Synthesis of Heavy Fluorous Ruthenium Metathesis Catalysts Using

Article pubs.acs.org/Organometallics

Synthesis of Heavy Fluorous Ruthenium Metathesis Catalysts Using the Stereoselective Addition of Polyfluoroalkyllithium to Sterically Hindered Diimines Jan Hošek,† Markéta Rybácǩ ová,† Jan Č ejka,‡ Josef Cvačka,§ and Jaroslav Kvíčala*,† †

Department of Organic Chemistry, University of Chemistry and Technology, Prague, Technická 5, 166 28 Prague 6, Czech Republic Department of Solid State Chemistry, University of Chemistry and Technology, Prague, Technická 5, 166 28 Prague 6, Czech Republic § Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i., Flemingovo nám. 2, 166 10 Prague 6, Czech Republic ‡

S Supporting Information *

ABSTRACT: The stereoselective addition of 2-(perfluorohexyl)ethyllithium to moderately hindered diimines led to racemic diamines, which were further transformed to light or heavy fluorous analogues of Hoveyda−Grubbs second-generation precatalysts. The complex bearing the NHC ligand modified with four polyfluoroalkyl ponytails represents the first known example of an alkene metathesis precatalyst retaining its heavy fluorous properties in the active catalytic form. The synthesized complexes match the activity and stability of a commercial Hoveyda−Grubbs second-generation precatalyst in model RCM reactions forming tri- and tetrasubstituted double bonds. The fluorophilic catalyst was successfully recycled using heavy fluorous separation techniques.

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first heavy fluorous precatalyst known thus contains a phosphine ligand modified with three (perfluorodecyl)ethyl ponytails (Chart 1).5 A two-phase perfluorocarbon/hydrocarbon solvent system can be used to accelerate the initiation of the precatalyst. However, the active form of this precatalyst is not fluorophilic. We recently reported that substitution of polyfluoroalkyl chains for polyfluoropolyoxaalkyl chains results in a surprisingly higher fluorophilicity in both imidazolium saltbased ionic liquids6 and silver NHC complexes.7 Accordingly, we found that Hoveyda−Grubbs second-generation precatalyst analogues bearing one perfluoroalkyl and two perfluoropolyoxaalkanoate chains have heavy fluorous properties (Chart 1).8 However, the activity and stability of these precatalysts proved to be significantly inferior to those of the parent precatalysts, and we hence concentrated on the fluorous modifications of the NHC imidazolidinylidene ring.

INTRODUCTION Fluorous chemistry is firmly established as an essential part of organic and organometallic chemistry. It uses orthogonal properties of polyfluorinated ponytails for the recycling of homogeneous catalysts, and the separation of products or byproducts of organic reactions, reagent scavengers, etc.1 The recycling of ruthenium metathesis precatalysts remains a controversial issue, with some authors supporting2 and other contesting3 the essential release−return mechanism. However, heavy fluorous ruthenium precatalysts (i.e., the complexes with higher solubility in perfluorinated solvents than in common organic solvents) can benefit from greater hydrophobicity of the catalytic center, a lower ruthenium content in metathesis products, and better separation of catalyst decomposition byproducts and have potential applications in flow systems. Although several authors attempted to synthesize heavy fluorous alkene metathesis catalysts based on a Grubbs or Hoveyda−Grubbs second-generation precatalyst framework, they found that even three polyfluoroalkyl ponytails of average length are not sufficient to provide the desired properties.4 The © XXXX American Chemical Society

Received: April 21, 2015

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DOI: 10.1021/acs.organomet.5b00325 Organometallics XXXX, XXX, XXX−XXX

