Synthesis and Catalytic Properties of a Very Latent Selenium-Chelated Ruthenium Benzylidene Olefin Metathesis Catalyst

Herein, we describe a study of the synthesis, characterization, and catalytic properties of a cis-dichlorido seleno-chelated Hoveyda–Grubbs type complex (Ru8). Such a complex has been obtained through a straightforward and high-yielding synthetic protocol in three steps from the commercially available 2-bromobenzaldehyde in good overall yield (54%). The catalytic profile, especially the latency of this complex, has been probed through selected olefin metathesis reactions such as ring-closing metathesis (RCM), self-cross-metathesis (self-CM) and ring-opening metathesis polymerization (ROMP). In addition to its high latency, the selenium Hoveyda-type complex Ru8 exhibits a switchable behavior upon thermal activation. Of interest, while the corresponding sulfur-chelated Hoveyda type catalyst is reported to be only activated by heat, the selenium analogue was found to be active upon both heat and light irradiation.

using a Shimadzu model RID-20A. The system was calibrated using poly(styrene) standards (PSS GmbH) in the range of molecular weights 2.09-323 kDa. Molecular weight analysis by Size Exclusion Chromatography (SEC) has been performed from samples dissolved in THF (1 mg/mL) followed by filtration on Pall PTFE membrane filters (0.2 μm); 20 uL injections were applied. The polymers were analyzed after the removal of the catalyst and unreacted monomers by precipitation of the polymers and filtration with methanol.

Synthesis of the Ligand
Scheme S1. Synthesis of bromostyrene derivative 2 via Wittig olefination.
Ethyltriphenylphosphonium bromide (8.7 g, 23.1 mmol, 2.3 equiv.) and potassium tertbutoxide (2.7 g, 23.1 mmol, 2.3 equiv.) were placed in an oven-dried flask. 20 mL of anhydrous THF was added. Reaction mixture was stirred at room temperature for 30 minutes. Then the mixture was cooled down to -78 °C and appropriate aldehyde 1 (1.9 g, 10.1 mmol, 1 equiv.) was added dropwise. Stirring was continued over 2 h at rt. The reaction mixture was quenched with saturated aqueous solution of NH4Cl (50 mL) and the THF was removed under reduced pressure. DCM (50 mL) was added and the layers were separated. Aqueous phase was extracted with DCM (2 x 50 mL). Organic layer was dried over anhydrous MgSO4 and afterwards, the solid was filtered off and the organic solution was concentrated by the evaporation of DCM. Crude product was purified using quick column chromatography (stationary phase: SiO2, eluent: DCM) in order to remove triphenylphosphine oxide from the alkene. The product was obtained as a yellow oil (1.81 g, 91%) and can be used without further purification.
In an glovebox filled with argon, a 25 mL round-bottom flask was charged with Mg (finely ground, 26 mg, 1.1 mmol, 1.1 equiv.), lithium chloride (4.8 mg, 0.1 mmol, 0.1 equiv.) and THF (3 mL). To the resulting suspension, the solution of bromostyrene derivative 2 (200 mg, 1.0 mmol, 1.0 equiv.) in THF (2 mL) was added dropwise. The reaction was stirred at room temperature until the complete consumption of magnesium (leading to a clear colorless to pale yellow solution). The Grignard reagent was thus formed and gray Se (80 mg, 1.0 mmol, 1.0 equiv.) was added in one portion while stirring vigorously. The dark suspension of selenium in the reaction mixture turned rapidly (after 5 minutes) into a homogeneous clear orange solution indicating the full conversion of selenium. The flask was taken outside of the glovebox and 2-iodopropane (509 mg, 3 mmol, 3 equiv.) was added to the reaction mixture. After the addition of alkylating agent, a precipitate appears instantly leading to a grey to yellow turbid suspension. The reaction mixture was stirred at room temperature overnight and afterwards water was added (5 mL). The product was extracted with DCM (3 x 10 mL). The organic phases were combined, washed with brine and dried over anhydrous Na2SO4. The volatiles were removed under reduced pressure and the yellow oil was dried overnight under high vacuum (1•10 -3 mbar). The product 3 was obtained as yellow oil (177.6 mg, 74%, E/Z = 1.7:1) and can be used without further purification.

