Ru-Catalyzed Repetitive Batch Borylative Coupling of Oleﬁns in Ionic Liquids or Ionic Liquids / scCO 2 Systems

: The ﬁrst, recyclable protocol for the selective synthesis of ( E )-alkenyl boronates via borylative coupling of oleﬁns with vinylboronic acid pinacol ester in monophasic (cat@IL) or biphasic (cat@IL / scCO 2 ) systems is reported in this article. The e ﬃ cient immobilization of [Ru(CO)Cl(H)(PCy 3 ) 2 ] (1 mol%) in [EMPyr][NTf 2 ] and [BMIm][OTf] with the subsequent extraction of products with n -heptane permitted multiple reuses of the catalyst without a signiﬁcant decrease in its activity and stability (up to 7 runs). Utilization of scCO 2 as an extractant enabled a signiﬁcant reduction in the amount of catalyst leaching during the separation process, compared to extraction with n -heptane. Such e ﬃ cient catalyst immobilization allowed an intensiﬁcation of the processes in terms of its productivity, which was indicated by high cumulative TON values (up to 956) in contrast to the traditional approach of applying volatile organic solvents (TON = ~50–100). The reaction was versatile to styrenes with electron-donating and withdrawing substituents and vinylcyclohexane, generating unsaturated organoboron compounds, of which synthetic utility was shown by the direct transformation of extracted products in iododeborylation and Suzuki coupling processes. All synthesized compounds were characterized using 1 H, 13 C NMR and GC-MS, while leaching of the catalyst was detected with ICP-MS.


Introduction
Homogeneous catalysis has remained a key part of chemistry for several decades and is a powerful tool in the synthesis of valuable compounds. The high activity and selectivity of molecular catalysts under mild reaction conditions, the lack of diffusion barriers in comparison to heterogeneous systems, and the variability of their electronic and steric properties tuned by the proper design and choice of ligands and metal centers lead to their application in the chemical industry in the production of advanced polymers and fine chemicals [1,2]. On the other hand, homogeneous conditions generate notable problems in recovery and reuse of catalysts, which are mostly based on expensive noble transition metals (TM), for example, rhodium, iridium, platinum, palladium, or ruthenium. To obtain high TON values and the proper process selectivity, this precious catalyst is often sacrificed within the separation process. Moreover, homogeneous conditions require a considerable amount of volatile organic solvent to dissolve all reaction components: reagents and catalysts. Such an approach generates problems with the process economy resulting from the high solvent consumption within the process

Reaction and Extraction Conditions Screening
The studies were initiated by an investigation of the borylative coupling of vinylboronic acid pinacol ester (1) with styrene (2a) as a model reaction performed in several ILs based on pyrrolidinium ([EMPyr] + ) or 1-butyl-3-methylimidazolium ([BMIm] + ) cations and various inorganic and organic anions ( Figure 1). Most of them were successfully applied in TM-catalyzed transformations [16]. Borylative coupling is a catalytic reaction which occurs in the presence of Ru-H catalysts with the activation of the C-B bond in vinyl boronates and the C-H bond in olefins or O-H bond in alcohols, silanols or boronic acids furnishing boryl-substituted olefins, boronic esters, borasiloxanes or boroxanes respectively, with the simultaneous evolution of ethylene [29,[40][41][42][43]. For the initial ionic liquids screening, we applied slightly more rigorous reaction conditions if compared to the traditional approach of utilizing volatile organic solvents (a higher process temperature to ensure good homogeneity of the reaction mixture). [Ru(CO)Cl(H)(PCy3)2] was used as a catalyst, which was previously described as the most effective in this transformation. In all pyrrolidinium-based ionic liquids, a conversion of 1 was over 90% (Table 1, entry [1][2][3][4]. The complete conversion of 1 was observed only for [EMPyr][NTf2]. In general, a higher conversion of 1 was observed for pyrrolidinium cations with ethyl substituents. When butyl groups were attached to the pyrrolidinium cation, the product yield was slightly lower. Simultaneously, the application of trifluoromethanesulfonate anion ([OTf] − ) resulted in the lower conversion of substrates than for bis(trifluoromethylsulfonyl)imide anion ([NTf2] − ). Scheme 1. Ionic liquids-based recyclable protocols for the synthesis of unsaturated organoboron compounds.

Reaction and Extraction Conditions Screening
The studies were initiated by an investigation of the borylative coupling of vinylboronic acid pinacol ester (1) with styrene (2a) as a model reaction performed in several ILs based on pyrrolidinium ([EMPyr] + ) or 1-butyl-3-methylimidazolium ([BMIm] + ) cations and various inorganic and organic anions ( Figure 1). Most of them were successfully applied in TM-catalyzed transformations [16]. Borylative coupling is a catalytic reaction which occurs in the presence of Ru-H catalysts with the activation of the C-B bond in vinyl boronates and the C-H bond in olefins or O-H bond in alcohols, silanols or boronic acids furnishing boryl-substituted olefins, boronic esters, borasiloxanes or boroxanes respectively, with the simultaneous evolution of ethylene [29,[40][41][42][43].
Catalysts 2020, 10, x FOR PEER REVIEW 3 of 16 Scheme 1. Ionic liquids-based recyclable protocols for the synthesis of unsaturated organoboron compounds.

