The First Applications of Carbene Ligands in Cross-Couplings of Alkyl Electrophiles: Sonogashira Reactions of Unactivated Alkyl Bromides and Iodides
Matthias Eckhardt and Gregory C. Fu*
*Department of Chemistry, Massachusetts Institute of Technology, Cambridge,
Massachusetts 02139, Email: gcf
mit.edu
M. Eckhardt, G. C. Fu, J. Am. Chem. Soc., 2003, 125, 13642-13643.
DOI: 10.1021/ja038177r
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Abstract
A Pd/N-heterocyclic carbene-based catalyst achieves the Sonogashira coupling of an array of functionalized, β-hydrogen-containing alkyl bromides and iodides under mild conditions.
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Details
The document discusses the development of a Pd/N-heterocyclic carbene-based catalyst for Sonogashira reactions involving unactivated alkyl bromides and iodides. Traditionally, Sonogashira reactions, which couple terminal alkynes with aryl or vinyl halides, have not been effective with alkyl electrophiles due to issues like β-hydride elimination. Previous catalysts used phosphine ligands, but these were ineffective for alkyl bromides and iodides. The new catalyst system, which uses N-heterocyclic carbene ligands, successfully facilitates these reactions under mild conditions, achieving moderate to good yields. This advancement opens new possibilities for incorporating alkynes into organic molecules, which are important in natural products and bioactive compounds. The study highlights the potential for further development of nonphosphine-based catalysts for cross-coupling reactions, enhancing the functional-group compatibility and efficiency of these processes. The research was supported by Boehringer Ingelheim, NIH, Merck, and Novartis, and detailed experimental procedures and data are available online.
Key Words
ID: J48-Y2003-1670
