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

• Published in: European journal of organic chemistry Vol. 2013; no. 14; pp. 2914 - 2921
• Main Authors: Masuyama, Yoshiro, Hayashi, Miki, Suzuki, Noriyuki
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01.05.2013; WILEY‐VCH Verlag; Wiley; Wiley Subscription Services, Inc
• Subjects: Alkynes; Chemistry; Chemistry, Organic; Lewis acids; Nucleophilic substitution; Physical Sciences; Propargylation; Science & Technology; Tin; Propargylation; ACTIVATION; ALKYLATION; COMPLEXES; Lewis acids; SULFONAMIDES; AROMATIC-COMPOUNDS; ALLYLATIONS; ALLYLIC ALCOHOLS; CATALYZED DIRECT SUBSTITUTION; Tin; Nucleophilic substitution; Alkynes; 1,3-DICARBONYL DERIVATIVES; 2-PROPYNYL ALCOHOLS
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201201673

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 40–80 °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 °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 °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. 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.