X-Ray Data Collection and Structure Refinement
Good quality single-crystals of Ru8 was selected for the X-ray diffraction experiments at T = 100(2) K. Diffraction data were collected on the Agilent Technologies SuperNova Dual Source diffractometer with MoKα (λ = 0.71073) radiation using CrysAlis RED software. 1 The analytical numerical absorption correction using a multifaceted crystal model based on expressions derived by R.C. Clark & J.S. Reid, 2 implemented in SCALE3 ABSPACK scaling algorithm, were applied. 14 The structural determination procedure was carried out using the SHELX package. 3 The structures were solved with direct methods and then successive least-square refinement was carried out based on the full-matrix least-squares method on F 2 using the SHELXL program. 3 All H-atoms were positioned geometrically with C-H equal to 0.93, 0.96, 0.97 and 0.98 Å for the aromatic, methyl, methylene and methine H-atoms, respectively. The H-atoms were constrained to ride on their parent atoms with Uiso(H) = xUeq(C), where x = 1.2 for the aromatic, methylene and methine Hatoms, and 1.5 for the methyl H-atoms, respectively. Additionally, several distinct peaks on the difference Fourier map of Ru8 were indicating the presence of a disordered solvent molecule/s. However, all of the attempts to propose reasonable model of disorder have failed. Therefore, the solvent contribution was removed by applying the appropriate MASK procedure in the Olex2 program. 4 Calculated total solvent accessible volume / cell was 919.  1.35/-1.30 S10 Figure S1. ORTEP diagram of Ru8 with 50% probability ellipsoids; hydrogen atoms were omitted for clarity.

Activation of Ru8 and Catalytic Activity
Demonstration of Ru8 Latency Scheme S4. RCM reaction of 4 as a method for Ru catalysts activity assessment.
Procedure: In a glovebox filled with argon, diene 4 (48.5 mg, 50 µL, 0.2 mmol, 1 equiv.) was added to a solution of Ru8 (1.38 mg, 0.002 mmol, 1 mol%) in C6D6 (0.4 mL) in a screw cap NMR tube. The NMR tube was taken outside of the glovebox and the reaction mixture was stirred at 20 °C for the required time. Data was recorded using 32 scans with a D1 delay time minimum of 1 s between each pulse. Progress of the reaction was monitored through the disappearance of the methylene signals of 4 (2.63 ppm) and the growth of the methylene proton signal of the product 5 (3.01 ppm). After the time of 1 month, the conversion of the diene 4 to the corresponding cycloalkene derivative 5 was not observable. In a glovebox filled with argon, a screw cap NMR tube was charged with Ru8 (5 mg, 0.0072 mmol) in CD2Cl2 (0.5 mL). The NMR tube was taken outside of the glovebox and placed in a UV-reactor. Data was recorded using 32 scans with a D1 delay time minimum of 1 s between each pulse. Progress of the reaction was monitored through the disappearance of the benzylidene signal of cis-Cl2 Ru8 (17.46 ppm) and the growth of the benzylidene signal of trans-Cl2 Ru8 (17.72 ppm).  In a glovebox filled with argon, a screw cap NMR tube was charged with Ru8 (5 mg, 0.0072 mmol) in C6D6 (0.5 mL). The NMR tube was taken outside of the glovebox and placed in a UV-reactor. Data was recorded using 32 scans with a D1 delay time minimum of 1 s between each pulse. Progress of the reaction was monitored through the disappearance of the benzylidene signal of cis-Cl2 Ru8 (17.46 ppm) and the growth of the benzylidene signal of trans-Cl2 Ru8 (17.72 ppm).