Reaction and Extraction Conditions Screening
The studies were initiated by an investigation of the borylative coupling of vinylboronic acid pinacol ester (1) with styrene (2a) as a model reaction performed in several ILs based on pyrrolidinium ([EMPyr] + ) or 1-butyl-3-methylimidazolium ([BMIm] + ) cations and various inorganic and organic anions ( Figure 1). Most of them were successfully applied in TM-catalyzed transformations [16]. Borylative coupling is a catalytic reaction which occurs in the presence of Ru-H catalysts with the activation of the C-B bond in vinyl boronates and the C-H bond in olefins or O-H bond in alcohols, silanols or boronic acids furnishing boryl-substituted olefins, boronic esters, borasiloxanes or boroxanes respectively, with the simultaneous evolution of ethylene [29,[40][41][42][43]. For the initial ionic liquids screening, we applied slightly more rigorous reaction conditions if compared to the traditional approach of utilizing volatile organic solvents (a higher process temperature to ensure good homogeneity of the reaction mixture). [Ru(CO)Cl(H)(PCy3)2] was used as a catalyst, which was previously described as the most effective in this transformation. In all pyrrolidinium-based ionic liquids, a conversion of 1 was over 90% (Table 1, entry [1][2][3][4]. The complete conversion of 1 was observed only for [EMPyr][NTf2]. In general, a higher conversion of 1 was observed for pyrrolidinium cations with ethyl substituents. When butyl groups were attached to the pyrrolidinium cation, the product yield was slightly lower. Simultaneously, the application of trifluoromethanesulfonate anion ([OTf] − ) resulted in the lower conversion of substrates than for bis(trifluoromethylsulfonyl)imide anion ([NTf2] − ). For the initial ionic liquids screening, we applied slightly more rigorous reaction conditions if compared to the traditional approach of utilizing volatile organic solvents (a higher process temperature to ensure good homogeneity of the reaction mixture). [Ru(CO)Cl(H)(PCy 3 ) 2 ] was used as a catalyst, which was previously described as the most effective in this transformation. In all pyrrolidinium-based ionic liquids, a conversion of 1 was over 90% (Table 1,   The presence of traces of water in those ILs probably caused partial deactivation of the moisture-sensitive catalyst. When [BMIm]Cl was used as a solvent and immobilization medium, no conversion of 1 was noticed. This can be explained by the strong coordination ability of chloride anion to the metal center of the catalyst, and inhibition of its activity. This observation is in agreement with previous reports [28,30]. [EMPyr][NTf 2 ] and [BMIm] [OTf], which ensured the complete conversion of 1 (Table 1, entry 2 and 6), were chosen for further reaction conditions screening. We optimized parameters crucial for obtaining the highest reaction yield, i.e., temperature, time, the molar ratio of substrates, as well as catalyst loading (Table 2). Initially, for [EMPyr][NTf 2 ], the high catalyst loading of [Ru(CO)Cl(H)(PCy 3 ) 2 ] (3 mol%) was maintained while the other parameters were tuned. The quantitative yields of 3a were observed above 110 • C. The same results were noticed when the time of the reaction was reduced from 24 to 6 h. Moreover, only a 1.5-fold excess of 2a towards 1 was necessary to get a full conversion of 1. In the final stage of optimization studies in [EMPyr][NTf 2 ], the influence of catalyst loading on reaction efficiency was determined. It was found that 1 mol% of [Ru(CO)Cl(H)(PCy 3 ) 2 ] is essential for achieving a very high reaction yield ( Table 2, entry 12). Although the application of the equimolar ratio of substrates resulted in a complete conversion of 1, the presence of a homocoupling product of 1 was observed ( Table 2, entry 14). Therefore, a small excess of olefin is essential for the elimination of the side-homocoupling reaction of vinyl boronate. Replacement of ruthenium hydride catalyst with coordinated PCy 3 ligand to [Ru(CO)Cl(H)(PPh 3 ) 3 ] leads to a lower conversion of 1 and the formation of undefined by-products (  16). It is worth emphasizing that the application of ILs as a solvent enhances reaction rate compared to an analogous reaction performed in poly (ethylene glycol), another green solvent with similar properties to ILs [29] The same phenomenon has already been observed by us during studies on the catalytic hydroboration of alkynes in Ru(CO)Cl(H)(PPh 3 ) 3 @ILs systems [30]. Among many possibilities for the separation of products from the homogeneous reaction mixture, extraction seems to be a fast and efficient method. The extractant should dissolve the reaction products well, not mix with an ionic liquid to prevent leaching of the catalyst, as well as not inhibiting or deactivating the catalyst. The right choice is crucial for the ability to reuse the catalytic system. To find the most appropriate medium for product extraction, we examined several organic solvents and scCO 2 (Table 3). Non-polar aliphatic hydrocarbons (n-hexane or n-heptane) are completely immiscible with [EMPyr][NTf 2 ] and [BMIm] [OTf], and during the extraction, the two phases were observed. The extractant (upper) phase was transparent or pale yellow. Application of more polar solvents such as toluene, dichloromethane or tetrahydrofuran resulted in partial or complete dissolution of the catalytic systems regardless of the ionic liquid used.  [OTf]. Additionally, it is known that scCO 2 is partially soluble in ILs, lowering their viscosity, while ILs are not soluble in this supercritical fluid. Therefore, such a biphasic system is suitable for carrying out the reaction/extraction process [44]. Based on extractant screening for further Catalysts 2020, 10, 762 6 of 15 experiments, n-heptane (lower neurotoxicity than n-hexane) and scCO 2 were chosen as solvents for product extraction from the post-reaction mixtures.

Scope of Substrates Investigations
Having optimized the reaction and extraction conditions in hand, we have studied a scope of olefins, mainly electron-deficient, neutral or donating styrenes, in borylative coupling with 1 in [BMIm][OTf] ( Table 4). The reaction of 1 with bromo-(2b) or fluoro-substitued (2c) styrenes in para position led to (E)-alkenyl boronates with high yields (Table 4, entry 2-3). Application of electron-withdrawing groups such as -CF 3 (2d-e) also gave an excellent conversion of 1. Trans-borylation of 1 with a weakly donating -CH 3 groups in meta (2f) or para (2g) positions resulted in the desired products 3f and 3g with very good isolation yields ( Table 4, entry 6-7). However, the utilization of the sterically hindered alkyl group -C(CH 3 ) 3 (2h) gave a lower conversion of 1. A similar result was noticeable when the electron-donating -OCH 3 group (2i) was applied. We also examined the reactivity of vinylcyclohexane (2j) in borylative coupling with 1. After 6 h, 3j was observed with a very high yield ( Table 4, entry 10).

