Amine- and phosphine-free palladium(II)-catalyzed homocoupling reaction of terminal alkynes

doi:10.1016/j.tet.2004.12.026

Tetrahedron

Volume 61, Issue 7, 14 February 2005, Pages 1903-1907

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Abstract

An efficient, amine- and phosphine-free palladium(II)-catalyzed homocoupling of terminal alkynes has been developed. In the presence of PdCl₂, CuI, Me₃NO, and NaOAc, homocoupling of various terminal alkynes underwent smoothly to afford the corresponding diynes in moderate to high yields without any phosphine ligands. In contrast, the presence of a phosphine ligand (PPh₃) disfavored this palladium-catalyzed homocoupling procedure. Bases, solvents, and CuI have fundamental influence on the palladium-catalyzed homocoupling 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-workers^6f 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-workers^6g 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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Amine- and phosphine-free palladium(II)-catalyzed homocoupling reaction of terminal alkynes

Abstract

Introduction

Section snippets

Palladium-catalyzed homocoupling of phenylacetylene (1a)

Conclusion

General methods

Typical experimental procedure for the palladium-catalyzed homocoupling of alkynes

Acknowledgements

Phytochemistry

Arch. Pharm. Res.

Chem. Pharm. Bull.

Angew. Chem., Int. Ed.

J. Am. Chem. Soc.

J. Org. Chem.

J. Org. Chem.

Org. Lett.

Naturally Occurring Acetylenes

Ber. Dtsch. Chem. Ges.