Grignard Reagent-Catalyzed Hydroboration of Esters, Nitriles, and Imines

The reduction in esters, nitriles, and imines requires harsh conditions (highly reactive reagents, high temperatures, and pressures) or complex metal-ligand catalytic systems. Catalysts comprising earth-abundant and less toxic elements are desirable from the perspective of green chemistry. In this study, we developed a green hydroboration protocol for the reduction in esters, nitriles, and imines at room temperature (25 °C) using pinacolborane as the reducing agent and a commercially available Grignard reagent as the catalyst. Screening of various alkyl magnesium halides revealed MeMgCl as the optimal catalyst for the reduction. The hydroboration and subsequent hydrolysis of various esters yielded corresponding alcohols over a short reaction time (~0.5 h). The hydroboration of nitriles and imines produced various primary and secondary amines in excellent yields. Chemoselective reduction and density functional theory calculations are also performed. The proposed green hydroboration protocol eliminates the requirements for complex ligand systems and elevated temperatures, providing an effective method for the reduction in esters, nitriles, and imines at room temperature.


Introduction
The reduction in esters to valuable functionalized alcohols, which are used as starting materials or solvents, is a common reaction in organic synthesis.These alcohols are typically used for synthesizing bioactive molecules and agrochemicals, as well as for further functional group transformations [1].However, owing to electronic and steric reasons, the transformation of esters into alcohols is relatively challenging compared with the corresponding reduction in aldehydes and ketones (i.e., aldehyde > ketone > ester).In particular, the conversion of esters to alcohols in the presence of other reducible groups requires additional steps.Highly reactive hydride reagents such as LiAlH 4 or LiBH 4 are commonly used for the conversion of esters to alcohols; however, these reactions afford low yields of alcohols and are not selective [2][3][4].In addition, the pressurized hydrogenation reaction requires high pressures and temperatures which limit functional group tolerance [5].To address these issues, catalyzed hydroelementation reactions, namely hydrosilylation and hydroboration reactions, have been developed using different catalytic systems, and the hydrosilylation of esters has previously been achieved [6][7][8][9][10][11][12].Hydroboration of esters using a mild reagent, namely pinacolborane (HBpin), as the reducing agent is convenient to handle and forms stable borylated intermediates [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28].
Similar to alcohols, amines are ubiquitous in natural compounds and are important building blocks in the synthesis of drugs, agrochemicals, coupling partners, dyes, and ligands for metal complexes [29][30][31].Hence, amine synthesis is of considerable interest to researchers in industry and academia.In this context, the reduction in nitriles and imines via hydroboration is a straightforward and convenient method to obtain amines in good yields [32][33][34][35][36][37].
In this context, we believe that a more economic and robust protocol without complex ligand systems is urgently required for the hydroboration of esters, nitriles, and imines.Grignard reagents are known to be effective synthetic partners for their tremendous applicability in numerous organic reactions, such as C-C cross coupling reactions to increase the carbon-carbon chain, and as alkylating reagents for carbonyl electrophiles etc. Ma et al. used Grignard reagents in the hydroboration of aldehydes and ketones and obtained good conversions [52].An et al. also observed good results for the hydroboration of esters and carbonyls using magnesium-based catalysts that are synthesized from Grignard reagents [53].Considering the findings of Rueping et al. [54,55] and Ma et al. [52], we aimed to identify the scope of readily available Mg reagents as catalysts in the reduction in C=O, C≡N, and C=N bonds (Figure 1).ligands for metal complexes [29][30][31].Hence, amine synthesis is of considerable interest to researchers in industry and academia.In this context, the reduction in nitriles and imines via hydroboration is a straightforward and convenient method to obtain amines in good yields [32][33][34][35][36][37].
In this context, we believe that a more economic and robust protocol without complex ligand systems is urgently required for the hydroboration of esters, nitriles, and imines.Grignard reagents are known to be effective synthetic partners for their tremendous applicability in numerous organic reactions, such as C-C cross coupling reactions to increase the carbon-carbon chain, and as alkylating reagents for carbonyl electrophiles etc. Ma et al. used Grignard reagents in the hydroboration of aldehydes and ketones and obtained good conversions [52].An et al. also observed good results for the hydroboration of esters and carbonyls using magnesium-based catalysts that are synthesized from Grignard reagents [53].Considering the findings of Rueping et al. [54,55] and Ma et al., [52] we aimed to identify the scope of readily available Mg reagents as catalysts in the reduction in C=O, C≡N, and C=N bonds (Figure 1).In this study, we developed Grignard reagent-catalyzed hydroboration protocols for esters, nitriles, and imines using HBpin at room temperature (25 °C).Subsequently, we investigated the Grignard reagent-catalyzed chemoselective hydroboration of esters in substrates comprising both esters and reducible groups such as nitriles, alkenes, and alkynes, and performed density functional theory (DFT) calculations to elucidate the mechanism of catalytic hydroboration (Scheme 1).In this study, we developed Grignard reagent-catalyzed hydroboration protocols for esters, nitriles, and imines using HBpin at room temperature (25 • C).Subsequently, we investigated the Grignard reagent-catalyzed chemoselective hydroboration of esters in substrates comprising both esters and reducible groups such as nitriles, alkenes, and alkynes, and performed density functional theory (DFT) calculations to elucidate the mechanism of catalytic hydroboration (Scheme 1).Scheme 1. Hydroboration of esters, nitriles, and imines using Grignard reagents.