Scope of Substrates Investigations
Having optimized the reaction and extraction conditions in hand, we have studied a scope of olefins, mainly electron-deficient, neutral or donating styrenes, in borylative coupling with 1 in [BMIm][OTf] ( Table 4). The reaction of 1 with bromo-(2b) or fluoro-substitued (2c) styrenes in para position led to (E)-alkenyl boronates with high yields (Table 4, entry 2-3). Application of electronwithdrawing groups such as -CF3 (2d-e) also gave an excellent conversion of 1. Trans-borylation of 1 with a weakly donating -CH3 groups in meta (2f) or para (2g) positions resulted in the desired products 3f and 3g with very good isolation yields ( Table 4, entry 6-7). However, the utilization of the sterically hindered alkyl group -C(CH3)3 (2h) gave a lower conversion of 1. A similar result was noticeable when the electron-donating -OCH3 group (2i) was applied. We also examined the reactivity of vinylcyclohexane (2j) in borylative coupling with 1. After 6 h, 3j was observed with a very high yield ( Table 4, entry 10).

Scope of Substrates Investigations
Having optimized the reaction and extraction conditions in hand, we have studied a scope of olefins, mainly electron-deficient, neutral or donating styrenes, in borylative coupling with 1 in [BMIm][OTf] ( Table 4). The reaction of 1 with bromo-(2b) or fluoro-substitued (2c) styrenes in para position led to (E)-alkenyl boronates with high yields (Table 4, entry 2-3). Application of electronwithdrawing groups such as -CF3 (2d-e) also gave an excellent conversion of 1. Trans-borylation of 1 with a weakly donating -CH3 groups in meta (2f) or para (2g) positions resulted in the desired products 3f and 3g with very good isolation yields ( Table 4, entry 6-7). However, the utilization of the sterically hindered alkyl group -C(CH3)3 (2h) gave a lower conversion of 1. A similar result was noticeable when the electron-donating -OCH3 group (2i) was applied. We also examined the reactivity of vinylcyclohexane (2j) in borylative coupling with 1. After 6 h, 3j was observed with a very high yield ( Table 4, entry 10).

Scope of Substrates Investigations
Having optimized the reaction and extraction conditions in hand, we have studied a scope of olefins, mainly electron-deficient, neutral or donating styrenes, in borylative coupling with 1 in [BMIm][OTf] ( Table 4). The reaction of 1 with bromo-(2b) or fluoro-substitued (2c) styrenes in para position led to (E)-alkenyl boronates with high yields (Table 4, entry 2-3). Application of electronwithdrawing groups such as -CF3 (2d-e) also gave an excellent conversion of 1. Trans-borylation of 1 with a weakly donating -CH3 groups in meta (2f) or para (2g) positions resulted in the desired products 3f and 3g with very good isolation yields ( Table 4, entry 6-7). However, the utilization of the sterically hindered alkyl group -C(CH3)3 (2h) gave a lower conversion of 1. A similar result was noticeable when the electron-donating -OCH3 group (2i) was applied. We also examined the reactivity of vinylcyclohexane (2j) in borylative coupling with 1. After 6 h, 3j was observed with a very high yield ( Table 4, entry 10).

Scope of Substrates Investigations
Having optimized the reaction and extraction conditions in hand, we have studied a scope of olefins, mainly electron-deficient, neutral or donating styrenes, in borylative coupling with 1 in Table 4). The reaction of 1 with bromo-(2b) or fluoro-substitued (2c) styrenes in para position led to (E)-alkenyl boronates with high yields (Table 4, entry 2-3). Application of electronwithdrawing groups such as -CF3 (2d-e) also gave an excellent conversion of 1. Trans-borylation of 1 with a weakly donating -CH3 groups in meta (2f) or para (2g) positions resulted in the desired products 3f and 3g with very good isolation yields ( Table 4, entry 6-7). However, the utilization of the sterically hindered alkyl group -C(CH3)3 (2h) gave a lower conversion of 1. A similar result was noticeable when the electron-donating -OCH3 group (2i) was applied. We also examined the reactivity of vinylcyclohexane (2j) in borylative coupling with 1. After 6 h, 3j was observed with a very high yield ( Table 4, entry 10).

Scope of Substrates Investigations
Having optimized the reaction and extraction conditions in hand, we have studied a scope of olefins, mainly electron-deficient, neutral or donating styrenes, in borylative coupling with 1 in Table 4). The reaction of 1 with bromo-(2b) or fluoro-substitued (2c) styrenes in para position led to (E)-alkenyl boronates with high yields (Table 4, entry 2-3). Application of electronwithdrawing groups such as -CF3 (2d-e) also gave an excellent conversion of 1. Trans-borylation of 1 with a weakly donating -CH3 groups in meta (2f) or para (2g) positions resulted in the desired products 3f and 3g with very good isolation yields ( Table 4, entry 6-7). However, the utilization of the sterically hindered alkyl group -C(CH3)3 (2h) gave a lower conversion of 1. A similar result was noticeable when the electron-donating -OCH3 group (2i) was applied. We also examined the reactivity of vinylcyclohexane (2j) in borylative coupling with 1. After 6 h, 3j was observed with a very high yield ( Table 4, entry 10).