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Organometallics

hydrogen for the bulky tert-butyl group resulted in the stereoselective formation of the pure threo stereoisomer with no erythro isomer formed (entry 6). High stereoselectivity was also observed when both o-hydrogens were substituted with relatively small methyl groups regardless of the substitution at the para position (entries 7−10). This type of modification is extremely useful for the construction of stable NHC ligands and opens a potential pathway to chiral fluorous NHC ligands in analogy to ref 10b. When we attempted to further increase the steric hindrance by introducing a bulkier isopropyl group into both ortho positions, a surprising monoaddition product followed by oxidation, 3k, was formed as a mixture of two stereoisomers (entry 11, probably E/Z isomers on the more hindered CN bond). Similarly, when biacetyl-based starting diimine 1l was used, only a low yield of the monoaddition product, the unstable iminoamine 4l, was obtained (entry 10). The results are listed in Table 1. The relative configuration of diamines 2 was determined by X-ray analysis of mesitylenebased diamine 2h (see Figure 1), which crystallizes as a conglomerate. While in the crystal, the left perfluorinated chain in Figure 1 is ordered with typical chirality (in this case in the M configuration) and the right perfluorinated chain in Figure 1 is highly disordered, with both P and M configurations present. Bis(polyfluoroalkylated) diamine 2h and tetrakis(polyfluoroalkylated) diamine 2j were employed for the synthesis of both light and heavy fluorous analogues of Hoveyda−Grubbs second-generation precatalysts. The synthesis followed the improved methodology of Nolan et al., using cyclization of diamines 2 to dihydroimidazolium tetrafluoroborates 5,9c followed by anion metathesis to the respective chloride 6a (Scheme 2). Deprotonation of salts 5 or 6 with potassium tert-pentoxide13 (t-PenOK) and final ligand exchange of the in situ formed NHC ligands with the Hoveyda−Grubbs first-generation precatalyst (HG1). Alternatively, we used complex HG1F modified with a perfluorohexyl group in the alkoxybenzylidene ligand, which should improve both the activity and fluorophilicity8,14 of complexes 7 (Scheme 3). As we expected, precatalysts 7a and 7b modified with two or three fluorinated chains did not contain a sufficient number of fluorine atoms to provide heavy fluorous properties as indicated by the fluorous partitioning coefficient between perfluoro(methylcyclohexane) and toluene at 25 °C [Pi(FBS) values of 0.055 for complex 7a and 0.13 for complex 7b]. However, complex 7c, based on the heavy fluorous diamine 2j, had heavy fluorous properties as indicated by a Pi(FBS) of 1.1 [Pi(FBS) is given as the ratio of masses of the studied compound found in both phases; compounds with Pi(FBS) values of >1 are heavy fluorous]. Finally, to obtain a complex with extreme

Chart 1. Previously Synthesized Heavy Fluorous Ruthenium Precatalysts for Alkene Metathesis

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RESULTS AND DISCUSSION The reduction of sterically hindered diimines to diamines is a principal method for the synthesis of saturated NHC ligands.9 The analogous nucleophilic addition of the appropriate fluorinated organometallic reagent to the diimine attracted our attention as a chemically economic pathway. Moreover, the addition of tert-butyllithium or tert-butylmagnesium bromide to sterically hindered diimines was reported to proceed stereoselectively10 and was successfully used for the synthesis of chiral ruthenium catalysts.11 Although 2-(perfluoroalkyl)ethyllithium was successfully employed in addition to ketones, esters, and amides,12 its reaction with imines has not been reported. We found that 2(perfluorohexyl)ethyllithium, formed in situ from the corresponding fluoroalkyl iodide and tert-butyllithium at low temperatures, added smoothly to diimine 1a, which had been obtained from glyoxal and p-toluidine (Scheme 1). The reaction resulted in a good yield with low stereoselectivity, giving a mixture of both diastereoisomers (see entry 1 of Table 1). Analogous results were obtained for diimines 1b and 1c, which also contained para-substituted aryl moieties. The stereoselectivity slightly improved with the decreasing electron-donor capacity of the substituent in the para position (entries 2 and 3). Similarly, when one of the o-hydrogens was substituted with small methyl or isopropyl groups, the stereoselectivity of the addition was low but the stereoselectivity increased with the increasing bulkiness of the substituent (entries 4 and 5). However, substitution of the o-

Scheme 1. Addition of 2-(Perfluorohexyl)ethyllithium to Diimines 1

B


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Organometallics Table 1. Results of Addition of 2-(Perfluorohexyl)ethyllithium to Diimines 1 entry

reactant

R1

R2

R3

R4

steric hindrance

product

yielda

threo/erythrob

1 2 3 4 5 6 7 8 9 10 11 12

1a 1b 1c 1d 1e 1f 1g 1h 1i 1j 1k 1l

H H H Me i-Pr t-Bu Me Me Me Me i-Pr Me

H H H H H H Me Me Me Me i-Pr Me

Me MeO Cl H H H H Me t-BuPh2SiO C6F13CH2CH2 H Me

H H H H H H H H H H H Me

low low low low low medium medium medium medium medium high high

2a 2b 2c 2d 2e 2f 2g 2h 2i 2j 3k 4l

89 72 92 87 89 94 83 81 72 94 62c 31

60:40 62:38 81:19 70:30 81:19 >98:2 >98:2 >98:2 >98:2 >98:2 − −

a

Yield of the threo/erythro mixture. bThe ratio of stereoisomers was determined by 1H and 19F nuclear magnetic resonance (NMR) spectroscopy; their relative configuration was assigned on the basis of crystal structure of 2h, using the signals of CHN groups in 13C NMR spectra with the signals of the threo isomer upfield and the signals of the erythro isomers downfield. cTwo sets of NMR signals were observed with homogeneous TLC and MS, and both compounds were hence tentatively assigned as possible E/Z stereoisomers on the more hindered CN bond.

fluorophilicity, we exchanged the chloride ligands in complex 7a for long perfluoropolyoxaalkanoate ligands in analogy to ref 8, resulting in complex 8 (Scheme 4), which had an extremely Scheme 4. Synthesis of Heavy Fluorous Complex 8

Figure 1. ORTEP plot of bis(polyfluoroalkylated) diamine 2h showing the ordered (left) and disordered (right) perfluorinated chain.