Results and Discussion
Initially, the hydroboration of ethyl benzoate ester with HBpin was investigated using various alkyl magnesium halides at room temperature for 30 min.The ester hydroboration proceeded smoothly (99% conversion) with 5 mol% loading of methyl magnesium chloride and bromide catalysts (Table 1, entries 1 and 2).However, the conversion rate for methyl magnesium iodide was significantly lower than that of entry 1 (75%; Table 1, entry 3).In addition, n-butyl and tert-butyl magnesium chlorides provided >90% conversions (Table 1, entries 4 and 5), whereas iso-propyl and phenyl magnesium chlorides afforded 82% and 89% conversions, respectively (Table 1, entries 6 and 7).Hence, methyl magnesium chloride (MeMgCl) was selected for the further evaluation of reaction conditions.PhMgCl 89 a The conversion percentages were determined using gas chromatography based on the consumption of the starting material.
First, we determined a suitable solvent and catalyst concentration for the reaction (Tables S1 and S2).A 0.5 M MeMgCl solution prepared in dry THF afforded the highest conversion.Next, the catalyst loading and the amount of HBpin required for the reaction were optimized (Table 2).A decrease in the HBpin content from 2.5 to 2.0 equiv.decreased the conversion from 99% to 94% (entries 1-4).Similarly, a reduction in the catalyst loading by 1 mol% (i.e., to 4 and 3 mol%) led to an approximate 20% decrease in the conversion (entries 5 and 6).Therefore, the optimal conditions for the ester Scheme 1. Hydroboration of esters, nitriles, and imines using Grignard reagents.

Results and Discussion
Initially, the hydroboration of ethyl benzoate ester with HBpin was investigated using various alkyl magnesium halides at room temperature for 30 min.The ester hydroboration proceeded smoothly (99% conversion) with 5 mol% loading of methyl magnesium chloride and bromide catalysts (Table 1, entries 1 and 2).However, the conversion rate for methyl magnesium iodide was significantly lower than that of entry 1 (75%; Table 1, entry 3).In addition, n-butyl and tert-butyl magnesium chlorides provided >90% conversions (Table 1, entries 4 and 5), whereas iso-propyl and phenyl magnesium chlorides afforded 82% and 89% conversions, respectively (Table 1, entries 6 and 7).Hence, methyl magnesium chloride (MeMgCl) was selected for the further evaluation of reaction conditions.

