Selective Manganese-Catalyzed Semihydrogenation of Alkynes with in-situ Generated H2 from KBH4 and Methanol

The selective semihydrogenation of alkynes with the Mn(I) alkyl catalyst fac[Mn(dippe)(CO)3(CH2CH2CH3)] (dippe = 1,2-bis(di-iso-propylphosphino)ethane) as pre-catalyst is described. Hydrogen gas required for the hydrogenation is generated in situ upon alcoholysis of KBH4 with methanol. A series of aryl-aryl, aryl-alkyl, alkyl-alkyl and terminal alkynes were readily hydrogenated to yield E-alkenes in good to excellent isolated yields. The reaction proceeds at 90°C with catalyst loadings of 0.5 -2 mol%. The implemented protocol tolerates a variety of electron donating and electron withdrawing functional groups including halides, phenols, nitriles, unprotected amines and heterocycles. The reaction can be upscaled to the gram scale. Mechanistic investigations including deuterium labelling studies and DFT calculations were undertaken to provide a reasonable reaction mechanism showing that initially formed Z-isomer undergoes fast isomerization to afford the thermodynamically more stable E-isomer. INTRODUCTION The selective semihydrogenation of alkynes plays a crucial role in bulk industry, fine chemistry and chemical research.1 Examples of relevant applications are found in the hydrocarbon refinery for petrol industry,1c, 1e, 2 the commercial synthetic routes for Resveratrol or Vitamin A.1a Thus far, traditional systems for the selective formation of Z-, Eor terminal alkenes consist of Pd/C,3 Lindlar catalyst,4 Birch reduction,5 Raney-Nickel6 or Wilkinson catalyst.7 Due to limitations regarding selectivity, activity, amount of produced waste or catalyst price, the study and improvement of these protocols has attracted numerous research groups in academia and industry.1a, 1b, 8 Thus, high activity and excellent selectivity-tailoring is being achieved by combining fine-tuned ligands with noble metals such as Ru,9 Rh,10 Pd11 and Ir.12 During the last decade, the concerns in regard to Green chemistry principles have been grown rapidly13 and the development of catalysts based on earth-abundant metals for organic transformations has become of very important.14 In recent years, several reports on selective alkyne semihydrogenations using catalysts based on Cr,15 Mn,16 Fe,17 Co,18 Ni,19 Cu20 are described. As manganese is concerned, the use of pincer-type ligands and bifunctional catalysis21 is crucial in the field of semi(transfer)hydrogenation of alkynes (Scheme 1, MnI – MnV). However, high selectivity towards E-alkenes and the conversion of alkyl-alkyl substituted alkynes or terminal alkynes with high functional group tolerance remains challenging.1a In addition, alcohols are potential coordinating ligands towards organometallic complexes which may have limited the use of more environmentally friendly and potentially bio-accessible alcohols as media for nonprecious metal based systems. Therefore, reports of selective semihydrogenations of alkynes are rare.16b, 18d, 19d, 20a We have recently reported on the application of the Mn(I) alkyl complex fac-[Mn(dippe)(CO)3(CH2CH2CH3)] (dippe = 1,2-bis(di-iso-propylphosphino)ethane) (Mn1) as pre-catalysts for the hydrogenation of ketones,22 nitriles23 and alkenes,24 CO2, the boration and diboration of alkenes and alkynes,26 the dehydrogenative silylation of alkenes27 and the dimerization and cross coupling of terminal alkynes.28 Inspired by these results we wondered if Mn1 is also active in the semihydrogenation of alkynes. Herein, we report on the use of Mn1 as pre-catalysts for the E-selective semihydrogenation of internal alkynes and the conversion of terminal alkynes in MeOH as solvent in the presence of KBH4. We take advantage of the fact that the BH4 anion undergoes fast alcoholysis to generate in situ hydrogen gas29 which is required for the hydrogenation of alkynes without the need of high-pressure equipment


INTRODUCTION
The selective semihydrogenation of alkynes plays a crucial role in bulk industry, fine chemistry and chemical research. 1 Examples of relevant applications are found in the hydrocarbon refinery for petrol industry, 1c, 1e, 2 the commercial synthetic routes for Resveratrol or Vitamin A. 1a Thus far, traditional systems for the selective formation of Z-, Eor terminal alkenes consist of Pd/C, 3 Lindlar catalyst, 4 Birch reduction, 5 Raney-Nickel 6 or Wilkinson catalyst. 7 Due to limitations regarding selectivity, activity, amount of produced waste or catalyst price, the study and improvement of these protocols has attracted numerous research groups in academia and industry. 1a, 1b, 8 Thus, high activity and excellent selectivity-tailoring is being achieved by combining fine-tuned ligands with noble metals such as Ru, 9 Rh, 10 Pd 11 and Ir. 12 During the last decade, the concerns in regard to Green chemistry principles have been grown rapidly 13 and the development of catalysts based on earth-abundant metals for organic transformations has become of very important. 14 In recent years, several reports on selective alkyne semihydrogenations using catalysts based on Cr, 15 Mn, 16 Fe, 17 Co, 18 Ni, 19 Cu 20 are described.
