[a] Reactions were carried out with an iron source (0.036 mmol, 5 mol %), diphenylacetylene (0.72 mmol), borane (0.79 mmol, 1.25 equiv), in toluene (2.0 mL) at 100 °C. [b] The conversion and yield were determined by GC-MS (30 m Rxi-5 ms column, 40–300 °C) by applying n-dodecane as an internal standard. [c] Catecholborane was used as the borane source. [d] 70 °C. [e] room temperature. [f] THF, 70 °C. [g] 2 (2.0 equiv). [h] 100 mmol scale.
Straightforward Iron-Catalyzed Synthesis of Vinylboronates by the Hydroboration of Alkynes
Article first published online: 12 NOV 2012
Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chemistry – An Asian Journal
Volume 8, Issue 1, pages 50–54, January 2013
How to Cite
Haberberger, M. and Enthaler, S. (2013), Straightforward Iron-Catalyzed Synthesis of Vinylboronates by the Hydroboration of Alkynes. Chem. Asian J., 8: 50–54. doi: 10.1002/asia.201200931
- Issue published online: 20 DEC 2012
- Article first published online: 12 NOV 2012
- Manuscript Revised: 19 OCT 2012
- Manuscript Received: 4 OCT 2012
- Deutsche Forschungsgemeinschaft
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- homogeneous catalysis;
Olefins have a wide range of applications including, as building blocks for bulk chemicals, pharmaceuticals, agrochemicals, polymers, in the syntheses of natural products, and as key intermediates in organic syntheses.1 During the last decades, a number of methodologies have been established to access alkenes; of these transformations, the reduction of alkynes to produce alkenes is of relevance, because of the availability and straightforward synthesis of the starting materials.2 In this regard, the application of transition metal catalysts has been demonstrated as a useful tool to access olefins through, for example, hydrogenation, hydrosilylation, or hydroboration.3 Especially, the construction of functionalized olefins, such as vinylsilanes or vinylboranes, allow for further straightforward transformations, such as coupling reactions (Scheme 1).4 Up to now, manifold systems rely on precious metals, such as rhodium, ruthenium, iridium, or palladium. However, owing to the high price and sometimes toxicity, less-expensive metal-based catalysts are highly desirable. In this regard, the potential of iron has been recently proven.5 Moreover, one important aspect of the protocol should be to address the selectivity issues, as various isomers are feasible depending on the substitution pattern of the starting material (Scheme 1).6 Indeed, iron catalysts have been applied in the catalytic reduction of alkynes using molecular hydrogen as a reductant.7 On the other hand, promising efforts have been reported on hydrosilylation by the group of Chirik, who applied well-defined iron-complexes modified by tridentate nitrogen ligands to reduce alkynes with silanes to the corresponding alkene at ambient temperature.8 Furthermore, Plietker et al. realized the hydrosilylation of internal alkynes with [FeH(CO)(NO)(PPh3)2] as a precatalyst.9 Interestingly, depending on the kind of silane employed the stereochemistry of the products can be easily tuned. Recently, we reported the application of easily accessible iron phosphane complexes in the hydrosilylation of disubstituted alkynes under mild reaction conditions.10 In contrast, the iron-catalyzed hydroboration of alkynes has been not reported so far. However, the feasibility of the addition of boranes to an unsaturated system such as olefins in the presence of iron catalysts has been recently realized.11 Based on these results and our initial results in the iron-catalyzed hydrosilylation of alkynes, we wish to portray the application of a robust and easy-to-adopt iron-based catalyst for the highly selective hydroboration of alkynes to produce vinylboronates.