Scheme 2. Synthesis of Imidazolium Salts 5 and 6 from Diamines 2 high fluorophilicity with a Pi(FBS) of 27 (compared to 0.3 for the complex with a nonfluorous NHC ligand),8 confirming our previous observation8 that perfluoropolyoxaalkyl chains are more productive in improving fluorophilicity than common perfluorinated chains. The structure of complex 7a was confirmed by X-ray analysis. The complex crystallizes as a racemate, and both polyfluoroalkyl chains are highly disordered (see Figure 2). The activity of fluorous precatalysts 7 was compared with that of the Hoveyda−Grubbs second-generation precatalyst (HG2) and tested in a model RCM reaction of diethyl allylmethallylmalonate [DEAMM (see Figure 3)]. With an increasing number of polyfluoroalkyl chains in the order HG2 → 7a → 7c, the initial rate decreased, whereas the modification of 7a with a perfluoroalkyl chain (complex 7b) resulted in a relatively higher activity. In this moderately demanding catalytic process, full conversion was achieved for all studied catalysts. The RCM of diethyl dimethallylmalonate (DEDMM) represents a real challenge for ruthenium metathesis catalysts with the highly active precatalyst HG2 achieving 58% conversion at 70 °C.2b Therefore, several specially tailored catalysts were developed with minimized steric hindrance in the NHC ligand, which allowed the achievement of nearly complete conversion of DEDMM;15 the drawback was either challenging synthesis, and chromatographic separation15a or lower stability (e.g., ref 15b). As another solution, the use of a special perfluoroaromatic solvent resulted in the improved

Scheme 3. Synthesis of Ruthenium Complexes 7

C


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Organometallics

Figure 4. Kinetics of RCM of DEDMM (0.15 M solution) catalyzed with complexes HG2, 7a, and 7c (1H NMR, toluene-d8, 110 °C, 5 mol % catalyst).

layer with product was separated showed minimal loss of catalytic activity and little leaching of the active catalyst to the nonfluorous layer (see Table 2). Table 2. Recycling Experiment with Complex 7c

Figure 2. ORTEP plot of complex 7a containing highly disordered perfluorinated chains.

cycle conversion (%)

1 86

2 85

3 84

4 84

5 81

Gladysz et al. noted that the simple measurement of a high conversion rate for a catalytic reaction is not sufficient to confirm that the active catalyst is recycled and that the rate of the reaction in individual cycles should remain approximately constant. Moreover, the reaction conditions in early cycles should not reach full conversion too early compared to the sampling time.16 Hence, we analyzed the composition of the crude reaction mixture using 1H nuclear magnetic resonance (NMR) spectroscopy after 15, 30, and 45 min in the first and last catalytic cycle and found that it complied with all of the requirements described above (see Figure 5). Even in the last cycle, complete conversion of the metathesis was achieved after 12 h in a manner analogous to that shown in to Figure 4. In summary, we developed a stereoselective synthesis of polyfluoroalkylated diamines, from which both light and heavy fluorous alkene metathesis precatalysts were obtained, which had catalytic activity and stability comparable to or only slightly worse than those of highly active commercial catalysts. Our procedure can serve as an entry to chiral metathesis

Figure 3. Kinetics of RCM of DEAMM (0.15 M solution) catalyzed with complexes HG2, 7a, 7b, and 7c (1H NMR, CD2Cl2, 25 °C, 5 mol % catalyst).

catalytic activity of HG2 and other precatalysts.15c−e We were surprised that simply increasing the reaction temperature to 110 °C improved the extent of conversion with HG2, reaching 72%. Under these harsh conditions, complex 7a had comparable activity with a 74% conversion of DEDMM; the conversion rate of the tetrakis(polyfluoroalkylated) complex 7c was lower, but it was still significantly active (54% conversion) (see Figure 4). To evaluate the recyclability of the heavy fluorous catalyst 7c in the RCM of DEAMM, we first attempted to employ a standard solvent system, perfluoro(methylcyclohexane) with toluene. However, the solubility of 7c in both solvents at room temperature is rather low. We therefore searched for a better fluorous/nonfluorous solvent combination and finally found that a mixture of HFE 7100 (methyl perfluorobutyl/ perfluoroisobutyl ether) and dichloromethane forms two layers below −15 °C and that 7c has excellent solubility in the fluorinated solvent. Five repeated cycles in which the substrate in dichloromethane was added to 7c in HFE 7100, the metathesis was performed for 1 h at 30 °C, the homogeneous mixture was cooled to −25 °C, and the upper dichloromethane