Results and Discussion
Initially, the hydroboration of ethyl benzoate ester with HBpin was investigated using various alkyl magnesium halides at room temperature for 30 min.The ester hydroboration proceeded smoothly (99% conversion) with 5 mol% loading of methyl magnesium chloride and bromide catalysts (Table 1, entries 1 and 2).However, the conversion rate for methyl magnesium iodide was significantly lower than that of entry 1 (75%; Table 1, entry 3).In addition, n-butyl and tert-butyl magnesium chlorides provided >90% conversions (Table 1, entries 4 and 5), whereas iso-propyl and phenyl magnesium chlorides afforded 82% and 89% conversions, respectively (Table 1, entries 6 and 7).Hence, methyl magnesium chloride (MeMgCl) was selected for the further evaluation of reaction conditions.PhMgCl 89 a The conversion percentages were determined using gas chromatography based on the consumption of the starting material.
First, we determined a suitable solvent and catalyst concentration for the reaction (Tables S1 and S2).A 0.5 M MeMgCl solution prepared in dry THF afforded the highest conversion.Next, the catalyst loading and the amount of HBpin required for the reaction were optimized (Table 2).A decrease in the HBpin content from 2.5 to 2.0 equiv.decreased the conversion from 99% to 94% (entries 1-4).Similarly, a reduction in the catalyst loading by 1 mol% (i.e., to 4 and 3 mol%) led to an approximate 20% decrease in the conversion (entries 5 and 6).Therefore, the optimal conditions for the ester PhMgCl 89 a The conversion percentages were determined using gas chromatography based on the consumption of the starting material.
First, we determined a suitable solvent and catalyst concentration for the reaction (Tables S1 and S2).A 0.5 M MeMgCl solution prepared in dry THF afforded the highest conversion.Next, the catalyst loading and the amount of HBpin required for the reaction were optimized (Table 2).A decrease in the HBpin content from 2.5 to 2.0 equiv.decreased the conversion from 99% to 94% (entries 1-4).Similarly, a reduction in the catalyst loading by 1 mol% (i.e., to 4 and 3 mol%) led to an approximate 20% decrease in the conversion (entries 5 and 6).Therefore, the optimal conditions for the ester hydroboration reaction were 5 mol% catalyst loading (0.5 M in THF), 2.5 equiv. of HBpin, a reaction time of 30 min, and a reaction temperature of 25    a The conversion percentages were determined using gas chromatography based on the consumption of the starting material.
First, a suitable solvent and catalyst concentration were determined for the reaction (Tables S3 and S4).A 0.5 M MeMgCl solution in dry THF afforded the highest conversion.Hence, both the catalyst loading and amount of HBpin required for the reaction were optimized using the 0.5 M MeMgCl solution in dry THF.Three equivalents of HBpin and 3 mol% of catalyst afforded 97% conversion in 6 h (Table 5, entry 1).The conversion improved with increasing reaction time up to 12 h (entry 2), whereas it dramatically decreased when the catalyst loading was reduced to 2.0 mol% (entry 3).Moreover, 3 mol% of the catalyst and 2.5 equivalents of HBpin afforded a 99% conversion in 12 h (entry 4).In contrast, the conversion decreased when the catalyst loading was reduced to 2.0 mol% at the same reaction time (12 h, 83%, entry 5).However, the conversion increased to 99% with an increase in the reaction time (entry 6).The conversion slightly reduced upon decreasing the amount of HBpin from 2.5 to 2.2 equivalents (entry 7).Finally, the optimal conditions for nitrile hydroboration were 3 mol% catalyst loading (0.5 M in THF), 2.5 equiv. of HBpin, a reaction time of 12 h, and a reaction temperature of 25 °C (entry 4). a The conversion percentages were determined using gas chromatography based on the consumption of the starting material.
First, a suitable solvent and catalyst concentration were determined for the reaction (Tables S3 and S4).A 0.5 M MeMgCl solution in dry THF afforded the highest conversion.Hence, both the catalyst loading and amount of HBpin required for the reaction were optimized using the 0.5 M MeMgCl solution in dry THF.Three equivalents of HBpin and 3 mol% of catalyst afforded 97% conversion in 6 h (Table 5, entry 1).The conversion improved with increasing reaction time up to 12 h (entry 2), whereas it dramatically decreased when the catalyst loading was reduced to 2.0 mol% (entry 3).Moreover, 3 mol% of the catalyst and 2.5 equivalents of HBpin afforded a 99% conversion in 12 h (entry 4).In contrast, the conversion decreased when the catalyst loading was reduced to 2.0 mol% at the same reaction time (12 h, 83%, entry 5).However, the conversion increased to 99% with an increase in the reaction time (entry 6).The conversion slightly reduced upon decreasing the amount of HBpin from 2.5 to 2.2 equivalents (entry 7).Finally, the optimal conditions for nitrile hydroboration were 3 mol% catalyst loading (0.5 M in THF), 2.5 equiv. of HBpin, a reaction time of 12 h, and a reaction temperature of 25 • C (entry 4).  a The conversion percentages were determined using gas chromatography based on the consumption of the starting material.