Scope of Substrates Investigations
Having optimized the reaction and extraction conditions in hand, we have studied a scope of olefins, mainly electron-deficient, neutral or donating styrenes, in borylative coupling with 1 in Table 4). The reaction of 1 with bromo-(2b) or fluoro-substitued (2c) styrenes in para position led to (E)-alkenyl boronates with high yields (Table 4, entry 2-3). Application of electronwithdrawing groups such as -CF3 (2d-e) also gave an excellent conversion of 1. Trans-borylation of 1 with a weakly donating -CH3 groups in meta (2f) or para (2g) positions resulted in the desired products 3f and 3g with very good isolation yields ( Table 4, entry 6-7). However, the utilization of the sterically hindered alkyl group -C(CH3)3 (2h) gave a lower conversion of 1. A similar result was noticeable when the electron-donating -OCH3 group (2i) was applied. We also examined the reactivity of vinylcyclohexane (2j) in borylative coupling with 1. After 6 h, 3j was observed with a very high yield ( Table 4, entry 10).

Scope of Substrates Investigations
Having optimized the reaction and extraction conditions in hand, we have studied a scope of olefins, mainly electron-deficient, neutral or donating styrenes, in borylative coupling with 1 in Table 4). The reaction of 1 with bromo-(2b) or fluoro-substitued (2c) styrenes in para position led to (E)-alkenyl boronates with high yields (Table 4, entry 2-3). Application of electronwithdrawing groups such as -CF3 (2d-e) also gave an excellent conversion of 1. Trans-borylation of 1 with a weakly donating -CH3 groups in meta (2f) or para (2g) positions resulted in the desired products 3f and 3g with very good isolation yields ( Table 4, entry 6-7). However, the utilization of the sterically hindered alkyl group -C(CH3)3 (2h) gave a lower conversion of 1. A similar result was noticeable when the electron-donating -OCH3 group (2i) was applied. We also examined the reactivity of vinylcyclohexane (2j) in borylative coupling with 1. After 6 h, 3j was observed with a very high yield ( Table 4, entry 10).

Scope of Substrates Investigations
Having optimized the reaction and extraction conditions in hand, we have studied a scope of olefins, mainly electron-deficient, neutral or donating styrenes, in borylative coupling with 1 in Table 4). The reaction of 1 with bromo-(2b) or fluoro-substitued (2c) styrenes in para position led to (E)-alkenyl boronates with high yields (Table 4, entry 2-3). Application of electronwithdrawing groups such as -CF3 (2d-e) also gave an excellent conversion of 1. Trans-borylation of 1 with a weakly donating -CH3 groups in meta (2f) or para (2g) positions resulted in the desired products 3f and 3g with very good isolation yields ( Table 4, entry 6-7). However, the utilization of the sterically hindered alkyl group -C(CH3)3 (2h) gave a lower conversion of 1. A similar result was noticeable when the electron-donating -OCH3 group (2i) was applied. We also examined the reactivity of vinylcyclohexane (2j) in borylative coupling with 1. After 6 h, 3j was observed with a very high yield ( Table 4, entry 10).

Scope of Substrates Investigations
Having optimized the reaction and extraction conditions in hand, we have studied a scope of olefins, mainly electron-deficient, neutral or donating styrenes, in borylative coupling with 1 in Table 4). The reaction of 1 with bromo-(2b) or fluoro-substitued (2c) styrenes in para position led to (E)-alkenyl boronates with high yields (Table 4, entry 2-3). Application of electronwithdrawing groups such as -CF3 (2d-e) also gave an excellent conversion of 1. Trans-borylation of 1 with a weakly donating -CH3 groups in meta (2f) or para (2g) positions resulted in the desired products 3f and 3g with very good isolation yields ( Table 4, entry 6-7). However, the utilization of the sterically hindered alkyl group -C(CH3)3 (2h) gave a lower conversion of 1. A similar result was noticeable when the electron-donating -OCH3 group (2i) was applied. We also examined the reactivity of vinylcyclohexane (2j) in borylative coupling with 1. After 6 h, 3j was observed with a very high yield ( Table 4, entry 10).

Scope of Substrates Investigations
Having optimized the reaction and extraction conditions in hand, we have studied a scope of olefins, mainly electron-deficient, neutral or donating styrenes, in borylative coupling with 1 in Table 4). The reaction of 1 with bromo-(2b) or fluoro-substitued (2c) styrenes in para position led to (E)-alkenyl boronates with high yields (Table 4, entry 2-3). Application of electronwithdrawing groups such as -CF3 (2d-e) also gave an excellent conversion of 1. Trans-borylation of 1 with a weakly donating -CH3 groups in meta (2f) or para (2g) positions resulted in the desired products 3f and 3g with very good isolation yields ( Table 4, entry 6-7). However, the utilization of the sterically hindered alkyl group -C(CH3)3 (2h) gave a lower conversion of 1. A similar result was noticeable when the electron-donating -OCH3 group (2i) was applied. We also examined the reactivity of vinylcyclohexane (2j) in borylative coupling with 1. After 6 h, 3j was observed with a very high yield ( Table 4, entry 10).

Scope of Substrates Investigations
Having optimized the reaction and extraction conditions in hand, we have studied a scope of olefins, mainly electron-deficient, neutral or donating styrenes, in borylative coupling with 1 in Table 4). The reaction of 1 with bromo-(2b) or fluoro-substitued (2c) styrenes in para position led to (E)-alkenyl boronates with high yields (Table 4, entry 2-3). Application of electronwithdrawing groups such as -CF3 (2d-e) also gave an excellent conversion of 1. Trans-borylation of 1 with a weakly donating -CH3 groups in meta (2f) or para (2g) positions resulted in the desired products 3f and 3g with very good isolation yields ( Table 4, entry 6-7). However, the utilization of the sterically hindered alkyl group -C(CH3)3 (2h) gave a lower conversion of 1. A similar result was noticeable when the electron-donating -OCH3 group (2i) was applied. We also examined the reactivity of vinylcyclohexane (2j) in borylative coupling with 1. After 6 h, 3j was observed with a very high yield (Table 4, entry 10).

