Influences of Fluorine Substituents on Iminopyridine Fe(II)- and Co(II)-Catalyzed Isoprene Polymerization

A series of iminopyridine complexes of Fe(II) and Co(II) complexes bearing fluorinated aryl substituents were synthesized for the polymerization of isoprene. The structures of complexes 3a, 2b and 3b were determined by X-ray diffraction analysis. Complex 3a contained two iminopyridine ligands coordinated to the iron metal center forming an octahedral geometry, whereas 2b adopted a chloro-bridged dimer, and 3b featured with two patterns of cobalt centers bridged via chlorine atoms. Complexes 2b and 3b represented rare examples of chlorine bridged bimetallic Co(II) complexes. The fluorine substituents effects, particularly on catalytic activity and polymer properties such as molecular weight and regio-/stereo-selectivity were investigated when these complexes were employed for isoprene polymerization. Among the Fe(II)/methylaluminoxane (MAO) systems, the 4-CF3 substituted iminopyridine Fe(II) complex 1a was found as a highly active isoprene polymerization catalyst exhibiting the highest activity of 106 g·(mol of Fe)−1·h−1. The resultant polymer displayed lower molecular weight (Mn = 3.5 × 104 g/mol) and moderate polydispersity index (PDI = 2.1). Furthermore, the ratio of cis-1,4-/3,4 was not affected by the F substituents. In the series of Co(II)/AlEt2Cl binary systems, complexes containing electron-withdrawing N-aryl substituents (R = 4-CF3, 2,6-2F) afforded higher molecular weights polyisoprene than that was obtained by the complex containing electron-donating N-alkyl substituents (R = octyl). However, ternary components system, complex/MAO/[Ph3C][B(C6F5)4] resulted in low molecular weight polyisoprene (Mn < 2000) with high trans-1,4-unit (>95%).


Introduction
Synthetic polyisoprene displays significant interests in material application, which has been introduced to replace the natural rubber in some extent [1]. Polyisoprene can be obtained with diverse regio-and/or stereo-selectivities such as cis-1,4-/trans-1,4-/3,4-/1,2-polyisoprene. The physical properties are strongly related to the microstructure of polyisoprene. For instance, cis-1,4-polyisoprene shows similar characteristics particularly stereo and chemical compositions and thereby mechanical properties with the natural rubber which has been largely applied to tires [2]. High trans-1,4-polyisoprene is more alike to the natural gutta-percha [3], which is widely employed in

General Information
All manipulations of air and/or moisture sensitive compounds were performed using standard Schlenk technique. Toluene, dichloromethane, tetrahydrofuran (THF) and hexane were purchased from Sinopharm Chemical Reagent (Shanghai, China), dried over sodium benzophenone ketyl (toluene, THF) or calcium hydride (CH 2 Cl 2 , hexane) and distilled under an argon atmosphere prior to use. The progress of the organic reactions was monitored by thin layer chromatography (TLC) using 0.2 mm Macherey-Nagel silica gel precoated plates (POLYGRAM SILG/UV254, haoranbio, Shanghai, China). 1 H and 13 C NMR spectra were recorded on a Bruker Avance III 400 MHz spectrometer (Bruker, Karlsruhe, Germany) using CDCl 3 (CIL, Andover, MA, USA) as solvent and trimethylsilane (TMS; CIL, Andover, MA, USA) as internal reference. Chemical shifts and coupling constant are given in ppm and in Hz respectively. The abbreviations: s = singlet, d = doublet, t = triplet, m = multiplet were used to designate the multiplicities of signal. Attenuated total reflection-infrared (ATR-IR) spectroscopy was performed using Thermo Scientific Nicolet iN10 (Thermo Fisher Scientific Corporation, Waltham, MA, USA). Elemental analysis was carried out on Vario EL III elemental analyzer (Elementar