Latent ruthenium–indenylidene catalysts bearing a N-heterocyclic carbene and a bidentate picolinate ligand

A silver-free methodology was developed for the synthesis of unprecedented N-heterocyclic carbene ruthenium indenylidene complexes bearing a bidentate picolinate ligand. The highly stable (SIPr)(picolinate)RuCl(indenylidene) complex 4a (SIPr = 1,3-bis(2-6-diisopropylphenyl)imidazolidin-2-ylidene) demonstrated excellent latent behaviour in ring closing metathesis (RCM) reaction and could be activated in the presence of a Brønsted acid. The versatility of the catalyst 4a was subsequently demonstrated in RCM, cross-metathesis (CM) and enyne metathesis reactions.


General
All the reactions were carried out under inert atmosphere (argon).
Dichloromethane was distilled over calcium hydride prior to use.
Tetrahydrofuran was distilled over sodium/benzophenone prior to use. All commercial chemicals were used as received unless otherwise noted. 1 H (400 MHz) and 13 C (100 MHz) NMR spectra were recorded on a Bruker ARX400 spectrometer with complete proton decoupling for 13 C. 1 H and 13 C chemical shifts are reported in parts per million with the solvent resonance as the internal standard (CDCl 3 , 1 H:  7.26 ppm, 13 C:  77.16 ppm; CD 2 Cl 2 , 1 H:  5.31, 13 C:  53.8 ppm). Coupling constants are reported in Hertz (Hz).
In a flame-dried Schlenk tube equipped with a stirring bar, complex 1 (500.0 mg, 0.53 mmol), 2-picolinic acid (71.4 mg, 0.58 mmol) and copper(I) chloride (97%, 80.7 mg, 0.79 mmol) were added. The Schlenk tube was then submitted to 3 argon-vacuum cycles after which 12 mL of CH 2 Cl 2 were added. The reaction mixture was stirred for 2 h at 35 °C after what it was evaporated to dryness. The solid was dissolved in acetone and filtrated on a short plug of celite to remove the copper salts. The filtrate was concentrated under reduced pressure and the crude material was then purified by flash chromatography on silica gel (pentane/acetone, 9:1 to 8:2), affording compound 2 as a red powder in 62% yield (272.0 mg, 0.36 mmol).
The Schlenk tube was then submitted to 3 argonvacuum cycles after which 2 mL of CH 2 Cl 2 were added. The reaction mixture was stirred for 3 hours after which it was evaporated to dryness.
The crude mixture was then purified by flash chromatography on silica gel (pentane/acetone, 8/2), affording compound 4a as a red powder in 62% yield (62 mg, 0.073 mmol). Crystals suitable for X-ray diffraction were obtained by slow diffusion of pentane in a solution of 4a in CH 2 Cl 2 (ca. 5 mg in 0.5 mL CH 2 Cl 2 , 2 mL pentane).

Determination of the acid quantity influence in the RCM of DEDAM with 4a
In a flame-dried NMR tube under Argon, DEDAM (19 L, 0.08 mmol), mesitylene (11 L, 0.08 mmol) and CD 2 Cl 2 (800 L) were added. A solution of catalyst 4a in CD 2 Cl 2 was prepared in a separate flask under Argon and the catalyst was injected in the NMR tube (0.0008 mmol). After 30 minutes, an NMR spectrum was recorded after what the tube was ejected and TFA (between 1 and 12 L) was added. NMR spectra were then taken at regular intervals and the reaction conversion was determined with the integral ratio of the reaction product with mesitylene.

Catalyst comparison in the RCM of DEDAM with TFA
In a flame-dried NMR tube under Argon, DEDAM (19 L, 0.08 mmol), mesitylene (11 L, 0.08 mmol) and CD 2 Cl 2 (800 L) were added. A solution of catalyst in CD 2 Cl 2 was prepared in a separate flask under Argon and the catalyst was injected in the NMR tube (0.0008 mmol). After 30 minutes, an NMR spectrum was recorded after what the tube was ejected and TFA (9 L, 0.12 mmol) was added. NMR spectra were then taken at regular intervals and the reaction conversion was determined with the integral ratio of the reaction product with mesitylene.

Acid comparison in the RCM of DEDAM with 4a
In a flame-dried NMR tube under Argon, DEDAM (19 L, 0.08 mmol), mesitylene (11 L, 0.08 mmol) and CD 2 Cl 2 (800 L) were added. A solution of catalyst 4a in CD 2 Cl 2 was prepared in a separate flask under Argon and the catalyst was injected in the NMR tube (0.0008 mmol). After 30 minutes, an NMR spectrum was recorded after what the tube was ejected and the acid (0.12 mmol) was added. NMR spectra were then taken at regular intervals and the reaction conversion was determined with the integral ratio of the reaction product with mesitylene.