Scope of Substrates Investigations
Having optimized the reaction and extraction conditions in hand, we have studied a scope of olefins, mainly electron-deficient, neutral or donating styrenes, in borylative coupling with 1 in [BMIm][OTf] ( Table 4). The reaction of 1 with bromo-(2b) or fluoro-substitued (2c) styrenes in para position led to (E)-alkenyl boronates with high yields (Table 4, entry 2-3). Application of electronwithdrawing groups such as -CF3 (2d-e) also gave an excellent conversion of 1. Trans-borylation of 1 with a weakly donating -CH3 groups in meta (2f) or para (2g) positions resulted in the desired products 3f and 3g with very good isolation yields ( Table 4, entry 6-7). However, the utilization of the sterically hindered alkyl group -C(CH3)3 (2h) gave a lower conversion of 1. A similar result was noticeable when the electron-donating -OCH3 group (2i) was applied. We also examined the reactivity of vinylcyclohexane (2j) in borylative coupling with 1. After 6 h, 3j was observed with a very high yield (Table 4, entry 10).

Scope of Substrates Investigations
Having optimized the reaction and extraction conditions in hand, we have studied a scope of olefins, mainly electron-deficient, neutral or donating styrenes, in borylative coupling with 1 in [BMIm][OTf] ( Table 4). The reaction of 1 with bromo-(2b) or fluoro-substitued (2c) styrenes in para position led to (E)-alkenyl boronates with high yields (Table 4, entry 2-3). Application of electronwithdrawing groups such as -CF3 (2d-e) also gave an excellent conversion of 1. Trans-borylation of 1 with a weakly donating -CH3 groups in meta (2f) or para (2g) positions resulted in the desired products 3f and 3g with very good isolation yields ( Table 4, entry 6-7). However, the utilization of the sterically hindered alkyl group -C(CH3)3 (2h) gave a lower conversion of 1. A similar result was noticeable when the electron-donating -OCH3 group (2i) was applied. We also examined the reactivity of vinylcyclohexane (2j) in borylative coupling with 1. After 6 h, 3j was observed with a very high yield (Table 4, entry 10).

Scope of Substrates Investigations
Having optimized the reaction and extraction conditions in hand, we have studied a scope of olefins, mainly electron-deficient, neutral or donating styrenes, in borylative coupling with 1 in [BMIm][OTf] ( Table 4). The reaction of 1 with bromo-(2b) or fluoro-substitued (2c) styrenes in para position led to (E)-alkenyl boronates with high yields (Table 4, entry 2-3). Application of electronwithdrawing groups such as -CF3 (2d-e) also gave an excellent conversion of 1. Trans-borylation of 1 with a weakly donating -CH3 groups in meta (2f) or para (2g) positions resulted in the desired products 3f and 3g with very good isolation yields ( Table 4, entry 6-7). However, the utilization of the sterically hindered alkyl group -C(CH3)3 (2h) gave a lower conversion of 1. A similar result was noticeable when the electron-donating -OCH3 group (2i) was applied. We also examined the reactivity of vinylcyclohexane (2j) in borylative coupling with 1. After 6 h, 3j was observed with a very high yield (Table 4, entry 10).

Scope of Substrates Investigations
Having optimized the reaction and extraction conditions in hand, we have studied a scope of olefins, mainly electron-deficient, neutral or donating styrenes, in borylative coupling with 1 in [BMIm][OTf] ( Table 4). The reaction of 1 with bromo-(2b) or fluoro-substitued (2c) styrenes in para position led to (E)-alkenyl boronates with high yields (Table 4, entry 2-3). Application of electronwithdrawing groups such as -CF3 (2d-e) also gave an excellent conversion of 1. Trans-borylation of 1 with a weakly donating -CH3 groups in meta (2f) or para (2g) positions resulted in the desired products 3f and 3g with very good isolation yields ( Table 4, entry 6-7). However, the utilization of the sterically hindered alkyl group -C(CH3)3 (2h) gave a lower conversion of 1. A similar result was noticeable when the electron-donating -OCH3 group (2i) was applied. We also examined the reactivity of vinylcyclohexane (2j) in borylative coupling with 1. After 6 h, 3j was observed with a very high yield ( Table 4, entry 10).

Scope of Substrates Investigations
Having optimized the reaction and extraction conditions in hand, we have studied a scope of olefins, mainly electron-deficient, neutral or donating styrenes, in borylative coupling with 1 in [BMIm][OTf] ( Table 4). The reaction of 1 with bromo-(2b) or fluoro-substitued (2c) styrenes in para position led to (E)-alkenyl boronates with high yields (Table 4, entry 2-3). Application of electronwithdrawing groups such as -CF3 (2d-e) also gave an excellent conversion of 1. Trans-borylation of 1 with a weakly donating -CH3 groups in meta (2f) or para (2g) positions resulted in the desired products 3f and 3g with very good isolation yields ( Table 4, entry 6-7). However, the utilization of the sterically hindered alkyl group -C(CH3)3 (2h) gave a lower conversion of 1. A similar result was noticeable when the electron-donating -OCH3 group (2i) was applied. We also examined the reactivity of vinylcyclohexane (2j) in borylative coupling with 1. After 6 h, 3j was observed with a very high yield ( Table 4, entry 10).

Scope of Substrates Investigations
Having optimized the reaction and extraction conditions in hand, we have studied a scope of olefins, mainly electron-deficient, neutral or donating styrenes, in borylative coupling with 1 in [BMIm][OTf] ( Table 4). The reaction of 1 with bromo-(2b) or fluoro-substitued (2c) styrenes in para position led to (E)-alkenyl boronates with high yields (Table 4, entry 2-3). Application of electronwithdrawing groups such as -CF3 (2d-e) also gave an excellent conversion of 1. Trans-borylation of 1 with a weakly donating -CH3 groups in meta (2f) or para (2g) positions resulted in the desired products 3f and 3g with very good isolation yields ( Table 4, entry 6-7). However, the utilization of the sterically hindered alkyl group -C(CH3)3 (2h) gave a lower conversion of 1. A similar result was noticeable when the electron-donating -OCH3 group (2i) was applied. We also examined the reactivity of vinylcyclohexane (2j) in borylative coupling with 1. After 6 h, 3j was observed with a very high yield ( Table 4, entry 10).