As manganese is concerned, the use of pincer-type ligands and bifunctional catalysis 21 is crucial in the field of semi-(transfer)hydrogenation of alkynes (Scheme 1, MnI -MnV). However, high selectivity towards E-alkenes and the conversion of alkyl-alkyl substituted alkynes or terminal alkynes with high functional group tolerance remains challenging. 1a In addition, alcohols are potential coordinating ligands towards organometallic complexes which may have limited the use of more environmentally friendly and potentially bio-accessible alcohols as media for nonprecious metal based systems. Therefore, reports of selective semihydrogenations of alkynes are rare. 16b, 18d, 19d, 20a We have recently reported on the application of the Mn(I) alkyl complex fac-[Mn(dippe)(CO)3(CH2CH2CH3)] (dippe = 1,2-bis(di-iso-propylphosphino)ethane) (Mn1) as pre-catalysts for the hydrogenation of ketones, 22 nitriles 23 and alkenes, 24 CO2, 25 the boration and diboration of alkenes and alkynes, 26 the dehydrogenative silylation of alkenes 27 and the dimerization and cross coupling of terminal alkynes. 28 Inspired by these results we wondered if Mn1 is also active in the semihydrogenation of alkynes. Herein, we report on the use of Mn1 as pre-catalysts for the E-selective semihydrogenation of internal alkynes and the conversion of terminal alkynes in MeOH as solvent in the presence of KBH4. We take advantage of the fact that the BH4anion undergoes fast alcoholysis to generate in situ hydrogen gas 29 which is required for the hydrogenation of alkynes without the need of high-pressure equipment such as autoclaves.
Scheme 1. Overview of Manganese-based Catalysts for the Semihydrogenation Alkynes.

RESULTS AND DISCUSSION
In order to establish the best reaction conditions for the semi-hydrogenation of alkynes, diphenyl acetylene (1a) was chosen as model substrate in combination with MeOH and KBH4 as hydrogen source. When 1a was treated with 1 mol % of Mn1 at 60°C with MeOH and 0.5 equiv of KBH4, E-stilbene (1b) was obtained in 99% isolated yield (Table 1, entry 1). Only traces of Z-stilbene (1c) were observed and over-hydrogenation did not take place.
Encouraged by this finding, temperature, catalyst loading and H2 sources were screened (Table 1). With catalyst loadings of 1.0 and 0.5 mol% an almost quantitative formation of 1b was achieved (  [5][6]. The performance of MeOH was compared to EtOH and iPrOH leading to lower yields (Table 1, entries 7-8). It is worth mentioning that the typical by-products from dehydrogenation of EtOH and iPrOH such as AcOEt and acetone were not observed and, thus, a transfer hydrogenation process can be ruled out. Instead, the corresponding signals of [B(OMe)4]as a result of alcoholysis of KBH4 with MeOH were detected by 11 B NMR spectroscopy (see SI,Figures S4 and 5). 29 For comparison, when the reaction was performed in the presence of H2 (30 bar) in MeOH and toluene, respectively, E-stilbene (1b) was obtained in 13 and 99 % yields (Table 1, entries 9 and 10). Accordingly, in-situ formation of H2 from alcoholysis of the BH4anion plays the key role in this hydrogenation. Addition of water resulted in no significant change in conversion and selectivity (Table 1, entry 11). In the absence of catalyst, no reaction takes place (Table 1, entry 12). GC monitoring of the reaction revealed full consumption of 1a within 3 h (a kinetic profile is provided in the SI, Figure S1). Upon reaction progress, 1c was detected as intermediate (ca 10%) which rapidly isomerizes to the corresponding E-alkene (1b). There was no evidence of overreduction to afford the corresponding alkane after 20 h. Encouraged by the high activity of the semihydrogenation of 1a, a series of aryl-aryl substituted alkynes were investigated as substrates (Table 2). It turned out that in order to achieve high yields and good E/Z rations, for substrates other than 1a the catalyst loadings had to be increased from 0.5 to 1 or 2 mol% in the case of terminal alkynes (vide infra). Likewise, when the reactions were performed at 90 o C significantly higher yields and E/Z ratios could be achieved.