Figure 5. Kinetics of recycling experiments (first and fifth cycles) of RCM of DEAMM (0.15 M solution) catalyzed with complex 7c (1H NMR, 2:1 CH2Cl2/HFE 7100, 30 °C, 5 mol % catalyst). D


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Organometallics precatalysts, as well as to various fluorous applications, for example, in flow chemistry. Moreover, the fluorous catalyst formed from precatalyst 7c was successfully recycled, which represents the first known application of heavy fluorous separation techniques in alkene metathesis.

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fumehood equipped with a ceramic desk. Less reactive organolithium reagents (n-BuLi) gave significantly poorer yields. General Procedure for the Addition of 1H,1H,2H,2HPerfluorooctyl Iodide to Diimines 1. To a solution of 1H,1H,2H,2H-perfluorooctyl iodide (3−6 equiv) and dry Et2O (60 mL) was added a 1.7 M solution of tert-butyllithium in pentane (6−12 equiv) at −78 °C. After the mixture had been stirred for 20 min at −78 °C, the solid diimine 1 (1 equiv) was added portionwise. The reaction mixture was stirred for 4 h and then slowly warmed to −30 °C and the reaction quenched with a saturated solution of ammonium chloride (1 mL). Water (20 mL) was added; an organic layer was separated, and the aqueous layer was extracted with diethyl ether (3 × 15 mL). The combined organic layers were dried over anhydrous MgSO4 and filtered; the solvents were removed with a vacuum rotary evaporator. The crude product was purified by flash column chromatography (hexane/DCM) to yield diamine 2, diimine 3, or iminoamine 4. 1,1,1,2,2,3,3,4,4,5,5,6,6,13,13,14,14,15,15,16,16,17,17,18,18,18-Hexacosafluoro-N,N′-bis(4-methylphenyl)octadecane9,10-diamine (2a). According to the general procedure, 1H,1H,2H,2H-perfluorooctyl iodide (2.41 g, 5.08 mmol), a 1.7 M solution of tert-butyllithium in pentane (6.35 mL, 10.79 mmol), and diimine 1a (0.30 g, 1.27 mmol) gave the mixture of threo and erythro isomers of diamine 2a (1.05 g, 88.7%, yellow oil, 60:40 threo/erythro) after purification by column chromatography (eluent, 4:1 hexane/ DCM). 1,1,1,2,2,3,3,4,4,5,5,6,6,13,13,14,14,15,15,16,16,17,17,18,18,18-Hexacosafluoro-N,N′-bis(4-methoxyphenyl)octadecane9,10-diamine (2b). According to the general procedure, 1H,1H,2H,2H-perfluorooctyl iodide (1.59 g, 3.35 mmol), a 1.7 M solution of tert-butyllithium in pentane (4.30 mL, 7.27 mmol), and diimine 1b (0.27 g, 1.01 mmol) gave the mixture of threo and erythro isomers of diamine 2b (0.67 g, 71.7%, pale yellow oil, 62:38 threo/ erythro) after purification by column chromatography (CHCl3). N,N′-Bis(4-chlorophenyl)-1,1,1,2,2,3,3,4,4,5,5,6,6,13,13,14,14,15,15,16,16,17,17,18,18,18-hexacosafluorooctadecane9,10-diamine (2c). According to the general procedure, 1H,1H,2H,2H-perfluorooctyl iodide (3.42 g, 7.22 mmol), a 1.7 M solution of tert-butyllithium in pentane (8.50 mL, 14.43 mmol), and diimine 1c (0.40 g, 1.44 mmol) gave the mixture of threo and erythro isomers of diamine 2c (1.30 g, 92.5%, light yellow oil, 81:19 threo/ erythro) after purification by column chromatography (4:1 hexane/ DCM). 1,1,1,2,2,3,3,4,4,5,5,6,6,13,13,14,14,15,15,16,16,17,17,18,18,18-Hexacosafluoro-N,N′-bis(2-methylphenyl)octadecane9,10-diamine (2d). According to the general procedure, 1H,1H,2H,2H-perfluorooctyl iodide (1.81 g, 3.81 mmol), a 1.7 M solution of tert-butyllithium in pentane (4.90 mL, 8.25 mmol), and diimine 1d (0.3 g, 1.27 mmol) gave the mixture of threo and erythro isomers of diamine 2d (1.03 g, 87.0%, white solid, 70:30 threo/erythro) after purification by column chromatography (4:1 hexane/DCM). 1,1,1,2,2,3,3,4,4,5,5,6,6,13,13,14,14,15,15,16,16,17,17,18,1 8 ,1 8 - H e x a c os a fl uo ro - N , N ′ - b i s ( 2 - i s o p r o p y l p h e n yl ) octadecane-9,10-diamine (2e). According to the general procedure, 1H,1H,2H,2H-perfluorooctyl iodide (1.81 g, 3.81 mmol), a 1.7 M solution of tert-butyllithium in pentane (4.90 mL, 8.25 mmol), and diimine 1e (0.30 g, 1.27 mmol) gave the mixture of threo and erythro isomers of diamine 2e (1.03 g, 91.7%, yellow oil, 81:19 erythro/threo) after purification by column chromatography (4:1 hexane/DCM). N,N′-Bis(2-tert-butylphenyl)-1,1,1,2,2,3,3,4,4,5,5,6,6,13,13,14,14,15,15,16,16,17,17,18,18,18-hexacosafluorooctadecane9,10-diamine (2f). According to the general procedure, 1H,1H,2H,2H-perfluorooctyl iodide (2.96 g, 6.24 mmol), a 1.7 M solution of tert-butyllithium in pentane (7.35 mL, 12.48 mmol), and diimine 1f (0.50 g, 1.56 mmol) gave threo-diamine 2f (1.03 g, 94.6%, yellow oil) after purification by column chromatography (4:1 hexane/ DCM). N,N′-Bis(2,6-dimethylphenyl)-1,1,1,2,2,3,3,4,4,5,5,6,6,13,13,14,14,15,15,16,16,17,17,18,18,18-hexacosafluorooctadecane9,10-diamine (2g). According to the general procedure, 1H,1H,2H,2H-perfluorooctyl iodide (2.15 g, 4.54 mmol), a 1.7 M solution of tert-butyllithium in pentane (5.70 mL, 9.65 mmol), and