First, a suitable solvent and catalyst concentration were determined for the reaction (Tables S3 and S4).A 0.5 M MeMgCl solution in dry THF afforded the highest conversion.Hence, both the catalyst loading and amount of HBpin required for the reaction were optimized using the 0.5 M MeMgCl solution in dry THF.Three equivalents of HBpin and 3 mol% of catalyst afforded 97% conversion in 6 h (Table 5, entry 1).The conversion improved with increasing reaction time up to 12 h (entry 2), whereas it dramatically decreased when the catalyst loading was reduced to 2.0 mol% (entry 3).Moreover, 3 mol% of the catalyst and 2.5 equivalents of HBpin afforded a 99% conversion in 12 h (entry 4).In contrast, the conversion decreased when the catalyst loading was reduced to 2.0 mol% at the same reaction time (12 h, 83%, entry 5).However, the conversion increased to 99% with an increase in the reaction time (entry 6).The conversion slightly reduced upon decreasing the amount of HBpin from 2.5 to 2.2 equivalents (entry 7).Finally, the optimal conditions for nitrile hydroboration were 3 mol% catalyst loading (0.5 M in THF), 2.5 equiv. of HBpin, a reaction time of 12 h, and a reaction temperature of 25 °C (entry 4). a The conversion percentages were determined using gas chromatography based on the consumption of the starting material.
In terms of the catalyst, methyl-and tert-butyl magnesium chlorides provided excellent conversions (99%, entries 1 and 6), whereas BuMgCl afforded 97% conversion (entry 5).In addition, MeMgBr and MeMgI afforded conversions of 91% and 78%, respectively (entries 2 and 3), iPrMgCl and PhMgCl afforded 83% conversions (entries 4 and 7).Subsequent investigations of the catalyst loading, HBpin content, and reaction time (Tables 7, S5 and S6) revealed the optimal conditions as 5 mol% MeMgCl, 1.5 equiv.HBpin, and a reaction time of 6 h.Although these conditions afforded the 99% The same method was then extended to imines.Even though imine hydroboration afforded good yields with the optimal conditions established for ester hydroboration, we further optimized the reaction conditions (Table 7).PhMgCl 83 a The conversion percentages were determined using gas chromatography based on the consumption of the starting material.
In terms of the catalyst, methyl-and tert-butyl magnesium chlorides provided excellent conversions (99%, entries 1 and 6), whereas BuMgCl afforded 97% conversion (entry 5).In addition, MeMgBr and MeMgI afforded conversions of 91% and 78%, respectively (entries 2 and 3), iPrMgCl and PhMgCl afforded 83% conversions (entries 4 and 7).Subsequent investigations of the catalyst loading, HBpin content, and reaction time (Tables 7, S5 and S6) revealed the optimal conditions as 5 mol% MeMgCl, 1.5 equiv.HBpin, and a reaction time of 6 h.Although these conditions afforded the 99% The same method was then extended to imines.Even though imine hydroboration afforded good yields with the optimal conditions established for ester hydroboration, we further optimized the reaction conditions (Table 7).PhMgCl 83 a The conversion percentages were determined using gas chromatography based on the consumption of the starting material.
The same method was then extended to imines.Even though imine hydroboration afforded good yields with the optimal conditions established for ester hydroboration, we further optimized the reaction conditions (Table 7).PhMgCl 83 a The conversion percentages were determined using gas chromatography based on the consumption of the starting material.
In terms of the catalyst, methyl-and tert-butyl magnesium chlorides provided excellent conversions (99%, entries 1 and 6), whereas BuMgCl afforded 97% conversion (entry 5).In addition, MeMgBr and MeMgI afforded conversions of 91% and 78%, respectively (entries 2 and 3), iPrMgCl and PhMgCl afforded 83% conversions (entries 4 and 7).Subsequent investigations of the catalyst loading, HBpin content, and reaction time (Tables 7, S5 and S6) revealed the optimal conditions as 5 mol% MeMgCl, 1.5 equiv.HBpin, and a reaction time of 6 h.Although these conditions afforded the 99% The same method was then extended to imines.Even though imine hydroboration afforded good yields with the optimal conditions established for ester hydroboration, we further optimized the reaction conditions (Table 7).PhMgCl 83 a The conversion percentages were determined using gas chromatography based on the consumption of the starting material.
In terms of the catalyst, methyl-and tert-butyl magnesium chlorides provided excellent conversions (99%, entries 1 and 6), whereas BuMgCl afforded 97% conversion (entry 5).In addition, MeMgBr and MeMgI afforded conversions of 91% and 78%, respectively (entries 2 and 3), iPrMgCl and PhMgCl afforded 83% conversions (entries 4 and 7).Subsequent investigations of the catalyst loading, HBpin content, and reaction time (Tables 7, S5 and S6) revealed the optimal conditions as 5 mol% MeMgCl, 1.5 equiv.HBpin, and a reaction time of 6 h.Although these conditions afforded the 99% The same method was then extended to imines.Even though imine hydroboration afforded good yields with the optimal conditions established for ester hydroboration, we further optimized the reaction conditions (Table 7).PhMgCl 83 a The conversion percentages were determined using gas chromatography based on the consumption of the starting material.
In terms of the catalyst, methyl-and tert-butyl magnesium chlorides provided excellent conversions (99%, entries 1 and 6), whereas BuMgCl afforded 97% conversion (entry 5).In addition, MeMgBr and MeMgI afforded conversions of 91% and 78%, respectively (entries 2 and 3), iPrMgCl and PhMgCl afforded 83% conversions (entries 4 and 7).Subsequent investigations of the catalyst loading, HBpin content, and reaction time (Tables 7, S5 and S6) revealed the optimal conditions as 5 mol% MeMgCl, 1.5 equiv.HBpin, and a reaction time of 6 h.Although these conditions afforded the 99% The same method was then extended to imines.Even though imine hydroboration afforded good yields with the optimal conditions established for ester hydroboration, we further optimized the reaction conditions (Table 7).PhMgCl 83 a The conversion percentages were determined using gas chromatography based on the consumption of the starting material.
