Consequences of the electronic tuning of latent ruthenium-based olefin metathesis catalysts on their reactivity

Two ruthenium olefin metathesis initiators featuring electronically modified quinoline-based chelating carbene ligands are introduced. Their reactivity in RCM and ROMP reactions was tested and the results were compared to those obtained with the parent unsubstituted compound. The studied complexes are very stable at high temperatures up to 140 °C. The placement of an electron-withdrawing functionality translates into an enhanced activity in RCM. While electronically modified precatalysts, which exist predominantly in the trans-dichloro configuration, gave mostly the RCM and a minor amount of the cycloisomerization product, the unmodified congener, which preferentially exists as its cis-dichloro isomer, shows a switched reactivity. The position of the equilibrium between the cis- and the trans-dichloro species was found to be the crucial factor governing the reactivity of the complexes.


Scheme 1. Alternative synthesis of 13.
According to a literature procedure 1 2-bromoaniline (58.2 mmol, 10 g) was dissolved in 30 mL of 6 N HCl and stirred under reflux. Crotonaldehyde (64 mmol, 5.3 mL) was added dropwise. The reaction was refluxed overnight. It was then cooled down. 40 mL of diethyl ether were added followed by addition of anhydrous zinc chloride (58.2 mmol, 7.9 g). The reaction mixture was stirred for 15 minutes at room temperature, and further 15 minutes in 0 °C. The formed solid was filtered and washed with 2-propanol until the filtrate became colorless. Then it was washed with 40 mL of diethyl ether and dried. The solid was suspended in 30 mL of water and 10 mL of ammonium hydroxide were added. The mixture was vigorously shaken and extracted with diethyl ether. Combined organic phases were dried over magnesium sulfate and evaporated. The product was purified by CC to give II, as pale yellow solid with 56% yield (32.5 mmol, 7.2g). 1  According to a literature procedure 2 selenium(IV) dioxide (41.5 mmol, 4.6 g) was dissolved in dioxane in a Schlenk tube under argon. The solution was heated to 80 °C. Then II (41.5 mmol, 9.2 g) was added. The reaction mixture was heated overnight, then cooled down to room temperature and filtered through neutral alumina. The solution was evaporated and the residue was washed with cold acetone to yield III, as a pale yelow solid with 85% yield (35.4 mmol, 8 Tetrakis(triphenylphosphine)palladium (1.77 mmol, 2 g), potassium vinyltrifluoroborate (44.2 mmol, 5.9 mg), tripotassium phosphate (106 mmol, 22.5 g) and compound III (35.4 mmol, 8.3 g) were placed in a Schlenk tube under argon. Anhydrous THF (250 mL) was added and the solution was refluxed overnight under argon atmosphere. After this time the reaction mixture was cooled, water (150 mL) was added and the aqueous layer was extracted with dichloromethane (3 × 100 mL). The combined organic layers were dried and concentrated in vacuo. The crude product was purified by s5 flash chromatography using eluents: c-hexane/ethyl acetate 10:1 to 1:1 v/v to provide the product. Multiple column chromatographies and crystallizations resulted in 13 (14.3 mmol, 2.6 g) with 40% yield, spectroscopically pure as described part 2.2.

Synthesis of ruthenium complexes
Precursor complex 1 (0.5 mmol, 475 mg) and the respective styrene derivative (0.55 mmol) were put in a Schlenk tube under argon. Reagents were dissolved in anhydrous toluene (25 mL) and the reaction was heated in 80 °C for about an hour. Then the solvent was evaporated and the mixture was purified by a flash chromatography using eluents: c-hexane/ethyl acetate 10 : 1 to 1 : 1 v/v. The solvent was evaporated. It was then re-dissolved in DCM and cold n-heptane was added to produce crystals of the product. Crystals suitable for X-ray analysis were grown form the DCM / n-heptane mixture.
14, dark brown crystals (0.37 mmol, 242 mg, 75%   Sample preparation for STA measurements with DCPD (23) DCPD (23), which is solid at room temperature, was molten in a 35-40 °C water bath before use. Initiator 5a (4.92 mg), 14 (4.88 mg) and 15 (4.88 mg) were dissolved in 600 µL dichloromethane (c [Ru] =12.6•10 −3 M). 60 µL of this stock solution (0.76•10 −3 mmol) were transferred into a 2 mL glass vial and 1.0 mL of liquid DCPD (7.4 mmol) was added with a syringe, so that the batch was well mixed. The total content of solvent in the mixture is 7.4 w.-% (d DCM = 1.33 g•mL −1 , d DCPD = 0.98 g•mL −1 ). The vial was immediately put into liquid nitrogen to shock-freeze the mixture. For transportation the vial was stored in a Styropfoam container. About 8-12 mg of the mixture was transferred into a cooled DSC pan, which was then subjected to the STA run. The analysis was run with a constant He gas stream of 50 mL•min −1 at a heat rate of 3 K•min −1 , starting at 20 °C.