Under these conditions, ortho-, metaand para-alkyl substituted alkynes gave full conversion to E-stilbenes with excellent selectivity ( Table 2, 1b-5b). In the case of 1-methyl-2-(phenylethynyl)benzene (3a)and 1-ethyl-4-((4hexylphenyl)ethynyl)benzene (4a) the catalyst loading had to be increased to 2 mol% to afford the desired Ealkenes in high isolated yields of 99 and 89%, respectively ( In the next step, aryl-alkyl substituted alkynes were investigated. These substrates tend to be more challenging in selective semihydrogenation due to over reduction and isomerization. Under the given reaction conditions nonactivated aryl-alkyl alkynes bearing several alkyl group substituents afforded corresponding E-styrene derivatives in good to excellent yields ( Table 2, 20b-24b). For instance, 20a gave the desired alkene with a E/Z ratio of 86:14 in 78% yield together with only 3 % over-hydrogenated product ( Table 2, 20b). In the case of the sterically hindered 1-tbutyl-2-phenylacetylene (25a) as well as the conjugated diyne 26a only traces of product were detected ( Table  2, 25b, 26b).

Scheme 2. Selective Hydrogenation of 1a and Isomerization of Z-Stilbene (1c) to E-Stilbene (1b) Catalyzed by Mn1.
It has to be mentioned that the removal of alkyne impurities in the presence of olefins via alkyne semihydrogenation is of interest for industrial purposes since it benefits the subsequent polymerizations of some light hydrocarbon fractions from steam cracking. 2 Due to the high selectivity of the introduced protocol, we investigated the potential applicability of this system for the purification of olefins. Accordingly, treating a mixture of 1a and 1c (1:100) with Mn1 (0.5 mol%) in the presence of KBH4 in MeOH resulted in full conversion of the mixture to Estilbene (1b) without formation of over-hydrogenated product 1d (Scheme 2).
Alkyl-alkyl substituted alkynes tend to be a challenging class of substrates in the field of semihydrogenation. Selective semihydrogenation of these substrates using manganese catalyst is rare and so far limited to dodecyne (28a) in up to 67% yield. 16d, 16e Interestingly, Mn1 was proven to be highly active also for the transformation of alkylalkyl substrates alkenes with moderate selectivity as depicted in Table 3. Over-hydrogenation was observed for some substrates. For instance, 4-octyne (27a) yielded 80% yield of desired product with an E/Z ratio of 2:1 ratio together with 20% of over-hydrogenated product ( Table 3, 27b). On the other hand, alkynes with longer aliphatic chains proved to be more successful and 6-dodecyne (28a), 7-tetradecyne (29a) and 2,9-dimethyl-5-decyne (30a) were fully converted to corresponding alkenes with 90 to 99% yields (Table 3, 28b-30b). The two isomers of 5decenol (31b) are known to be hormones of the Peach Twig Borer and the Lepidoptera, respectively, and can be encountered in different industrial formulations of pesticides and fragrances. 30 Interestingly, the presence of a primary alcohol in the corresponding precursor 31a was tolerated and quantitatively transformed into the corresponding alkene 31b with 99% isolated yield and a 3:1 E/Z ratio (Table 3, 31b). Notably, double bond migration was not observed in any case. Table 3. Mn1 catalyzed semihydrogenation of alkyl-alkyl alkynes a a Reaction conditions: alkyne (0.9 mmol, 1 equiv), Mn1 (2 mol%), KBH4 (0.5 equiv), MeOH (3.7 mL, 100 equiv), 90°C, 20 h, isolated yields. Values in the brackets correspond to the E/Z ratio determined by 1 H NMR spectroscopy. b Yield determined by GC-MS using dodecane as intenal standard. c Mn1 (1 mol%).
Terminal alkynes display another challenging class of substrates in semihydrogenation due to over hydrogenation yielding alkanes as well as dimerization to afford 1,3-enynes. 28 However, it was possible to achieve 49% yield of styrene (Table 4, 32b) upon increasing the catalyst loading to 2 mol%. Under the optimized reaction conditions, heterosubstituted phenylacetylenes were fully hydrogenated albeit with moderate selectivity (Table 4).