The same method was then extended to imines.Even though imine hydroboration afforded good yields with the optimal conditions established for ester hydroboration, we further optimized the reaction conditions (Table 7).The same method was then extended to imines.Even though imine hydroboration afforded good yields with the optimal conditions established for ester hydroboration, we further optimized the reaction conditions (Table 7).PhMgCl 83 a The conversion percentages were determined using gas chromatography based on the consumption of the starting material.
In terms of the catalyst, methyl-and tert-butyl magnesium chlorides provided excellent conversions (99%, entries 1 and 6), whereas BuMgCl afforded 97% conversion (entry 5).In addition, MeMgBr and MeMgI afforded conversions of 91% and 78%, respectively (entries 2 and 3), iPrMgCl and PhMgCl afforded 83% conversions (entries 4 and 7).Subsequent investigations of the catalyst loading, HBpin content, and reaction time (Tables 7, S5 and S6) revealed the optimal conditions as 5 mol% MeMgCl, 1.5 equiv.HBpin, and a reaction time of 6 h.Although these conditions afforded the 99% PhMgCl 83 a The conversion percentages were determined using gas chromatography based on the consumption of the starting material.
In terms of the catalyst, methyl-and tert-butyl magnesium chlorides provided excellent conversions (99%, entries 1 and 6), whereas BuMgCl afforded 97% conversion (entry 5).In addition, MeMgBr and MeMgI afforded conversions of 91% and 78%, respectively (entries 2 and 3), iPrMgCl and PhMgCl afforded 83% conversions (entries 4 and 7).Subsequent investigations of the catalyst loading, HBpin content, and reaction time (Table 7, Tables S5 and S6) revealed the optimal conditions as 5 mol% MeMgCl, 1.5 equiv.HBpin, and a reaction time of 6 h.Although these conditions afforded the 99% conversion, the conversion was considerably reduced upon decreasing the catalyst loading and reaction time.
Table 9.Substrate scope of the imine hydroboration a .
Table 9.Substrate scope of the imine hydroboration a .
Table 9.Substrate scope of the imine hydroboration a .
Table 9.Substrate scope of the imine hydroboration a .
Finally, the efficiency of the catalyst was investigated using chemoselective hydroboration.Intramolecular chemoselective hydroboration was performed using esters containing other reducible functional groups, nitriles, alkenes, and alkynes.The ester group was selectively reduced to afford the corresponding alcohols in good yields (Scheme 2).
Finally, the efficiency of the catalyst was investigated using chemoselective hydroboration.Intramolecular chemoselective hydroboration was performed using esters containing other reducible functional groups, nitriles, alkenes, and alkynes.The ester group was selectively reduced to afford the corresponding alcohols in good yields (Scheme 2).
Finally, the efficiency of the catalyst was investigated using chemoselective hydroboration.Intramolecular chemoselective hydroboration was performed using esters containing other reducible functional groups, nitriles, alkenes, and alkynes.The ester group was selectively reduced to afford the corresponding alcohols in good yields (Scheme 2).
Finally, the efficiency of the catalyst was investigated using chemoselective hydroboration.Intramolecular chemoselective hydroboration was performed using esters containing other reducible functional groups, nitriles, alkenes, and alkynes.The ester group was selectively reduced to afford the corresponding alcohols in good yields (Scheme 2).
Finally, the efficiency of the catalyst was investigated using chemoselective hydroboration.Intramolecular chemoselective hydroboration was performed using esters containing other reducible functional groups, nitriles, alkenes, and alkynes.The ester group was selectively reduced to afford the corresponding alcohols in good yields (Scheme 2).
Finally, the efficiency of the catalyst was investigated using chemoselective hydroboration.Intramolecular chemoselective hydroboration was performed using esters containing other reducible functional groups, nitriles, alkenes, and alkynes.The ester group was selectively reduced to afford the corresponding alcohols in good yields (Scheme 2).
Finally, the efficiency of the catalyst was investigated using chemoselective hydroboration.Intramolecular chemoselective hydroboration was performed using esters containing other reducible functional groups, nitriles, alkenes, and alkynes.The ester group was selectively reduced to afford the corresponding alcohols in good yields (Scheme 2).
Finally, the efficiency of the catalyst was investigated using chemoselective hydroboration.Intramolecular chemoselective hydroboration was performed using esters containing other reducible functional groups, nitriles, alkenes, and alkynes.The ester group was selectively reduced to afford the corresponding alcohols in good yields (Scheme 2).The reaction pathway for MeMgCl-catalyzed hydroboration of benzoate was investigated using DFT calculations at the M06-2X/6-31G(d,p) level of theory [56].A schematic of the free energy profile for the reaction pathway is shown in Scheme 3. The reaction is divided into two catalytic cycles.The initial step is an exergonic reaction (-14.5The reaction pathway for MeMgCl-catalyzed hydroboration of benzoate was investigated using DFT calculations at the M06-2X/6-31G(d,p) level of theory [56].A schematic of the free energy profile for the reaction pathway is shown in Scheme 3. The reaction is divided into two catalytic cycles.The initial step is an exergonic reaction (−14.