Corporation, Hanau, Germany) at Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences (Shanghai, China). Mass spectra for new organic compounds were measured using maXis II of Bruker Daltonics Corporation (Bruker Daltonics Corporation, Billerica, MA, USA), while for Fe(II) and Co(II) complexes were recorded by ACQUITYTM UPLC & Q-TOF MS Premier (Waters, Milford, MA, USA) at Analytical Center of Shanghai Jiao Tong University (Shanghai, China). X-ray Diffraction data was collected on Smart 1000 diffractometer (Bruker, Karlsruhe, Germany) with Mo K-alpha X-ray source (λ = 0.71073 Å) at 150 K. The SUPERFLIP72 program was employed for dealing with the collected data and refinement of data was achieved through the SHELX-97 and OLEX2 programs. Molecular weights and polydispersity index (PDI) of polyisoprene were undertaken by gel permeation chromatography (GPC, Viscotek VE2001 GPC, Viscotek Corporation, Houston, TX, USA) at 35 • C using a PL2MB500A column in THF at a flow rate of 1 cm 3 ·min −1 ; 50 µL was injected using a Viscotek VE2001 GPC equipped with a Viscotek VE3580 Refractive Index detector using THF as the eluent. While high temperature gel permeation chromatography (HGPC, PL-GPC 220, Agilent Technologies, Palo Alto, CA, USA) was employed for polymerization using trichlorobenzene as the eluent and polystyrenes as standards. Isoprene was purchased from Aladdin Industrial Corporation (Shanghai, China), dried over CaH 2 and distilled prior to use. 1-(pyridin-2-yl)-N-(4-(trifluoromethyl)phenyl)methanimine (L1), (E)-N-(2,6-difluorophenyl)-1-(pyridin-2-yl)methanimine (L2), (E)-2,4,4-Trimethyl-N-(pyridin-2ylmethylene)pentan-2-amine (L4) and 1-(pyridin-2-yl)-N-(2,4,6-(triphenyl)phenyl)methanimine (L5) are not commercially available and can be prepared using reported procedure [29][30][31][32][33]. Complexes 4a (C 14 H 22 Cl 2 FeN 2 ), 5a (C 60 H 44 Cl 4 Fe 2 N 4 ) and 4b (C 14 H 22 Cl 2 CoN 2 ), 5b (C 30 H 22 Cl 2 CoN 2 ) were synthesized using reported routes [27,28]. All other reagents were purchased from commercial sources and used without further purification. Due to the paramagnetic properties of Fe(II) and Co(II) complexes, these complexes were mainly characterized by elemental analyses, TOF-MS-ES+ (the concrete graphical data see Supplementary Materials, Figures S5-S10) and Attenuated total reflection-infrared spectroscopy (ATR-IR) unless otherwise noted. Note: The L1, L2, L4 and L5 are known compounds and can be prepared using reported procedure. However, the procedure adopted for the synthesis of L3 is slightly different in the context of purification process and can be prepared in the following procedure. To a solution of 2-pyridinecarboxaldehyde (1.00 g, 0.89 mL, 6.80 mmol) in CH 2 Cl 2 (10 mL), 2,4,6-trifluoroaniline (0.72 g, 6.73 mmol) was added. The reaction mixture was heated to reflux for 12 h with azeotropic removal of water using a Dean-Stark trap. On completion of the reaction (checked by TLC), the reaction mixture concentrated under reduced pressure and the residue was purified by recrystallization using hexane at 0 • C afforded L3 as colorless solid (0.81 g, 50.5% yield).

General Procedure for Isoprene Polymerization
In a typical experiment, the reactor was heated, dried in a vacuum, and recharged with nitrogen for three times. When the reactor cooled down, an aluminum cocatalyst, toluene (5 mL), isoprene (2 mL, 20 mmol) and a solution of Fe(II) or Co(II) complexes (8 µmol) in 1 mL CH 2 Cl 2 added into the reactor in sequence manner. The reaction was employed for 2 h and was then quenched with a diluted HCl solution of methanol (MeOH/HCl = 50/1). The polymer was collected by filtration and washed with ethanol several times and dried at room temperature for 24 h under vacuum.
