Cross-Coupling of Nonactivated Alkyl Halides with Alkynyl Grignard Reagents: A Nickel Pincer Complex as the Catalyst

摘要

Alkynes are an important class of organic molecules because they are frequently used as synthetic intermediates and precursors for natural products, biologically active molecules, and organic materials. Alkynes are also essential coupling partners for the azide-alkyne Huisgen cycloaddition reac-tion. The streamlined synthesis of alkynes containing various functional groups is therefore highly desirable. Alkynes containing nonactivated alkyl groups, especially those with β-hydrogen atoms, are difficult to synthesize. Reactions of alkali metal acetylides with alkyl halides in liquid ammonia, or with hexamethylphosphoramide (HMPA) as the solvent or cosolvent at a low temperature (e.g., —78 °C), have long been used for the alkylation of alkynes. These reactions suffer from the limited solubility of acetylides in liquid ammonia, the carcinogenic effect of HMPA, and the inconvenience of working at low temperatures.