General Information
All glassware used was dried thoroughly in an oven, assembled hot, and cooled under a stream of dry nitrogen prior to use.All reactions and manipulations of air-and moisture-sensitive materials were carried out using standard techniques for the handling of such materials.All chemicals were commercial products of the highest purity which were further purified before use by using standard methods.HBpin, aldehydes, ketones, and alkenes were purchased from Aldrich Chemical Company, Alfa Aesar, and Tokyo Chemical Industry Company (TCI). 1 H NMR spectra were measured at 400 MHz with CDCl 3 as a solvent at ambient temperature unless otherwise indicated and the chemical shifts were recorded in parts per million downfield from tetramethylsilane (δ = 0 ppm) or based on residual CDCl 3 (δ = 7.26 ppm) as the internal standard.The coupling constants (J) are reported in hertz.Analytical thin-layer chromatography (TLC) was performed on glass precoated with silica gel (Merck, Rahway, NJ, USA, silica gel 60 F 254 ).Column chromatography was carried out using 70-230 mesh silica gel (Merck) at normal pressure.GC analyses were performed on a Younglin Acme 6100M and 6500 GC FID chromatography, using an HP-5 capillary column (30 m).All GC yields were determined with the use of naphthalene as the internal standard and the authentic sample.

Catalytic Hydroboration of Ester
A 10 mL test tube was charged with a magnet, closed with septum, and flushed with argon.To this, 0.0751 g (1.0 eq) of ethyl benzoate, 0.18 mL (2.5 eq) of pinacolborane, and 0.05 mL (5 mol%) of 0.5 M methyl magnesium chloride were added at room temperature.
Contents were stirred for the given time (mentioned in Table 3) at the same temperature.After completion of the reaction (analyzed by GC), the reaction was terminated by the addition of water (1 mL).The crude mixture was hydrolyzed to alcohol by adding 1 N aqueous NaOH solution (1 mL).The resulting mixture was extracted with diethyl ether, washed with brine, and the combined organic layers were dried over MgSO 4 .After filtration, the solvents were evaporated under reduced pressure and the mixed residue was purified by silica gel column chromatography.