For ternary system, a slightly different method of polymerization was used. A 25 mL Schlenk reactor was heated, dried in a vacuum, and recharged with nitrogen for three times. On cooling the reactor, Fe(II) or Co(II) complexes (8 µmol) in 2 mL toluene, MAO (40 µmol) in 1 mL toluene were added. The reaction mixture was stirred for 2 min and [Ph 3 C][B(C 6 F 5 ) 4 ] (7.4 mg, 8 µmol) was added as a solution in toluene (2 mL). The reaction mixture was stirred for 2 min and isoprene (1 mL, 10 mmol) was added and stirred for 2 h at room temperature. The polymerization was quenched with a diluted HCl solution of methanol (MeOH/HCl = 50/1). The polymer was collected by filtration and washed with ethanol several times and dried at room temperature for 24 h under vacuum.

The Synthesis and Characterization of Iminopyridine Ligands and Corresponding Fe(II) and Co(II) Complexes
Ligand precursors were prepared by the condensation reaction of 2-pyridinecarboxaldehyde with arylamine in dichloromethane at refluxed temperature (Scheme 2). The desired compounds were purified through recrystallization in hexane (L1, L3), reduced pressure distillation (L4) or column chromatography (L2, L5). Ligands L1, L2, L4, and L5 were confirmed according to the references [29][30][31][32][33] and novel ligand L3 was characterized by 1 H NMR, 13  The corresponding iminopyridine Fe(II) and Co(II) dichloride complexes containing fluorine substituents were synthesized by a reaction of the resulting iminopyridine ligand with one equivalent of anhydrous FeCl 2 in CH 2 Cl 2 or anhydrous CoCl 2 in THF, respectively (Scheme 2). These complexes were characterized by ATR-IR, TOF-MS-ES+-and elemental analysis.
The structures of complexes 3a, 2b, and 3b were further characterized by X-ray crystallographic analysis. The ORTEP drawings of Fe(II) complex 3a and Co(II) complexes 2b and 3b are shown in Figure 1 (Concrete crystallographic data see Supplementary Materials, Tables S7-S10). For these complexes, the ligands system adopts a cisoid conformation, which permits both pyridine nitrogen atoms and imine nitrogen atoms to coordinate to the metal atoms. Single crystal of Fe(II) complex 3a (See Figure 1a) was obtained by recrystallization from concentrated acetonitrile solutions of complex 3a layered with hexane at −35 • C. The solid state crystal structure analysis shows that the complex 3a adopts distorted octahedral coordination geometry around the iron metal formed by two iminopyridine ligands and two terminal chlorine atoms. And the imine nitrogen atom (N2) and Cl2 occupy the axial coordination sites and the axial N2-Fe1-Cl2 angle exhibits a small non-linearity (167.46 (12) [27], which may be supported that electron-withdrawing substituent (2,4,6-3F group in 3a) reduces the electron density around the metal center and affects binding interaction between the metal and the coordination donor as well as the opening environment near the metal center. Complex 3a features a smaller N1-Fe1-N2 bond angle of 72.68 (17)  Complex 3b (See Figure 1c) features a chloride-bridged dinuclear structure as one cobalt ion is in a distorted octahedral coordination geometry while the other is in a distorted tetrahedral environment. In Co1 metal center, two equivalent iminopyridine ligands coordinated with it, the equatorial plane is occupied by pyridine nitrogen atom (N1, N3), imine nitrogen atom N2 and Cl1. The  (7) Å] are consistent with the typical characters of C=N double bond although it is relatively shorter than those in the literature [40][41][42]. The Co1-Co2 distance of 3.367(8) Å is longer than those found in some dicobalt complexes and carbonyl cobalt compounds [43,44].