Activity of Ru8 in RCM Reactions with Thermal Activation in C6D6
Scheme S7. RCM reaction of 4 promoted by Ru8 complex at increased temperature.
Procedure: In a glovebox filled with argon, diene 4 (48.5 mg, 50 µL, 0.2 mmol, 1 equiv.) was added to a solution of Ru8 (1.38 mg, 0.002 mmol, 0.1 mol%) in C6D6 (0.4 mL) in a screw cap NMR tube. The NMR tube was taken outside of the glovebox and the reaction mixture was heated in an oil bath at 80 °C for the required time. Data was recorded using 32 scans with a D1 delay time minimum of 5 s between each pulse. Progress of the reaction was monitored through the disappearance of the methylene signals of 4 (2.63 ppm) and the growth of the methylene proton signal of the product 5 (3.01 ppm). Figure S7. Progress of the RCM reaction of 4 in benzene-d6 at 80 °C monitored by 1 H NMR. S19 Figure S8. Progress of the RCM reaction of 4 in benzene-d6 at 80 °C monitored by 1 H NMR.

Activity of Ru8 in RCM Reactions with Thermal Activation in C6D5CD3
Scheme S8. RCM reaction of 4 promoted by Ru8 complex at increased temperature.
Procedure: In a glovebox filled with argon, diene 4 (48.5 mg, 50 µL, 0.2 mmol, 1 equiv.) was added to a solution of Ru8 (1.38 mg, 0.002 mmol, 0.1 mol%) in deuterated toluene (0.4 mL) in a screw cap NMR tube. The NMR tube was taken outside of the glovebox and the reaction mixture was heated in an oil bath at 80 °C for the required time. Data was recorded using 32 scans with a D1 delay time minimum of 5 s between each pulse. Progress of the reaction was monitored through the disappearance of the methylene signals of 4 (2.63 ppm) and the growth of the methylene proton signal of the product 5 (3.01 ppm). Procedure: In a glovebox filled with argon, diene 4 (48.5 mg, 50 µL, 0.2 mmol, 1 equiv.) was added to a solution of Ru8 (1.38 mg, 0.002 mmol, 0.1 mol%) in deuterated toluene (0.4 mL) in a screw cap NMR tube. The NMR tube was taken outside of the glovebox and the reaction mixture was heated in an oil bath at 110 °C for the required time. Data was recorded using 32 scans with a D1 delay time minimum of 5 s between each pulse. Progress of the reaction was monitored through the disappearance of the methylene signals of 4 (2.63 ppm) and the growth of the methylene proton signal of the product 5 (3.01 ppm).    Procedure: In a glovebox filled with argon, diene 4 (48.5 mg, 50 µL, 0.2 mmol, 1 equiv.) was added to a solution of Ru8 (1.38 mg, 0.002 mmol, 0.1 mol%) in CD2Cl2 (0.4 mL) in a screw cap NMR tube. The NMR tube was taken outside of the glovebox and placed in the UV photoreactor (λ = 365 nm) for a required time. Data was recorded using 32 scans with a D1 delay time minimum of 1 s between each pulse. Progress of the reaction was monitored through the disappearance of the methylene signals of 4 (2.63 ppm) and the growth of the methylene proton signal of the product 5 (3.01 ppm).