Catalytic Hydroboration of Nitrile
A 10 mL test tube was charged with a magnet, closed with septum, and flushed with argon.To this, 0.0515 g (1.0 eq) of benzonitrile, 0.18 mL (2.5 eq) of pinacolborane, and 0.03 mL (3 mol%) of 0.5 M methyl magnesium chloride were added at room temperature.The contents were stirred for 12 h at the same temperature.After completion of the reaction (analyzed by GC), the solvents were evaporated under reduced pressure.The crude mixture was analyzed by NMR using 1,3,5-trimethoxybenzene as an internal standard.

Catalytic Hydroboration of Imine
A 10 mL test tube was charged with a magnet, closed with septum, and flushed with argon.To this, 0.0906 g (1.0 eq) of benzylideneaniline, 0.11 mL (1.5 eq) of pinacolborane, and 0.05 mL (5 mol%) of 0.5 M methyl magnesium chloride were added at room temperature.The contents were stirred for 6 h at the same temperature.After completion of the reaction (analyzed by GC), the reaction was terminated by the addition of water (1 mL).The crude mixture was extracted with ethyl acetate and the combined organic layers were dried over MgSO 4 .After filtration, the solvents were evaporated under reduced pressure and the mixed residue was purified by silica gel column chromatography.

a
Isolated yields after silica column chromatography.b Yields were calculated by1 H NMR with 1,3,5-trimethoxybenzene as the internal standard.

a
Isolated yields after silica column chromatography.b Yields were calculated by1 H NMR with 1,3,5-trimethoxybenzene as the internal standard.

a
Isolated yields after silica column chromatography.b Yields were calculated by1 H NMR with 1,3,5-trimethoxybenzene as the internal standard.

a
Isolated yields after silica column chromatography.b Yields were calculated by1 H NMR with 1,3,5-trimethoxybenzene as the internal standard.