Polymerization of Isoprene with Fe(II) Catalysts
A variety of alkylaluminum reagents (MAO, Al(i-Bu) 3 , AlEt 3 , AlEt 2 Cl, AlEtCl 2 , and EASC (Ethylaluminum sesquichloride)) were screened as a cocatalyst in isoprene polymerization (See Supplementary Materials, Table S1) and MAO was chosen as the effective cocatalyst. The polymerization results are summarized in Table 1 (NMR Spectra and GPC characterizations of the representative polyisoprene see Supplementary Materials, Figures S11-S16 and S25-S29). The fluorinated aryl moiety significantly influenced the catalytic performances of the complexes. The fluorinated aryl-substituted complexes 1a-3a produced polymers at higher yields (32.7-99.0%) than the reported complexes 4a-5a (10.9-21.1%) under the same condition. In Fe(II)/MAO binary system, complex 1a bearing 4-CF 3 moiety exhibited the highest yield but with a relatively lower molecular weight and broad molecular weight distribution ( Table 1, entry 1). Complex 2a having 2,6-2F moiety gave slightly lower activity with a higher molecular weight and narrow molecular weight distribution (Table 1, entry 2). In contrast, complex 3a with 2,4,6-3F showed the lowest activity with a higher molecular weight and narrower molecular weight distribution (Table 1, entry 3). It is proposed that introducing electron withdrawing group can reduce the electron density on the metal center and the increased Lewis acidic character facilitates the coordination of isoprene monomer, leading to the increment of chain propagation rate. The lower molecular weight of polyisoprene generated with complex 1a may be ascribed to a faster chain transfer process. Furthermore, in Fe(II)/MAO system, the ratio between cis-1,4-/3,4-units was not affected by the F substituents. Although this difference is not fully understood, it is clear that the cocatalyst may play an important role in determining the stereoselectivities.
Subsequently, complex 1a was used as a model catalyst to study the Al/M ratio and catalyst loading influence on the isoprene polymerization. Gratifyingly, complex 1a can polymerize isoprene in full conversion within 10 min under our typical condition (See Supplementary Materials, Table S2, entry 1). Because of the poor solubility of the resultant polyisoprene, the molecular weight and molecular weight distribution cannot be obtained via GPC measurement. Decreasing the Al/M ratio from to 500 to 10 resulted in a steady decline of obtained polymer yield but with a narrow PDI and an increase of the molecular weight. At Al/M = 500, the stereoselectivity of the resultant polyisoprene was cis-1,4-/3,4-= 54/46. Decreasing the Al/M ratio and catalyst loading or increasing the Al/M ratio with lower catalyst loading resulted in an inverse of the cis-1,4-/3,4ratio (See Supplementary  Materials, Table S2, entries 2, 3 and 6, 7; representative NMR spectra see Supplementary Materials, Figures S23 and S24). At very low Al/M ratio (Al/Fe = 10), prolonging reaction time did not increase the polymer yield, which indicated a rapid deactivation process (See Supplementary Materials, Table S2, entries 3-5).
At Al/M = 500, the catalyst loading of complex 1a can even be reduced to 1 µmol to give reasonable yield of polyisoprene (See Supplementary Materials, Table S2, entry 6). Increasing reaction time resulted in little improvement on the polymer yield (See Supplementary Materials, Table S2, entries 8 and 9), which produced polyisoprene in 64.9% yield with a bimodal character. One active species generated high molecular weight of polyisoprene, the other generated low molecular weight of polyisoprene with narrow PDI. Prolonging the reaction time to 40 min and 1 h did not increase the yield of polyisoprene, which implied active species were rather sensitive and short-lived. However, based on the molecular weight of the obtained polyisoprene, it seems that the bimodal active species turned to unimodal species, which produced high molecular weight of polyisoprene along the reaction time [See Supplementary Materials, Table S2, entry 6: 9.3 × 10 4 /1700 (10 min), entry 8: 4.4 × 10 4 (40 min), and entry 9: 21.1 × 10 4 (1 h)]. Increasing the ratio of Al/Fe from 500 to 1000, polyisoprene is obtained in 69.0% yield (See Supplementary Materials, Table S2, entry 7). It was concluded that large excess of MAO did not enhance the polymerization activity and stereoselectivity, while molecular weight and PDI showed an increasing trend.