Activity of Ru8 in RCM Reactions with Photochemical Activation in Benzene
Scheme S11. RCM reaction of 4 promoted by Ru8 complex under irradiation.
Procedure: In a glovebox filled with argon, diene 4 (48.5 mg, 50 µL, 0.2 mmol, 1 equiv.) was added to a solution of Ru8 (1.38 mg, 0.002 mmol, 0.1 mol%) in C6D6 (0.4 mL) in a screw cap NMR tube. The NMR tube was taken outside of the glovebox and placed in the UV photoreactor (λ = 365 nm) for a required time. Data was recorded using 32 scans with a D1 delay time minimum of 1 s between each pulse. Progress of the reaction was monitored through the disappearance of the methylene signals of 4 (2.63 ppm) and the growth of the methylene proton signal of the product 5 (3.01 ppm).   15 mL vial equipped with a screw cap was charged with substrate COE (323 mg, 385 µL, 2.93 mmol, 1 equiv.). Unless the reaction was carried out in neat, an appropriate solvent (6 mL) was added (DCM or toluene). To the resulting solution mesitylene (353 mg, 407 µL, 2.93 mmol, 1 equiv.) was added as internal standard followed by the addition of Ru8 catalyst stock solution in DCM (1 M, 0.3 mL, 0.303 mg, 0.44 µmol, 150 ppm, 0.0150 mol%). For the reactions carried out in neat conditions, the solvent (DCM) was removed under the reduced pressure before photochemical activation. The vial was then placed in the UV-reactor (365 nm) or in heated oil bath (80 °C) and was left for a required time affording a highly viscous solution. NMR of this crude solution was recorded and highlighted the presence of the polymer. The resulting polymer was precipitated out with acetone and methanol then filtered off. In the case of reaction in neat, the solid was washed with hexane and DCM and filtered. The filtrate was analyzed by 1 H NMR to assess the conversion of the reaction.
15 mL vial equipped with a screw cap was charged with DCPD (500 mg, 3.67 mmol, 1 equiv.) and mesitylene (441 mg, 508 µL, 3.67 mmol, 1 equiv.) as internal standard. To the resulting mixture was added Ru8 catalyst stock solution (1 M, 0.38 mL, 0.378 mg, 0.55 µmol, 150 ppm, 0.0150 mol%). The solvent (DCM) was removed under the reduced pressure before photochemical activation. The vial was then placed in the UV-reactor (365 nm) and was left for a required time affording a transparent solid polymer (hard and odorless). The table containing the results of conducted ROMP reactions is presented below.

Polymerization of Norbornene
Scheme S14. ROMP polymerization of norbornene promoted by Ru8 catalyst under UV irradiation.
For the reactions carried out in neat conditions, the solvent (DCM) was removed under the reduced pressure before photochemical activation. The vial was then placed in the UVreactor (365 nm) or in heated oil bath (80 °C) and was left for a required time affording a highly viscous solution. NMR of this crude solution was recorded. The resulting polymer was precipitated out with acetone and methanol then filtered off. In the case of reaction in neat, the solid was washed with hexane and DCM and filtered. The filtrate was analyzed by 1 H NMR to assess the conversion of the reaction.
In case of reaction with 10 ppm of Ru8, the following conditions has been used: To a 15 mL screw capped vial containing 6 (1026 mg, 10.9 mmol, 1 equiv.), mesitylene (1310 mg, 1510 µL, 10.9 mmol, 1 equiv.) was added as internal standard followed by the addition of Ru8 catalyst stock solution in DCM (1 mg/mL, 0.075 mL, 0.075 mg, 0.11 µmol, 10 ppm, 0.0010 mol%).  Figure S24. GPC traces of the polynorbornene obtained from the reaction of 6 (1.0 equiv.) with 10 ppm of Ru8 in neat with light activation.  For the reactions carried out in neat conditions, the solvent (DCM) was removed under the reduced pressure before photochemical activation. The vial was then placed in the UVreactor (365 nm) or in heated oil bath (80 °C) and was left for a required time affording a highly viscous solution. NMR of this crude solution was recorded and highlighted the presence of the polymer polyCOD, which was subsequently precipitated out with acetone and then filtered off. Despite the flexibility of the obtained material, it can be broken easily on elongation. The filtrate was analyzed by NMR spectroscopy to determine the conversion of the substrate. The table containing the results of conducted ROMP reactions is presented below. Methyl oleate (MO) (341 μL, 1 mmol) was introduced into a 1.5 mL screw-capped vial. The air in the flask was replaced by argon. The catalyst Ru8 (0.69 mg, 0.001 equiv., 1 μmol, 0.1 mol% or 0.35 mg, 0.5 µmol, 0.05 mol%) was added as DCM solution (1 mg/mL). The solvent (DCM) was evaporated from the vessel under reduced pressure followed by refilling the vial with argon atmosphere before placing the vial in a UVreactor. Then, the reaction mixture was irradiated for 14 h. After this time, a solution of SnatchCat was added and the reaction mixture was diluted in toluene. The resulting solution was injected to the GC-MS.