EXPERIMENTAL SECTION

Temperature data were uncorrected. NMR spectra were recorded with a Varian MercuryPlus spectrometer or with an Agilent 400-MR DDR2 spectrometer. For the Varian MercuryPlus spectrometer, 1H NMR spectra were recorded at 299.97 MHz, 13C NMR spectra were recorded at 75.44 MHz using residual deuterated solvent signals as the internal standards, and 19F NMR spectra were recorded at 282.23 MHz using CCl3F as the internal standard. For the Agilent 400-MR DDR2 spectrometer, 1H NMR spectra were recorded at 399.94 MHz, 13 C NMR spectra were recorded at 100.58 MHz, and 19F NMR spectra were recorded at 376.29 MHz. Chemical shifts are given in parts per million and coupling constants in hertz. Mass spectra (ESI and APCI) were measured with a LCQ Fleet (Finnigan) instrument and HRMS spectra (ESI, APCI, and FAB) with an LTQ Orbitrap XL (Thermo Fisher Scientific) or ZAB-EQ (VG Analytical) instrument. Elemental analysis of highly fluorinated compounds, including perfluoroalkylated ponytail derivatives, is frustrated by the poor combustion of such species,17 which can be overcome only with specialized analytical instrumentation.18 Unsatisfactory analysis was found even for single perfluoroalkyl chains, which (as expected)17a worsened with an increasing fluorine content.19 Consistent with standard practice in heavy fluorous chemistry, compound identity and purity were gauged from HRMS data and detailed NMR analysis (see the Supporting Information for spectra).20 All reactions were performed in a dry inert atmosphere (Ar) in oven-dried flasks. In the reactions including ruthenium catalysts, solid compounds were introduced into the reaction flasks in a glovebox. Perfluoro-3,6,9-trioxadecanoic acid was purchased from Apollo Scientific. (Dichloro)(2-isopropoxybenzylidene)(triphenylphosphine)ruthenium(IV) (HG1, Hoveyda−Grubbs first-generation catalyst), tert-butyllithium (1.7 M solution in pentane), potassium tert-pentoxide (1.7 M solution in toluene), triethyl orthoformate, and ammonium tetrafluoroborate were purchased from Sigma-Aldrich. 1H,1H,2H,2HPerfluorooctyl iodide was kindly donated by Atochem and HFE 7100 liquid by 3M. 4-Iodo-2,6-dimethylaniline was obtained according to the method described in ref 21 and 4-[(tert-butyldiphenylsilyl)oxy]2,6-dimethylaniline according to the method described in ref 22. N,N′Bis(4-methylphenyl)ethane-1,2-diimine (1a), N,N′-bis(4methoxyphenyl)ethane-1,2-diimine (1b), N,N′-bis(4-chlorophenyl)ethane-1,2-diimine (1c), and N,N′-bis(2-methylphenyl)ethane-1,2diimine (1d) were prepared according to the method described in ref 23. N,N′-Bis(2-isopropylphenyl)ethane-1,2-diimine (1e) was prepared according to the method described in ref 24. N,N′-Bis(2tert-butylphenyl)ethane-1,2-diimine (1f) and N,N′-bis(2,6dimethylphenyl)ethane-1,2-diimine (1g) were prepared according to the method described in ref 25. N,N′-Bis(2,4,6-trimethylphenyl)ethane-1,2-diimine (1h) was prepared according to the method described in ref 26. N,N′-Bis(2,6-diisopropylphenyl)ethane-1,2diimine (1k) and N,N′-bis(2,4,6-trimethyl-phenyl)butane-2,3-diimine (1l) were prepared according to the method described in ref 27. (Dichloro)[2-isopropoxy-5-(perfluorohexyl)benzylidene](triphenylphosphine)ruthenium(IV) (HG1F) was synthesized according to the method described in ref 4c and silver(I) perfluoro-3,6,9trioxadecanoate according to that described in ref 4c. Diethyl allylmethallylmalonate and diethyl dimethallylmalonate were obtained according to the method described in refs 28 and 29. Hexane and dichloromethane were dried over CaH2, distilled, stored over molecular sieves, and degassed prior to use, and diethyl ether was distilled from the solution of diphenyl ketyl radical and degassed. Caution: tert-Butyllithium is a pyrophoric liquid that reacts violently and exothermically with moisture in air. It must be handled in strict accordance with safety regulations using using proper needle and syringe techniques. These experiments were performed on a small scale, in a E