For complex 1a, at very low catalyst loading (1 µmol), we observed an increase of polymer yield when Al/M ratio was increased from 500 to 1000 (See Supplementary Materials, Table S2, entries 6 and 7). Therefore, we systematically investigated higher Al/M ratio on all the complexes 2a-5a (See Supplementary Materials, Table S3). The results showed that the polyisoprene yields increased with the increase of Al/Fe ratio while stereoselectivity changed little when novel fluoro-substituted complexes 2a and 3a were employed. The increase of polyisoprene yield was highlighted by full conversion achieved in 2a system with an obvious increase of molecular weight (M n = 22.3 × 10 4 ). Similarly, at large excess of MAO, 4a and 5a showed a same trend in the yields while multi-modal polyisoprene was generated.

Polymerization of Isoprene with Co(II) Catalysts
Encouraged by the results in Fe(II) complexes catalyzed isoprene polymerization, further studies were carried out in Co(II) complexes using various common alkylaluminum reagents as cocatalysts. In iminopyridine Co(II)-catalyzed isoprene polymerization, MAO, Al(i-Bu) 3 , and AlEt 3 showed an adverse effect on polymerization of isoprene (See Supplementary Materials, Table S4). However, AlEt 2 Cl was effective as cocatalyst. When the ratio of Al/Co was 500, no polymer was observed. Polymer appeared with the decrease of Al/Co ratio (See Supplementary Materials, Table S5). After optimization of Al/M ratio, Al/M = 10 was chosen as the optimal condition in Co(II)/AlEt 2 Cl binary system (See Table 2; NMR Spectra and GPC characterizations of the representative polyisoprene see Supplementary Materials, Figures S17, S18 and S30-S34). Co(II) complexes 1b and 2b containing electron-withdrawing aryl substituents afforded polymers with higher molecular weights at moderate yields ( Table 2, entries 1 and 2) than those by the complex Co(II) containing electron-donating alkyl substituents ( Table 2, entry 4: R = octyl). This is similar with the trend observed in the Fe(II)/MAO systems. At this stage, there is no correlation between the electronic effect of the complexes and the resultant polyisoprene, especially in the stereoselectivity.

The Ternary System of Iminopyridine Fe(II) and Co(II)-Catalyzed Isoprene Polymerization
Raynaud et al. [27] reported a significant effect of introduction of a dealkylating reagent ([Ph 3 C][B(C 6 F 5 ) 4 ]) to the activated Fe(II) complexes using Al(i-Bu) 3 and AlEt 3 as cocatalyst. In our system, MAO/[Ph 3 C][B(C 6 F 5 ) 4 ] cocatalysts were proved to be effective to generate polyisoprene (See Table 3; Screening experiment with various cocatalysts see Supplementary Materials, Table S6; NMR Spectra and GPC characterizations of the representative polyisoprene see Supplementary Materials, Figures S19-S22 and S35-S43). The Fe(II) complexes having fluorine substituents showed high activities (Table 3, entries 1-3). Furthermore, the ratio between trans-1,4-/3,4units was not affected by the substituents pattern. It is assumed that the cocatalysts play an important role in determining the stereoselectivity. In Co(II)-catalyzed system, the fluorinated aryl moiety is electronically more withdrawing than the alkyl moiety, which can reduce the electron density on the metal center, leading to better monomer coordination and faster chain propagation. This is supported by the fact that Co(II) complex 3b bears the strongest electron-withdrawing substituent and displays the highest yield (71.8%). In addition, the molecular weight of polyisoprene obtained by fluorine-substituted complexes 1b-3b is lower than the bulkier alkyl-substituted Co(II) complexes (4b) (R = octyl) ( Table 3, 1400~1600 vs. 1600). Probably, the steric environment of the alkyl moiety retards chain transfer reaction more