Scope of Substrates Investigations
Having optimized the reaction and extraction conditions in hand, we have studied a scope of olefins, mainly electron-deficient, neutral or donating styrenes, in borylative coupling with 1 in [BMIm][OTf] ( Table 4). The reaction of 1 with bromo-(2b) or fluoro-substitued (2c) styrenes in para position led to (E)-alkenyl boronates with high yields (Table 4, entry 2-3). Application of electronwithdrawing groups such as -CF3 (2d-e) also gave an excellent conversion of 1. Trans-borylation of 1 with a weakly donating -CH3 groups in meta (2f) or para (2g) positions resulted in the desired products 3f and 3g with very good isolation yields ( Table 4, entry 6-7). However, the utilization of the sterically hindered alkyl group -C(CH3)3 (2h) gave a lower conversion of 1. A similar result was noticeable when the electron-donating -OCH3 group (2i) was applied. We also examined the reactivity of vinylcyclohexane (2j) in borylative coupling with 1. After 6 h, 3j was observed with a very high yield ( Table 4, entry 10).

Scope of Substrates Investigations
Having optimized the reaction and extraction conditions in hand, we have studied a scope of olefins, mainly electron-deficient, neutral or donating styrenes, in borylative coupling with 1 in [BMIm][OTf] ( Table 4). The reaction of 1 with bromo-(2b) or fluoro-substitued (2c) styrenes in para position led to (E)-alkenyl boronates with high yields (Table 4, entry 2-3). Application of electronwithdrawing groups such as -CF3 (2d-e) also gave an excellent conversion of 1. Trans-borylation of 1 with a weakly donating -CH3 groups in meta (2f) or para (2g) positions resulted in the desired products 3f and 3g with very good isolation yields ( Table 4, entry 6-7). However, the utilization of the sterically hindered alkyl group -C(CH3)3 (2h) gave a lower conversion of 1. A similar result was noticeable when the electron-donating -OCH3 group (2i) was applied. We also examined the reactivity of vinylcyclohexane (2j) in borylative coupling with 1. After 6 h, 3j was observed with a very high yield ( Table 4, entry 10).

Scope of Substrates Investigations
Having optimized the reaction and extraction conditions in hand, we have studied a scope of olefins, mainly electron-deficient, neutral or donating styrenes, in borylative coupling with 1 in [BMIm][OTf] ( Table 4). The reaction of 1 with bromo-(2b) or fluoro-substitued (2c) styrenes in para position led to (E)-alkenyl boronates with high yields (Table 4, entry 2-3). Application of electronwithdrawing groups such as -CF3 (2d-e) also gave an excellent conversion of 1. Trans-borylation of 1 with a weakly donating -CH3 groups in meta (2f) or para (2g) positions resulted in the desired products 3f and 3g with very good isolation yields ( Table 4, entry 6-7). However, the utilization of the sterically hindered alkyl group -C(CH3)3 (2h) gave a lower conversion of 1. A similar result was noticeable when the electron-donating -OCH3 group (2i) was applied. We also examined the reactivity of vinylcyclohexane (2j) in borylative coupling with 1. After 6 h, 3j was observed with a very high yield ( Table 4, entry 10).

Scope of Substrates Investigations
Having optimized the reaction and extraction conditions in hand, we have studied a scope of olefins, mainly electron-deficient, neutral or donating styrenes, in borylative coupling with 1 in [BMIm][OTf] ( Table 4). The reaction of 1 with bromo-(2b) or fluoro-substitued (2c) styrenes in para position led to (E)-alkenyl boronates with high yields (Table 4, entry 2-3). Application of electronwithdrawing groups such as -CF3 (2d-e) also gave an excellent conversion of 1. Trans-borylation of 1 with a weakly donating -CH3 groups in meta (2f) or para (2g) positions resulted in the desired products 3f and 3g with very good isolation yields ( Table 4, entry 6-7). However, the utilization of the sterically hindered alkyl group -C(CH3)3 (2h) gave a lower conversion of 1. A similar result was noticeable when the electron-donating -OCH3 group (2i) was applied. We also examined the reactivity of vinylcyclohexane (2j) in borylative coupling with 1. After 6 h, 3j was observed with a very high yield ( Table 4, entry 10). Simultaneously, the efficiency of extraction for different products of 3 was investigated. n-Heptane (3 × 5 mL at 60 • C) or scCO 2 (160-180 bar of CO 2 at 40 • C, 8 mL/min, 45 min) were applied as extractants. Very high extraction yields (over 90%) using n-heptane were obtained for most of the products (3a-f, 3j). Similar results were achieved for the product extraction with scCO 2 . It is worth noticing that when CO 2 -philic groups such as -F or -CF 3 were attached to the phenyl rings (3c-e), the extraction yields in scCO 2 were slightly higher (Table 4, entry 3-5). The extraction of product 3j with a cyclohexyl ring was almost quantitative due to its good affinity to both extractants.