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Organometallics

General Procedure for the Preparation of Ruthenium Complexes 7. A flask was charged with salt 5 or 6 and anhydrous degassed hexane (6 mL). Potassium tert-pentoxide (1.7 M solution in toluene) was added, and the resulting mixture was stirred at room temperature for 1 h. To the resulting brownish solution was added ruthenium complex HG1 or HG1F in one portion. The flask was equipped with a reflux condenser and removed from the glovebox, and the reaction mixture was refluxed for 2.5 h. Solid CuCl was added in one portion, and the resulting mixture was refluxed for an additional 1.5 h. The reaction mixture was then evaporated to dryness with a small amount of silica gel, and the resulting dark brown-green solid was purified by column chromatography (1:1 hexane/DCM eluent) to yield complex 7. [trans-4,5-Bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)1,3-bis(2,4,6-trimethylphenyl)imidazolidin-2-ylidene](dichloro)(2-isopropoxybenzylidene)ruthenium(IV) (7a). According to the general procedure, salt 6a (0.312 g, 0.301 mmol), potassium tert-pentoxide (0.19 mL, 0.32 mmol), Hoveyda−Grubbs first-generation catalyst (HG1, 0.150 g, 0.250 mmol), and solid CuCl (0.044 g, 0.45 mmol) gave complex 7a (0.287 g, 87.2%, dark green crystals, mp 99−102 °C). [trans-4,5-Bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)1,3-bis(2,4,6-trimethylphenyl)imidazolidin-2-ylidene](dichloro)[2-isopropoxy-5-(1,1,2,2,3,3,4,4,5,5,6,6,6-tridecafluorohexyl)benzylidene]ruthenium(IV) (7b). According to the general procedure, salt 6a (0.357 g, 0.331 mmol), potassium tertpentoxide (0.21 mL, 0.35 mmol), a perfluorohexylated Hoveyda− Grubbs first-generation catalyst analogue (HG1F, 0.240 g, 0.274 mmol), and solid CuCl (0.050 g, 0.492 mmol) gave complex 7b (0.323 g, 75.5%, dark green solid, mp 164−165.5 °C). {trans-1,3-Bis[2,6-dimethyl-4-(3,3,4,4,5,5,6,6,7,7,8,8,8tridecafluorooctyl)phenyl]-4,5-bis(3,3,4,4,5,5,6,6,7,7,8,8,8tridecafluorooctyl)imidazolidin-2-ylidene}(dichloro)(2-isopropoxybenzylidene)ruthenium(IV) (7c). According to the general procedure, salt 5b (0.500 g, 0.286 mmol), potassium tertpentoxide (0.18 mL, 0.305 mmol), Hoveyda−Grubbs first-generation catalyst (HG1, 0.143 g, 0.238 mmol), and solid CuCl (0.043 g, 0.428 mmol) gave complex 7c (0.291 g, 61.6%, dark green crystals, mp 75.5−77.5 °C). [trans-4,5-Bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)1,3-bis(2,4,6-trimethylphenyl)imidazolidin-2-ylidene](2isopropoxybenzylidene)bis(perfluoro-3,6,9trioxadecanoyloxy)ruthenium(IV) (8). A flask was charged with ruthenium complex 7a (0.120 g, 0.091 mmol), silver(I) 3,6,9trioxaperfluorodecanoate (0.141 g, 0.200 mmol), and anhydrous degassed dichloromethane (3 mL). The reaction mixture was then stirred for 3 h at room temperature in the dark. The solution was filtered through Celite and evaporated to dryness to yield complex 8 (0.150 g, 79.6%, violet sticky solid). General Procedure for the Study of Catalytic Activity. An NMR tube was charged with precatalyst (5.0 μmol, 5 mol %) and solvent (CD2Cl2 or toluene-d8, 0.65 mL). The substrate [diethyl allylmethallylmalonate (25.3 mg, 0.100 mmol) or diethyl dimethallylmalonate (26.6 mg, 0.100 mmol] was added, and the mixture was stirred at 25 or 110 °C. The progress of the reaction was monitored by 1 H NMR spectroscopy. Example of Catalytic Activity Measurement. An NMR tube was charged with complex 7a (9.9 mg, 5.0 μmol) and toluene-d8 (0.65 mL). Diethyl dimethallylmalonate (26.6 mg, 0.100 mmol) was added, and the mixture was heated to 110 °C for 24 h and had a 74% rate of conversion to diethyl 3,4-dimethylcyclopent-3-ene-1,1-dicarboxylate as measured by 1H NMR spectroscopy. Recycling Experiment. A Schlenk flask was charged with complex 7c (6.0 mg, 3.0 μmol, 5 mol %) and HFE 7100 (1 mL), followed by the addition of a solution of DEAMM (15.4 mg, 60.5 μmol) in dichloromethane (2 mL). The mixture was heated to 30 °C for 1 h and cooled to −25 °C while being occasionally shaken. A two-phase system was formed, and the upper layer was removed. The bottom layer was heated to 30 °C; another portion of reactant solution (15.4 mg, 60.5 μmol in 2 mL of dichloromethane) was added, and the whole procedure was repeated four times. For kinetic measurements, 0.7 mL