a
Isolated yields after silica column chromatography.b Yields were calculated by1 H NMR with 1,3,5-trimethoxybenzene as the internal standard.

a
Isolated yields after silica column chromatography.b Yields were calculated by1 H NMR with 1,3,5-trimethoxybenzene as the internal standard.

a
Isolated yields after silica column chromatography.b Yields were calculated by1 H NMR with 1,3,5-trimethoxybenzene as the internal standard.

a
Isolated yields after silica column chromatography.b Yields were calculated by1 H NMR with 1,3,5-trimethoxybenzene as the internal standard.

a
Isolated yields after silica column chromatography.b Yields were calculated by1 H NMR with 1,3,5-trimethoxybenzene as the internal standard.

a
Isolated yields after silica column chromatography.b Yields were calculated by1 H NMR with 1,3,5-trimethoxybenzene as the internal standard.

a
Isolated yields after silica column chromatography.b Yields were calculated by1 H NMR with 1,3,5-trimethoxybenzene as the internal standard.

a
Isolated yields after silica column chromatography.b Yields were calculated by1 H NMR with 1,3,5-trimethoxybenzene as the internal standard.

a
Isolated yields after silica column chromatography.b Yields were calculated by1 H NMR with 1,3,5-trimethoxybenzene as the internal standard.

a
Isolated yields after silica column chromatography.b Yields were calculated by1 H NMR with 1,3,5-trimethoxybenzene as the internal standard.

a
Isolated yields after silica column chromatography.b Yields were calculated by1 H NMR with 1,3,5-trimethoxybenzene as the internal standard.

a
Isolated yields after silica column chromatography.b Yields were calculated by1 H NMR with 1,3,5-trimethoxybenzene as the internal standard.

a
Isolated yields after silica column chromatography.b Yields were calculated by1 H NMR with 1,3,5-trimethoxybenzene as the internal standard.

a
Isolated yields after silica column chromatography.b Yields were calculated by1 H NMR with 1,3,5-trimethoxybenzene as the internal standard.

Scheme 4 .
Scheme 4. Plausible mechanism for the ester hydroboration in the presence of a Grignard reagent catalyst (MeMgCl) and the hydroboration reagent (HBpin) based on the free energy profile shown in Scheme 3.

Table 1 .
Hydroboration of ester using various alkyl magnesium halides.

Table 1 .
Hydroboration of ester using various alkyl magnesium halides.

Table 1 .
Hydroboration of ester using various alkyl magnesium halides.

Table 2 .
Optimization of the pinacolborane (HBpin) content and the catalyst (0.5 M MeMgCl in THF) loading for the ester hydroboration.

Table 2 .
Optimization of the pinacolborane (HBpin) content and the catalyst (0.5 M MeMgCl in THF) loading for the ester hydroboration.

Table 2 .
Optimization of the pinacolborane (HBpin) content and the catalyst (0.5 M MeMgCl in THF) loading for the ester hydroboration.

Table 6 .
Substrate scope of the nitrile hydroboration a .

Table 6 .
Substrate scope of the nitrile hydroboration a . .

Table 6 .
Substrate scope of the nitrile hydroboration a . .

Table 6 .
Substrate scope of the nitrile hydroboration a . .

Table 6 .
Substrate scope of the nitrile hydroboration a . .

Table 6 .
Substrate scope of the nitrile hydroboration a . .

Table 6 .
Substrate scope of the nitrile hydroboration a . .

Table 6 .
Substrate scope of the nitrile hydroboration a . .

Table 6 .
Substrate scope of the nitrile hydroboration a . .

Table 6 .
Substrate scope of the nitrile hydroboration a . .

Table 6 .
Substrate scope of the nitrile hydroboration a . .

Table 6 .
Substrate scope of the nitrile hydroboration a . .

Table 6 .
Substrate scope of the nitrile hydroboration a . .

Table 6 .
Substrate scope of the nitrile hydroboration a . .

Table 9 .
Substrate scope of the imine hydroboration a .

Table 9 .
Substrate scope of the imine hydroboration a .