Amine- and phosphine-free palladium(II)-catalyzed homocoupling reaction of terminal alkynes
Graphical Abstract
Introduction
Diynes are useful building blocks in organic synthesis and a recurring functional group in many natural products and bioactive compounds.1, 2, 3 As a result, considerable effort has been directed to the development of new and efficient methods for the synthesis of diynes since 1869.3, 4, 5, 6 Palladium-catalyzed homocoupling reaction of terminal alkynes transformation represents one of the most attractive routes to synthesize symmetrical diynes due to their mildness and efficiency.3, 6 This homocoupling method is generally carried out in the presence of phosphine ligands (Ph3P) and amines (for example, i-Pr2NH, i-Pr2NEt, Dabco, and Et3N). For example, Zhang and co-workers6f have reported an efficient protocol for homocoupling of alkynes using PdCl2(PPh3)2, CuI, ethyl bromoacetate and amine (triethylamine or Dabco) as the catalytic system. Fairlamb and co-workers6g have also described an efficient PdCl2(MeCN)2 and CuI catalyzed homocoupling of alkynes procedure in Et3N/MeCN, and more loadings of PPh3 were required to improve the reaction. Generally, phosphine ligands are generally sensitive to air and expensive which puts significant limits on their synthetic applications.7 Amines also have characteristic foul smell and pungent flavor. For these reasons, the development of an effective procedure for homocoupling of alkynes under amine- and phosphine-free conditions would be significant. Here, we report our findings that PdCl2, in combination with CuI, Me3NO (as the reoxidant), and NaOAc (instead of amines as the base), was proven to be an extremely effective catalytic system for the homocoupling of various terminal alkynes.
Section snippets
Palladium-catalyzed homocoupling of phenylacetylene (1a)
To evaluate the efficiency of PdCl2/CuI/Me3NO, homocoupling of phenylacetylene (1a) was tested in the absence of any phosphine ligands, and the results were summarized in Table 1. The results showed that the combination of PdCl2, CuI, and Me3NO was an effective catalytic system for the reaction. Initially, several bases including NaOAc, Na2CO3, Et3N, and pyridine were examined, and the results indicated that NaOAc was the most effective (entries 1–7). Treatment of phenylacetylene (1a) with PdCl2
Conclusion
In summary, we have developed a mild and efficient protocol for homocoupling of various terminal alkynes in the presence of PdCl2, CuI, Me3NO and NaOAc. This Pd(II)-catalyzed procedure not only tolerates a range of functional groups, but also does not require any phosphine ligands. Currently, further efforts to study the mechanism and apply the new approach in organic synthesis are underway in our laboratory.
General methods
1H and 13C NMR spectra were recorded on an INOVA-400 (Varian) spectrometer with CDCl3 as the solvent. All reagents were directly used as obtained commercially.
Typical experimental procedure for the palladium-catalyzed homocoupling of alkynes
A mixture of alkyne 1 (1 mmol), PdCl2 (5.6 mol%), CuI (2.5 mol%), Me3NO·2H2O (2 equiv), NaOAc (3 equiv), and MeCN (5 mL) was stirred under N2 at room temperature until complete consumption of starting material as judged by TLC and GC analysis. After the mixture was filtered and evaporated, the residue was purified by flash column chromatography
Acknowledgements
We thank the National Natural Science Foundation of China (No. 20202002), Education Department of Hunan Province (No. 02C211) and Hunan Normal University (2001) for the financial support.
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