Pd/C-catalyzed alkynylation of β-chloroacroleins

doi:10.1016/j.tet.2007.10.013

Tetrahedron

Volume 63, Issue 52, 24 December 2007, Pages 13018-13023

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Abstract

The first Pd/C-mediated Sonogashira coupling of β-chloroacroleins with terminal alkynes is described here. Pd/C–CuI–PPh₃ was found to be an efficient catalyst system for this coupling reaction. Using this economic and general process a variety of 4-alkynyl-2H-chromene-3-carbaldehydes and 5-alkynyl-2,3-dihydro benzo[b]oxepine-4-carbaldehydes were prepared in good yields.

Graphical abstract

Introduction

Transition metal mediated cross-coupling reactions are among the most powerful carbon–carbon bond forming reactions in organic synthesis. Among them, those involving palladium catalysis especially alkynylation of sp² species such as aryl and alkenyl halides (the Sonogashira coupling)1, 1(a), 1(b) are particularly useful for the preparation of arylalkynes or conjugated enynes, owing to excellent levels of selectivity and high functional group compatibility. Based on various halides used in Sonogashira reactions the general reactivity order of the sp² species can be presented as vinyl iodide≥vinyl triflate>vinyl bromide>vinyl chloride>aryl iodide>aryl triflate≥aryl bromide≥aryl chloride.^1b Thus the Sonogashira alkynylation process usually proceeds smoothly when the more reactive but more expensive vinyl and aryl iodides are used. Notably, vinyl chloride although less reactive amongst the vinyl halides is more reactive than aryl iodides and therefore has been utilized in the synthesis of natural products and numerous biologically active compounds.2, 2(a), 2(b), 2(c) Despite its potential utility, the use of β-chloroacroleins (–CCl double bond CCHO–) in cross-coupling reaction has not been explored until recently3, 3(a), 3(b) and to the best of our knowledge only four examples involving the use of β-chloroacroleins under Sonogashira condition have been reported.4, 4(a), 4(b) Because of its cheap availability and high catalytic activity,5, 5(a), 5(b), 5(c) Pd/C has been used in Sonogashira coupling by us and several other groups.⁶ Herein we report a very facile and general method for the alkynylation of β-chloroacroleins under Pd/C–copper catalysis.

Section snippets

Results and discussion

To determine the feasibility of this approach, 4-chloro-2H-chromene-3-carbaldehyde (1, n=1, Z=H) was treated with terminal alkynes (2, R=alkyl, hydroxyalkyl, aryl, etc.) in acetonitrile in the presence of 10% Pd/C (0.026 equiv), PPh₃ (0.12 equiv), CuI (0.05 equiv), and Et₃N (3.0 equiv) under nitrogen. The reaction proceeded well and 4-alkynyl-2H-chromene-3-carbaldehydes (3, n=1, Z=H) were obtained in good to excellent yields (Scheme 1). The results are summarized in Table 1.

While acetonitrile was

Conclusion

In conclusion, we have demonstrated that Pd/C–CuI–PPh₃ can be used as an efficient catalyst system for Sonogashira coupling of β-chloroacroleins with terminal alkynes. The reactions proceed well to afford a variety of 4-alkynyl-2H-chromene-3-carbaldehydes and 5-alkynyl-2,3-dihydro benzo[b]oxepine-4-carbaldehydes in good yields. This is a general and economical process and opens an easy way to access alkynyl substituted acroleins. Since the development of effective methods for the

General methods

Unless stated otherwise, reactions were performed in dried glassware under a nitrogen atmosphere. All the solvents used were commercially available and distilled before use. Reactions were monitored by thin layer chromatography (TLC) on silica gel plates (60 F254; Merck), visualizing with ultraviolet light or iodine spray. Flash chromatography was performed on silica gel (SRL 230–400 mesh) using distilled petroleum ether, ethyl acetate, dichloromethane, chloroform, and methanol. ¹H and ¹³C NMR

Acknowledgements

The authors thank Dr. V. Dahanukar and Mr. A. Mukherjee for their encouragement and the analytical group for spectral data. R.B. thank CPS-DRL, Hyderabad, India for allowing him to pursue this work as a part of his Ph.D. program.

References and notes (7)

K. Sonogashira et al.
Tetrahedron Lett.
(1975)
R. Chinchilla et al.
Chem. Rev.
(2007)
Z. Arnold et al.
Collect. Czech. Chem. Commun.
(1959)
J. Burdon et al.
J. Chem. Soc., Chem. Commun.
(1967)
B. Konig et al.
Synthesis
(1996)
M.C. Joshi et al.
ARKIVOC
(2006)

There are more references available in the full text version of this article.

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Pd/C-catalyzed alkynylation of β-chloroacroleins

Abstract

Graphical abstract

Introduction

Section snippets

Results and discussion

Conclusion

General methods

Acknowledgements

Tetrahedron Lett.

Chem. Rev.

Collect. Czech. Chem. Commun.

J. Chem. Soc., Chem. Commun.

Synthesis

ARKIVOC