Preliminary studies on the influence of the reaction conditions were carried out with diphenylacetylene 1 as the model substrate by using 1.67 mol % of triiron dodecacarbonyl and pinacolborane 2 as reducing reagent in toluene at 100 °C (Table 1). After 24 h the reaction mixture was analyzed. Full conversion of the starting material was observed and the desired products were found in a ratio of 72:28 ((Z)-3/(E)-3; Table 1, entry 2). Noteworthy, the catalyst was highly selective towards the formation of the vinylboronates, while no over-reduction was observed (Table 1, entry 2). Moreover, catecholborane was applied as a hydroborane source. However, no product formation was achieved (Table 1, entry 3). Besides Fe3(CO)12, Fe2(CO)9 and Fe(CO)5 were also tested as precatalysts (Table 1, entries 5–8). Excellent performance was found for Fe2(CO)9 with >99 % conversion and a ((Z)-3/(E)-3) ratio of 93:7, while with Fe(CO)5 lower yields and selectivities were attained. Furthermore, various iron salts were investigated, but resulted in no product formation (Table 1, entries 9–11), whilst in the absence of any iron salts no product was detected (Table 1, entry 1). However, no progress was realized with respect to yield and selectivity. Decreasing the reaction temperature towards 70 °C or room temperature (Table 1, entries 12 and 13), respectively, did not improve the reaction outcome. By using tetrahydrofuran (THF) as solvent at 70 °C resulted in 68 % yield and 99 % Z-selectivity. Moreover, the influence of various nitrogen- (e.g., N,N,N′,N′-tetramethylethylenediamine (TMEDA), 2,2′-bipyridine, phenanthroline, imidazole) and phosphorous-containing ligands (e.g., PPh3, PBu3, 1,1′-bis(diphenylphosphino)ferrocene, diphenylphosphinoethane) were studied. However, in comparison to the unmodified iron carbonyl complexes no improvement was observed. Noteworthy, the system was easily scaled up to 100 mmol, and showed excellent conversion and good selectivity under non-inert conditions (Table 1, entry 16). The product was easily obtained by recrystallization from n-hexane–after removing the catalyst by filtration over a short plug of silica–in 82 % yield.
To explore the scope and limitations of the iron catalyst [Fe2(CO)9], a variety of alkyne substrates were tested under the reaction conditions given in Table 1, entry 6. First, various terminal phenylacetylenes were treated with pinacolborane 2 (Table 2, entries 1–9). Excellent yields and selectivities were observed for unsubstituted phenylacetylene (Table 2, entry 1). Interestingly, the corresponding E-isomer was exclusively formed by anti-Markovnikov and syn-addition of the borane reagent. Next, the influence of methyl substitution on the phenyl group was studied (Table 2, entries 2–4). Excellent performance was observed for para- and meta-substitution, while a decreased yield and selectivity was noticed for ortho-substitution. Moreover, substrates containing halide groups were reduced in excellent yields and selectivities (Table 2, entries 5–7). Difficulties were observed for benzylic and propargylic substrates (Table 2, entries 11 and 12). Furthermore, the effect of alkyl substituents was investigated, and showed excellent conversions (Table 2, entries 13–15). However, to some extent the corresponding Z-isomer (4–8 %) was detected. Interestingly, the iron catalyst showed excellent performance for a substrate containing a CC double bond in conjugation to the CC triple bond (Table 2, entry 14). Noteworthy, an exclusive reaction pathway for the hydroboration of the alkyne was observed. The hydroboration of substrates containing heteroaryls was successful for thiophene, while the pyridyl group probably inhibits the catalyst (Table 2, entries 16 and 17). In addition, disubstituted alkynes were also used (Table 2, entries 18–24). Noteworthy, for unsymmetrical alkynes four potential products are feasible. Indeed, for most substrates a mixture of the four possible isomers was observed. Unfortunately, separation and stereochemistry assignment of the mixture was not successful, owing to complexity. To study the selectivity of the hydroboration in the presence of substrates containing functional groups that are sensitive to reduction different substrates in combination with diphenylacetylene were treated with 2 in the presence of Fe2(CO)9 under optimized reaction conditions (Table 2, entries 26–29). Excellent selectivity (>99 %) for the hydroboration was observed in the presence of esters (yield: 73 % (Z)-3, 3 % (E)-3) and nitriles (yield: 81 % (Z)-3, 6 % (E)-3). In contrast, sulfoxide (yield: 8 % of the sulfide) and aldehyde (98 % of the alcohol) functionalities were reduced to some extent.