Repetitive Batch Borylative Coupling in the Monophasic Solvent System-[Ru(CO)Cl(H)(PCy 3 ) 2 ]@ILs
A key objective of our research was to develop an efficient and more sustainable protocol for the synthesis of (E)-alkenyl boronates via borylative coupling of vinyl boronates with olefins in ILs. Having optimized the process (reaction and extraction) conditions, as well as the information on the reactivity of olefins (2a-j), we verified the possibility of catalytic system recycling after each run using  (Figure 2a,b) gave a final product 3a with very high yields up to the sixth run. For both ionic liquids, a gradual decrease in the reaction yield in the seventh up to the 10th cycle was observed. A higher extraction yield for extractant-soluble components (3a and excess or unreacted substrate) was noticed when n-heptane was used. Moreover, the cumulative turnover number (cTON) was several times higher than in the classical approach, utilizing volatile organic solvents (930-948 vs. approx. 50-100).

extraction.
Simultaneously, the efficiency of extraction for different products of 3 was investigated. n-Heptane (3 × 5 mL at 60 °C) or scCO2 (160-180 bar of CO2 at 40 °C, 8 mL/min, 45 min) were applied as extractants. Very high extraction yields (over 90%) using n-heptane were obtained for most of the products (3a-f, 3j). Similar results were achieved for the product extraction with scCO2. It is worth noticing that when CO2-philic groups such as -F or -CF3 were attached to the phenyl rings (3c-e), the extraction yields in scCO2 were slightly higher (Table 4, entry 3-5). The extraction of product 3j with a cyclohexyl ring was almost quantitative due to its good affinity to both extractants.

Repetitive Batch Borylative Coupling in the Monophasic Solvent System-[Ru(CO)Cl(H)(PCy3)2]@ILs
A key objective of our research was to develop an efficient and more sustainable protocol for the synthesis of (E)-alkenyl boronates via borylative coupling of vinyl boronates with olefins in ILs. Having optimized the process (reaction and extraction) conditions, as well as the information on the reactivity of olefins (2a-j), we verified the possibility of catalytic system recycling after each run using  (Figure 2a,b) gave a final product 3a with very high yields up to the sixth run. For both ionic liquids, a gradual decrease in the reaction yield in the seventh up to the 10th cycle was observed. A higher extraction yield for extractant-soluble components (3a and excess or unreacted substrate) was noticed when n-heptane was used. Moreover, the cumulative turnover number (cTON) was several times higher than in the classical approach, utilizing volatile organic solvents (930-948 vs. approx. 50-100).
Repetitive batch borylative coupling of 1 with 2d containing a CO2-phlilic trifluoromethyl group gave a very high product yield (over 90%) up to the seventh cycle for [BMIm][OTf] and [EMPyr][NTf2] (Figure 2c,d), respectively). The last three cycles resulted in a slight decrease in the reaction efficiency, but it was still at an acceptable level. Nevertheless, high values of cTON were obtained (941-956), showing good system activity.   (Figure 2c,d), respectively). The last three cycles resulted in a slight decrease in the reaction efficiency, Catalysts 2020, 10, 762 8 of 15 but it was still at an acceptable level. Nevertheless, high values of cTON were obtained (941-956), showing good system activity.
To investigate the possible cause of the gradual decrease in catalyst activity during the subsequent runs, extracts after the first, second, fifth and eighth runs were analyzed by inductively coupled plasma-mass spectrometry (ICP-MS). The highest ruthenium content was observed for extracts after the first and second runs (7.1-6.6 ppm) if n-heptane was applied regardless of the IL used. A pale yellow color was visible in both extracts. Although extracts analyzed after the fifth and eighth cycles were colorless, the ruthenium content was only a bit lower (6.4-4.8 ppm). Clearly better results were observed when scCO 2 was used as an extractant. For all ILs, ruthenium content in the analyzed extracts was comparable and lower than < 1 ppm. It should be pointed out that, despite significantly lower catalyst leaching in scCO 2 , the activity of catalytic systems was the same as for processes that used n-heptane for extraction. Thus, a gradual decrease in catalyst activity is rather caused by the formation of inactive catalyst species or non-coordinative cyclohexylphosphine oxide than catalyst leaching. To investigate the possible cause of the gradual decrease in catalyst activity during the subsequent runs, extracts after the first, second, fifth and eighth runs were analyzed by inductively coupled plasma-mass spectrometry (ICP-MS). The highest ruthenium content was observed for extracts after the first and second runs (7.1-6.6 ppm) if n-heptane was applied regardless of the IL used. A pale yellow color was visible in both extracts. Although extracts analyzed after the fifth and eighth cycles were colorless, the ruthenium content was only a bit lower (6.4-4.8 ppm). Clearly better results were observed when scCO2 was used as an extractant. For all ILs, ruthenium content in the analyzed extracts was comparable and lower than < 1 ppm. It should be pointed out that, despite significantly lower catalyst leaching in scCO2, the activity of catalytic systems was the same as for processes that used n-heptane for extraction. Thus, a gradual decrease in catalyst activity is rather caused by the formation of inactive catalyst species or non-coordinative cyclohexylphosphine oxide than catalyst leaching.

Repetitive Batch Borylative Coupling in the Biphasic Solvent System-[Ru(CO)Cl(H)(PCy3)2]@ILs/scCO2
In    At the end of our investigation on repetitive batch borylative coupling in the biphasic system, we verified the possibility of direct use of extracts in deborylation protocols, i.e., Suzuki coupling and iododeborylation (Scheme 2).

Scheme 2. Transformations of 3a via Suzuki coupling and iododeborylation reactions.
Suzuki coupling of 3a with bromobenzene in the presence of [Pd(PPh3)4] occurred with a complete conversion of 3a and with a very high isolation yield of (E)-1,2-diphenylethene (4) (87%). Similarly, iododeborylation of 3a with molecular iodine in the presence of sodium hydroxide resulted in a high isolation yield of (E)-(2-iodovinyl)benzene (5) (81%). The possibility of applying deborylation protocols with the use of crude extract is an attractive approach from the synthetical point of view because of the lack of necessity of carrying out time-and cost-consuming purification steps, for example, column chromatography or distillation.

General Procedures
All manipulations were performed under an argon atmosphere using standard Schlenk's techniques or in high-pressure autoclaves equipped with sapphire windows for the solubility tests of reagents and catalyst, when scCO 2 was used (For detailed analysis descriptions and NMR spectra of obtained products please see the Supplementary Materials).