Mechanistic studies were carried out to gain insights in the reaction mechanism (Scheme 3). Upon addition of PPh3 only traces of E/Z-stilbene were obtained. This is attributed to coordination of PPh3 to the manganese center blocking a vacant side of the catalyst. This again indicates that an inner-sphere mechanism is operating in this system. Furthermore, deuterium labelling experiments were performed. If 1a was treated with KBH4 in MeOH-d1, a deuterium content of 81% was observed in E-stilbene. This amount of deuterium incorporation did not change significantly when MeOH-d4 was used instead. As expected, up to 97% deuterium content was incorporated when 1a was treated with NaBD4 in MeOH-d4. In contrast, only a negligible amount of merely 9% deuterium was incorporated when NaBD4 was used in combination with MeOH. When Z-stilbene (1c) was treated with NaBD4 in MeOH-d4 only a deuterium content of 57% was observed in the isomerized product. These observations clearly show that the acidic proton of MeOH is almost exclusively incorporated into the substrate presumably via fast proton exchange with hydride intermediates shown the catalytic cycle (vide infra). 31 Table 4. Mn1 catalyzed semihydrogenation of terminal alkynes a a Reaction conditions: alkyne (0.4 mmol, 1 equiv), Mn1 (2 mol%), KBH4 (0.3 equiv), MeOH (3.5 mL, 150 equiv), 90°C, 20 h, yield corresponds to alkene (b), values in brackets correspond to yield of saturated alkane (c) as determined GC-MS using dodecane as internal standard. A plausible catalytic cycle based on experimental data and DFT calculations (PBE0/(SDD,6-31G**)) 32 with diphenylacetylene (1a) as model substrate could be established. The resulting free energy profiles are represented in Figures 1 and 2 while Scheme 4 depicts the simplified catalytic cycle (only key intermediates are shown).
The activation of Mn1 by dihydrogen has been reported recently. 24 Substitution of the weakly-bonded n-butanal by 1a leads to formation of the hydride species A featuring an η 2 -bound acetylene ligand (free energy values are referred to this complex). Insertion of the acetylene into the Mn-H bond affords the coordinatively unsaturated vinyl complex B which is stabilized by an agostic C-H bond. This process is exergonic by -23.8 kcal/mol with a very small barrier of 0.6 kcal/mol. Addition of dihydrogen leads via the van der Waals adduct C to the formation of intermediate D. This step is endergonic by 9.9 kcal/mol with an overall barrier of 18.6 kcal/mol being the highest of the entire cycle. Heterolytic cleavage of dihydrogen results in the formation of the hydride complex E featuring a C-H bound Z-stilbene in an exergonic step (ΔG = -9.4 kcal/mol) with a negligible barrier of 1.8 kcal/mol. The reaction proceeds with reorientation of the olefin from the C-H σ-complex in E to the π-coordinated complex in H. This process proceeds via intermediates F and G which are equivalent van der Waals pairs of the Z-stilbene and the metallic fragment. It involves olefin dissociation, clockwise rotation of the olefin by about 90 o and recoordination of the olefin. The overall process has a negligible barrier of 1.2 kcal/mol and is favorable with ΔG = -7.1 kcal/mol, reflecting the stronger coordination of the η 2 -olefin in H compared to the C-H σ-bound olefin in complex E.

CONCLUSION
In sum, an efficient protocol for the selective semihydrogenation of aryl-aryl, aryl-alkyl and terminal alkynes to afford E-alkenes is described. The pre-catalyst is the bench-stable alkyl complex fac-Mn(dippe)(CO)3(CH2CH2CH3) in combination with KBH4 and MeOH as hydrogen source. The hydrogen gas required for the hydrogenation is formed in situ upon alcoholysis of KBH4. Thus, high pressure equipment is not required. The reaction proceeds at 90 o C with catalyst loadings of 0.5 to 2.0 mol% and a reaction time of 20 h. This represents a rare example of a manganese catalyzed hydrogenation of alkynes to give selectively E-alkenes. High functional group tolerance including halides, phenols, nitriles, unprotected amines and heterocycles was observed. Even challenging substrates such as alkyl-alkyl alkynes and terminal alkynes allowed high conversions with moderate to good selectivity. The practical applicability of the protocol was demonstrated in the gram-scale synthesis of E-stilbene. Mechanistic investigations including DFT calculations and deuterium labelling studies were undertaken to provide a reasonable reaction mechanism showing that initially formed Z-isomer undergoes fast isomerization to the afford the thermodynamically more stable E-isomer.