecture for ruthenium olefin metathesis complexes leading to thermal stability up to 80 °C in air. While its performance in cross-metathesis is still modest, the complex excelled in a broad array of transformations including RCM, RCEYM, ROCM, and SM reactions delivering high efficiency at catalyst loadings as low as 0.1 mol%. Advantageously, all reactions can be performed without the need for distilled and degassed solvents. Further developments are underway to explore the scope of its applications, notably in reactions performed under sustainable and industrially relevant experimental conditions.

R. J., A. D. and M. M. conceptualized and supervised this work. C. C. conducted all the experiments. T. R. accomplished the X-Ray diffraction analysis. The manuscript was written by R. J. and M. M. and was reviewed by all the authors.

We are grateful to the CNRS, the ENSC de Rennes and San Diego State University. This work was supported by Umicore AG & Co (grant to C. C.).

Conflicts of interest

There are no conflicts to declare.

Data availability

All experimental and crystallographic data associated with this work are available in the SI.

Experimental procedures, NMR spectra, and GC analysis. See DOI: https://doi.org/10.1039/d5cc03776j.

CCDC 2440954 contains the supplementary crystallographic data for this paper.¹⁴

Notes and references

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