Palladium-Catalyzed Heck Alkynylation of Benzyl Chlorides

Catharine H. Larsen, Kevin W. Anderson, Rachel E. Tundel, Stephen L. Buchwald*

*Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA, Email: sbuchwalmit.edu

C. H. Larsen, K. W. Anderson, R. E. Tundel, S. L. Buchwald, Synlett, 2006, 2941-2946.

DOI: 10.1055/s-2006-949625

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Abstract

An efficient protocol for the palladium-catalyzed Heck alkynylation using XPhos as ligand and Cs₂CO₃ as the base, couples a wide range of functionalized terminal alkynes and substituted benzyl chlorides. An excess amount of base and higher reaction temperatures allows the synthesis of allenes in a one-pot procedure.

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Details

The article by Catharine H. Larsen et al. presents a protocol for the palladium-catalyzed Heck alkynylation of benzyl chlorides. The catalyst system, consisting of PdCl₂(CH₃CN)₂ and XPhos, with Cs₂CO₃ as the base, effectively couples various functionalized terminal alkynes and substituted benzyl chlorides at 65°C. This method avoids the need for a copper co-catalyst and prevents the formation of undesired allene products. The study demonstrates that using excess base and higher temperatures (80°C) can selectively produce aryl allene products in a one-pot procedure. The protocol is versatile, accommodating a wide range of terminal alkynes, including aryl, heteroaryl, and aliphatic alkynes, and various benzyl chlorides with different substituents. The reaction conditions are optimized to ensure high yields and minimal side products. The research expands the scope of palladium-catalyzed cross-coupling reactions, providing a reliable method for synthesizing benzyl alkynes and aryl allenes, which are valuable in organic synthesis. The work is supported by the National Institutes of Health and highlights the potential applications of this methodology in modern synthetic chemistry.

Key Words

palladium, alkynes, alkynylation, arylmethanes, Heck alkynylation, benzyl chlorides, allenes

ID: J60-Y2006-4740