diimine 1g (0.30 g, 1.14 mmol) gave threo-diamine 2g (0.90 g, 82.6%, white solid, mp 81−83 °C) after purification by column chromatography (4:1 hexane/DCM). 1,1,1,2,2,3,3,4,4,5,5,6,6,13,13,14,14,15,15,16,16,17,17,18,18,18-Hexacosafluoro-N,N′-bis(2,4,6-trimethylphenyl)octadecane-9,10-diamine (2h). According to the general procedure, 1H,1H,2H,2H-perfluorooctyl iodide (3.24 g, 6.84 mmol), a 1.7 M solution of tert-butyllithium in pentane (8.55 mL, 14.53 mmol), and diimine 1h (0.50 g, 1.71 mmol) gave threo-diamine 2h (1.36 g, 80.5%, white solid, mp 85−86 °C) after purification by column chromatography (4:1 hexane/DCM). N,N′-Bis{4-[(tert-butyldiphenylsilyl)oxy]-2,6-dimethylphenyl}-1,1,1,2,2,3,3,4,4,5,5,6,6,13,13,14,14,15,15,16,16,17,17,18,18,18-hexacosafluorooctadecane-9,10-diamine (2i). According to the general procedure, 1H,1H,2H,2H-perfluorooctyl iodide (4.60 g, 9.70 mmol), a 1.7 M solution of tert-butyllithium in pentane (11.40 mL, 19.40 mmol), and diimine 1i (1.25 g, 1.71 mmol) gave threo-diamine 2i (1.70 g, 71.9%, yellow oil) after purification by column chromatography (4:1 hexane/DCM). N,N′-Bis[2,6-dimethyl-4-(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)phenyl]-1,1,1,2,2,3,3,4,4,5,5,6,6,13,13,14,14,15,15,16,16,17,17,18,18,18-hexacosafluorooctadecane-9,10-diamine (2j). According to the general procedure, 1H,1H,2H,2H-perfluorooctyl iodide (3.96 g, 8.36 mmol), a 1.7 M solution of tert-butyllithium in pentane (9.80 mL, 16.7 mmol), and diimine 1j (2.00 g, 2.09 mmol) gave threo-diamine 2j (3.26 g, 94.3%, yellow solid) after purification by column chromatography (25:1 hexane/EtOAc). N-(2,6-Diisopropylphenyl)-1-(2,6-diisopropylphenylimino)5,5,6,6,7,7,8,8,9,9,10,10,10-tridecafluorodecane-2-amine (3k). According to the general procedure, 1H,1H,2H,2H-perfluorooctyl iodide (1.51 g, 3.19 mmol), a 1.7 M solution of tert-butyllithium in pentane (4.10 mL, 6.90 mmol), and diimine 1k (0.38 g, 1.01 mmol) gave diimine 3k (0.45 g, 61.7%, yellow oil) as a mixture of stereoisomers A and B in a 5:1 ratio after purification by column chromatography (4:1 hexane/DCM). 6,6,7,7,8,8,9,9,10,10,11,11,11-Tridecafluoro-3-methyl-2(2,4,6-trimethylphenylimino)-N-(2,4,6-trimethylphenyl)undecane-3-amine (4l). According to the general procedure, 1H,1H,2H,2H-perfluorooctyl iodide (1.88 g, 3.97 mmol), a 1.7 M solution of tert-butyllithium in pentane (5.10 mL, 8.61 mmol), and diimine 1l (0.35 g, 1.32 mmol) gave unstable iminoamine 4l (0.25 g, 30.8%, light yellow oil) after purification by column chromatography (4:1 hexane/DCM). General Procedure for the Preparation of Dihydroimidazolium Tetrafluoroborates 5. A mixture of diamine 2, NH4BF4 (∼10% molar excess), and CH(OEt)3 was heated to 125 °C and stirred for 15 h, during which the whole content became a solid. After cooling to room temperature, the mixture was triturated with Et2O (6 × 3 mL), and the residue was redissolved in acetone; the solvent was removed, and