Borylative Coupling in the [Ru(CO)Cl(H)(PCy 3 ) 2 ]@ILs/scCO 2 System with Subsequent scCO 2 Extraction
A high-pressure stainless steel autoclave reactor (10 mL) equipped with sapphire windows and connected to a Schlenk line, was charged with dried IL (1 g) and [Ru(CO)Cl(H)(PCy3)2] (0.01 mmol) in an argon atmosphere. Subsequently, vinylboronic acid pinacol ester (0.5 mmol) and olefin (0.75 mmol) were added and the reactor was pressurized with CO 2 to 55 bar, heated up to 110 • C and pressurized to the required pressure (approx. 170-190 bar). After 6 h, the reactor was cooled to 40 • C and the products were extracted in a CO 2 stream (160-180 bar of CO 2 , 8 mL/min, 45 min) into a small amount (10-15 mL) of n-heptane (previously cooled down in dry ice/i-propanol bath) to avoid product loss during extraction. Then the extracts were evaporated, weighed and characterized by GC-MS and 1 H NMR analyses.

Repetitive Batch Borylative Coupling in [Ru(CO)Cl(H)(PCy 3 ) 2 ]@ILs with Subsequent Organic Solvent Extraction
After the extraction process, the Schlenk's vessel was dried under vacuum for 20 min at 60 • C. Then a new portion of substrates was added in an argon atmosphere and subsequent batches, and extractions were carried out according to the procedure described in Section 3.2.1 without the isolation step.

Repetitive Batch Borylative Coupling in [Ru(CO)Cl(H)(PCy 3 ) 2 ]@ILs/scCO 2 with Subsequent scCO 2 Extraction
After the extraction process, the autoclave was dried in a vacuum for 20 min at 60 • C. Then a new portion of substrates was added in an argon atmosphere and subsequent batches, and extractions were carried out according to the procedure described in Section 3.2.2.

Suzuki Coupling of 3a with Bromobenzene
A 100 mL Schlenk vessel equipped with a stirring bar was charged with [Pd(PPh 3 ) 4 ] (5 mol%). Subsequently, THF (10 mL), 3a after scCO 2 extraction (0.5 mmol in 10 mL of n-heptane), bromobenzene (0.5 mmol) and 2 M aqueous solution of K 2 CO 3 (20 mL) were added. The reaction was carried out for 24 h at 50 • C. Then, the organic phase was separated, and the product was purified on silica by flash chromatography with a UV detector (λ 1 = 255 nm, λ 2 = 280 nm) using the purification conditions described in Section 3.2.1 in 87% yield. The product was characterized by GC-MS, 1 H and 13 C NMR analyses.

Iododeborylation of 3a with Molecular Iodine
To a 100 mL, round-bottom flask equipped with a stirring bar 3a after scCO 2 extraction, 10 mL of n-heptane and 5 mL of diethyl ether were added. Then 2 mL of the aqueous solution of NaOH (3 M) was dosed dropwise at 0 • C. Afterward, I 2 (0.85 mmol) in diethyl ether (5 mL) was slowly added. The reaction mixture was stirred for 2 h and then the excess of iodine was quenched with a saturated solution of sodium thiosulfate. The organic solution was separated, and the aqueous solution was washed with diethyl ether. The volatile organic fractions were evaporated, and the crude product was purified on silica by flash chromatography with a UV detector (λ 1 = 255 nm, λ 2 = 280 nm) using the purification conditions described in Section 3.2.1 in 81% yield. The product was characterized by GC-MS, 1 H and 13 C NMR analyses.  (19), 57 (14). Isolated yield: 78%. NMR and GC-MS data are in agreement with the literature [29].

Conclusions
The new, effective and highly regio-and stereoselective catalytic systems based on the immobilization of [Ru(CO)Cl(H)(PCy 3 ) 2 ] in ionic liquids for the borylative coupling of vinylboronic pinacol ester with olefins was presented for the first time within these studies. The best results, characterized by excellent product yields, were obtained when [BMIm][OTf] and [EMPyr][NTf 2 ] were used as solvents and catalyst immobilization media. The system permitted a transformation of various vinyl-substituted olefins (styrene (2a), functionalized styrenes (2b-i) and vinylcyclohexane (2j)) into useful borylsubstituted unsaturated products, which can be used in deborylation or Suzuki coupling reactions. The application of ILs permitted catalyst reuse and the carrying out of repetitive batch borylative coupling in monophasic [Ru(CO)Cl(H)(PCy 3 ) 2 ]@ILs or biphasic [Ru(CO)Cl(H)(PCy 3 ) 2 ]@[BMIm][OTf]/scCO 2 systems with product extraction with non-polar n-heptane or scCO 2 . These new protocols, under optimized reaction ([Ru-H]:1:2 = 0.01:1:1.5, 110 • C, 6 h, 1 g IL, inert atmosphere conditions) and extraction (3 × 5 mL of the n-heptane at 60 • C or 160-180 bar of CO 2 at 40 • C, 8 mL/min, 45 min) conditions, allowed of the catalyst to be reused 5-7 times without any significant loss of activity or stability. The application of scCO 2 as an extractant in monophasic or biphasic solvent systems significantly reduced catalyst leaching during the separation process (<1 ppm in each batch), compared to the extraction with n-heptane. Moreover, the good solubility of the reagents and products in scCO 2 and the high catalyst stability creates future possibilities for carrying out this process under a continuous flow method. In addition, it was found that the application of ILs as reaction media has a positive impact on the reaction rate, shortening the process from 24 h to 6 h. Such an approach based on multiple catalyst use enabled an intensification of the cumulative TON values (up to 956) in comparison to the single batch (~50-100), showing the potential of the system reported within this research, which was developed according to the sustainable development rules. The catalyst reuse, simplification of the separation process, increased process productivity and possibilities to carry out the reaction in repetitive batch borylative coupling of olefins are in agreement with green chemistry paradigms.