Moreover, the developed protocol was used in the synthesis of trisubstituted olefins (Scheme 2). First, the hydroboration of diphenylacetylene 1 was carried out as described in Table 2, entry 18. After isolation of the corresponding vinylboronate (Z)-3, a palladium-catalyzed cross coupling with different aryl halides was carried out.13 Addition of [Pd(PPh3)4] (5.0 mol %) and K2CO3 as a base afforded olefin 3 in good to excellent yield after 24 h at 120 °C. Noteworthy, in accordance to literature reports the E-isomer was observed almost exclusively.14
With respect to the reaction mechanism we have proposed a catalytic cycle that is in accordance to the hydroboration of alkenes as suggested by Ritter and co-workers (Scheme 3).11a First the alkyne coordinates to the iron center followed by an oxidative addition of the pinacolborane 2 to form the intermediate B. For the next step, different pathways can be discussed, on the one hand migratory insertion of the alkyne into the FeH bond (C) can take place or on the other hand into the FeB bond (D). Finally, a reductive elimination occurs to form the desired vinylboronate and by coordination of a new alkyne molecule the starting complex A is reformed.
In summary, we have reported a protocol for the efficient iron-catalyzed hydroboration of alkynes. With Fe2(CO)9 and pinacolborane a straightforward system was found, which is capable of producing a variety of vinylboronates in good to excellent yields and selectivities. Noteworthy, the reaction can be easily scaled up to 100 mmol to allow access to the products under non-inert conditions and this makes it probably interesting for organic synthesis.
General procedure for the catalytic hydroboration
A Schlenk flask was charged with an appropriate amount of Fe2(CO)9 (2.5 mol %), 2 (1.25 equiv, 1.57 mmol), and the corresponding alkyne (1.96 mmol). The flask was flushed with nitrogen under vacuum. Afterwards toluene (2.0 mL) was added. The flask was sealed and heated at 100 °C for 24 h. After that time, the mixture was cooled, and an aliquot was taken and dissolved in dichloromethane for GC-MS analysis. The products were confirmed by GC-MS and NMR spectroscopic analysis. Moreover, the products were purified by column chromatography (eluent: n-hexane/diethylether 10:1). The analytical properties of the products are in agreement with literature data.12
This work was supported by the Cluster of Excellence “Unifying Concepts in Catalysis” (sponsored by the Deutsche Forschungsgemeinschaft and administered by the Technische Universität Berlin). The authors thank Jörg Schmidt (TU Berlin) and Priya Anantharajah (TU Berlin) for technical support. Furthermore, Dr. Kathrin Junge (Leibniz Institut für Katalyse, Rostock) is thanked for donation of chemicals.
- 1aOrganic Syntheses Via Boranes, Vol. 3, Suzuki Coupling, Aldrich, Milwaukee, 2003;, ,
- 3aThe Handbook of Homogeneous Hydrogenation (Eds.: J. G. de Vries, C. J. Elsevier), 2006, Wiley-VCH, Weinheim;
- 3cOrganoboron Compounds, Vol. 219, 2002, Springer, Heidelberg, pp. 11–59.,
- 4bMetal-Catalyzed Cross-Coupling Reactions, Vol. 1 (Eds.: A. de Meijere, F. Diederich), Wiley-VCH, Weinheim, 2004, pp. 41–123.
- 5bIron Catalysis in Organic Chemistry (Ed.: B. Plietker), Wiley-VCH, Weinheim, 2008;
- 7iTetrahedron Lett. 1977, 18, 3947–3950;, ,
- 11For examples on hydroboration of olefins, see:
- 13For example, see:
- 15The stereochemistry of 3 d was assigned by single-crystal X-ray diffraction analysis (CCDC 909406 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data request/cif.)
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