2.8.2.
Sample preparation for STA measurements with diethylester-norbornene 22 A stock solution of 5a (4.92 mg), 14 (4.88 mg) and 15 (4.88 mg) was prepared (c [Ru] = 13.9•10 −3 M). 60 µL of this stock solution (0.83•10 −3 mmol) were transferred into a 2 mL glass vial and 100 mL of liquid 22 (d mon2 = 1.0 g•mL −1 , 0.42 mmol) were added and well mixed. The solvent was removed by a N 2 -stream and then immediately shock frozen by liquid nitrogen to avoid any premature activation. For transportation the vial was stored in a Styropfoam container. About 8-12 mg of the mixture was transferred into a cooled DSC pan, which was then subjected to the STA run. The analysis was run with a constant He gas stream of 50 mL•min −1 at a heat rate of 3 K•min −1 , starting at 20 °C.

2.8.3.
Polymerization of dimethylester-norbornene 21 in solution In a Schlenk flask, 5a, 14 and 15 (1.27 µmol, 1.0 equiv) were dissolved in toluene (3.8 mL, c mon =0.1 M). Subsequently, the mixture was heated to 80 °C then 21 (100.0 mg, 0.38 mmol, 300 eqiuv) was added, dissolved in 1 mL toluene. The reaction was followed by TLC using c-hexane:ethyl acetate, 3:1 (v:v) and KMnO 4 solution for staining. Furthermore, the progress of the reaction was monitored by sampling 200 µL of the reaction mixture and recording 1 H NMR spectra of the quenched sample once to twice a day. After no further conversion was observed due to very high viscosity, an excess of ethyl vinylether was added (200 µL) and stirred for 15 more minutes. Subsequently, the polymer was precipitated in cold, stirred methanol. The white solid was sampled and dried in vacuum. Characteristic polymer properties were examined by gel permeation chromatography (GPC) in THF against polystyrene standard. 2.9. Trans-cis Isomerization 2.9.1. NMR studies In a 0.5-2 mL tube, 5a, 14 and 15 (45.4 µmol, 1.0 equiv) were dissolved in degassed CDCl 3 (0.7 mL). Subsequently, the mixture was heated to 140 °C in microwave. The isomerization was monitored by 1 H NMR spectroscopy (CDCl 3 , 25 °C, 300 MHz) within the carbene region.

Preparation of cis-5a
Isomerization was obtained by exposing 50 mg of trans-5a complex, dissolved in 3 mL CDCl 3 for 30 min in a microwave at 140 °C. The raw product was identified by 1 H NMR spectroscopy (300 MHz) to be the desired cis-isomer. Traces of decomposition material and trans-compound were removed by precipitation with n-pentane and column chromatography on silica gel with CH 2 Cl 2 :MeOH 20:1 (v:v).

X-ray crystallographic details
Diffraction data for both compounds were collected at 90(2) K by the ω-scan technique using 15: BRUKER KAPPA APEXII ULTRA controlled by APEXII 3 software, equipped with MoKα rotating anode Xray source (λ = 0.71073 Å, 50.0 kV, 22.0 mA) or 14: Kuma KM4CCD κ-axis diffractometer or with graphite-monochromated Mo Kα radiation (λ = 0.71073 A, 50.0 kV, 40.0 mA). Both experiments were conducted at 100K, using the Oxford Cryostream cooling device. Crystal was mounted on a nylon loop with a droplet of Paratone-N oil and immediately cooled. Indexing, integration and scaling were performed with original software. 3 The multi-scan absorption correction was applied in the scaling procedure. Structures were solved by direct methods approach using the SHELXS-97 program and refined with the SHELXL-97 using the full-matrix least-squares procedure on F2. 4 Scattering factors incorporated in SHELXL97 were taken from Tables 4.2.6.8 and 6.1.1.4 from the International Crystallographic Tables Vol. C. 5 Details of crystal structure and data refinement are given in Table 1.

Details of computational approach
DFT geometry optimizations were performed at the GGA level with the Gaussian09 package 6 using the BP86 functional of Becke and Perdew. 7 The electronic configuration of the molecular systems was described with the standard splitvalence basis set with a polarization function of Ahlrichs and coworkers for H, C, N, O, and Cl (SVP keyword in Gaussian09), 8 for Ru we used the small-core, quasirelativistic Stuttgart/Dresden effective core potential, with the associated valence basis set (standard SDD keywords in Gaussian09). 9 No symmetry constraint was used and the final geometries were confirmed to be minimum or maximum potential energy structures through frequency calculations. The reported energies have been obtained through single point calculations with the M06 functional of Truhlar. In this case, the electronic configuration of the molecular systems was described by a triple-ζ basis set for main group atoms (TZVP keyword in Gaussian09). 10 Furthermore, diffuse basis sets have been incorporated for Cl and O. 11 Solvent effects including contributions of non-electrostatic terms have been estimated in single point calculations on the gas phase optimized structures, based on the polarizable continuum solvation model PCM using CH 2 Cl 2 and toluene as the solvent. 12