SnCl2-Catalyzed Propargylic Substitution of Propargylic Alcohols with Carbon and Nitrogen Nucleophiles

A weak Lewis acid, tin(II) chloride, which is insensitive to water and air, functioned as a catalyst for the propargylic substitution of secondary propargylic alcohols with carbon nucleophiles, such as electron-rich arenes, heteroarenes, and 1,3-dicarbonyl compounds, and nitrogen nucleophiles, such as sulfonamides, carbamates, and carboxamides, at 4080 degrees C in CH3NO2 under air and exhibited a higher catalytic activity than tin(II) bromide or iodide in the propargylic substitution of 1-phenyl-2-propyn-1-ol with anisole at 40 degrees C in CH3NO2. The solubility of tin(II) fluoride in CH3NO2 would have to be extremely low to cause no propargylic substitution. 1-Phenyl-substituted propargylic alcohols readily reacted with all these nucleophiles, whereas 1-(4-cyanophenyl)-2-propyn-1-ol and 1-(pentafluorophenyl)-2-propyn-1-ol did not react at all with 1,2,3-trimethoxybenzene even in CH3NO2 at reflux. The 1-alkyl-substituted secondary propargylic alcohol, 1,5-diphenyl-1-pentyn-3-ol, underwent SnCl2-catalyzed propargylic substitution with electron-rich arenes and amides, although the reaction was slow even at 80 degrees C in CH3NO2. Thus, the SnCl2-catalyzed propargylic substitution reaction is dependent upon the stability of the propargylic carbenium ion formed upon elimination of hydroxide from the corresponding propargylic alcohol.