the resulting white solid was dried on a vacuum oil pump to yield dihydroimidazolium tetrafluoroborate 5. trans-4,5-Bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,3bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazolium Tetrafluoroborate (5a). According to the general procedure, diamine 2h (0.50 g, 0.51 mmol), NH4BF4 (0.061 g, 0.58 mmol), and CH(OEt)3 (1 mL) gave dihydroimidazolium salt 5a (0.53 g, 90%, white crystals, mp 159− 161 °C). trans-1,3-Bis[2,6-dimethyl-4-(3,3,4,4,5,5,6,6,7,7,8,8,8tridecafluorooctyl)phenyl]-4,5-bis(3,3,4,4,5,5,6,6,7,7,8,8,8tridecafluorooctyl)-4,5-dihydroimidazolium Tetrafluoroborate (5b). According to the general procedure, diamine 2j (0.76 g, 0.46 mmol), NH4BF4 (0.056 g, 0.53 mmol), and CH(OEt)3 (0.3 mL) gave dihydroimidazolium salt 5b (0.65 g, 80%, light yellow crystals, mp 148.5−150.5 °C). trans-4,5-Bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,3bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazolium Chloride (6a). Dihydroimidazolidium salt 5a (1.00 g, 0.92 mmol) was dissolved in MeOH (3 mL) and passed through a short column of ion exchange resin Amberlite 400. The column was washed with MeOH until no spot was visible via TLC under UV. The solvent was removed, and the resulting white solid was dried with a vacuum pump to yield product 6a (0.96 g, 99%, white crystals, mp 236−238 °C). F


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Organometallics

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of the crude homogeneous reaction mixture was transferred to an NMR tube, analyzed directly by 1H NMR spectroscopy at 30 °C using an external standard, and then returned back to the reaction mixture.

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ASSOCIATED CONTENT

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AUTHOR INFORMATION

* Supporting Information S

Layered arrangement of fluorous and nonfluorous domains for 2h and 7a, experimental and analytical details of synthesis of diimines 1h and 1j, analytical data for all synthesized compounds, and copies of 1H, 19F, and 13C NMR spectra. Crystallographic data have been deposited with the Cambridge Crystallographic Data Centre as CCDC 1023000 and CCDC 1023001 for 2h and 7a, respectively. Copies of data can be obtained, free of charge, upon application to CCDC, 12 Union Road, Cambridge CB2 1EZ, U.K. ([email protected]. uk). The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.organomet.5b00325. Corresponding Author

*E-mail: [email protected]. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was supported by the Grant Agency of the Czech Republic (110/13/0657) and specific university research (MSMT Grant 20/2014).

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REFERENCES

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Synthesis of Heavy Fluorous Ruthenium Metathesis Catalysts Using

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