effectively than less hindered fluorine substituted aryl moiety. We have to mention that as for the resultant polyisoprene, there were miscellaneous peaks in aromatic areas from 1 H NMR, which was speculated as by-product of toluene involved Friedel-Crafts reaction [45,46]. The change in stereoselectivity from binary system (cis-1,4-unit and 3,4-unit) to ternary system (trans-1,4-unit and 3,4-unit) is solely based on the cocatalysts. It is difficult to conclude the selectivity determining step because of the complexity of the cocatalyst and lack of reactive intermediates isolation. Furthermore, the isoprene coordination mode s-cis or s-trans (As is known for monoalkenes, the Cossee-Arlman mechanism is the main pathway for the formation of C-C bonds in the polymerization of alkenes. Such mechanism is true of conjugated diene polymerization by homogeneous single site catalysts involves two steps, namely coordination of the incoming monomer to the catalyst active site and subsequent monomer insertion into a metal-carbon bond. However, the polymerization mechanism for conjugated dienes presents several peculiar aspects, mainly related to the type of bond between the transition metal of the catalyst and the growing chain. This bond is of a σ type in monoalkene polymerizations, but is of the allylic type (η 3 ) in conjugated diene polymerizations. Furthermore, the conjugated diene monomer can coordinate to the metal center assuming different conformations and hapticities: s-cis-η 4 (cis conformation around the single bond and coordination of the two double bonds), s-trans-η 4 (trans conformation around the single bond and coordination of the two double bonds), or s-trans-η 2 (trans conformation around the single bond and coordination of only one double bond. More mechanistic details see Supplementary Materials Figure S45) [47], migratory insertion into an η 2 -or η 4 -coordinated isoprene, generation of synand anti-M-allyl intermediates, synto anti-rearrangements of the M-allyl complexes may all be relevant for selectivity [48][49][50].

Conclusions
In summary, we have investigated novel fluorinated aryl substituted iminopyridine Fe(II) and Co(II) complexes in isoprene polymerization. Higher polymer yield, high molecular weight and similar stereoselectivity (cis-1,4-/3,4-unit ≈ 1:1) were obtained when binary Fe/MAO system was employed. This is the same trend with Co/AlEt 2 Cl excepted the stereoselectivity (cis-1,4-/3,4-unit ≈ 7:3). In general, Fe(II) complexes exhibited higher activities than analogous Co(II) complexes. However, Co(II) complexes showed higher cis-1,4 selectivity than Fe(II) complexes under the same condition. When a dealkylating reagent [Ph 3 C][B(C 6 F 5 ) 4 ] was introduced in isoprene polymerization, low molecular weight (M n = 1200~1700) and high trans-1,4 polyisoprene (>95%) were prepared using either Fe(II) or Co(II) catalysts and MAO cocatalyst. In such system, the differences of catalytic behaviors between Fe(II) and Co(II) systems were not obvious. These studies demonstrated that iminopyridine complexes containing fluorine substituents tended to enhance the catalytic activity and led to a relatively higher yield of polyisoprene. Fe(II) complex (1a) containing CF 3 substituent represented a rare example of highly active Fe(II) catalyst and relatively low catalyst loading (1 µmol) in isoprene polymerization. In addition, it is observed that less amount of AlEt 2 Cl was required to initiate an effective isoprene polymerization in Co/AlEt 2 Cl binary system. The stereoselectivity of polyisoprene was strongly dependent on the cocatalysts type and metal center. Further studies aiming at exploring the controllable polymerization using iminopyridine complexes and mechanistic studies are now in progress in our laboratory.