Metal Triflates: Efficient Catalysts for Oxa-Pictet-Spengler Reaction

Abstract

A screening of different metal triflates as catalysts was performed to get isochromans through an oxa-Pictet- Spengler reaction. Good to high yields were obtained for various aliphatic or aromatic aldehydes and  -arylethanols. A mechanism involving catalysis by in situ liberated triflic acid to catalyse the isochroman ring formation is proposed. In the previous work, we described the synthesis of iso(thio)chromans from 2-phenylethanol derivatives or 2- phenylethanethiol and different aldehydes in the presence of catalytic amounts of bismuth(III) triflate (9). The catalytic activity of Bi(OTf)3 could be attributed to traces of triflic acid generated in situ (10). The numerous advantages of metal catalysts make them highly attractive for chemical synthesis from environmental and economic points of view. In this study, we disclose the usefulness of metal triflate to provide isochroman from  -aryl ethanol. This work provides also insights into the catalytic role of metal triflates in the reaction. We have also examined the scope of the reaction in the presence of different reactants. Initially, the condensation of 3,4-dimethoxyphenyl ethanol (1 eq) and 4-nitrobenzaldehyde (1 eq) was used as a model reaction for the screening of seven different metal triflate catalysts. The reaction was carried out in toluene at 80°C in the presence of a catalytic amount (0.01 eq) of metal triflate. The reaction was monitored by TLC analysis following the disappearance of the starting alcohol. The reaction was completed in maximum 1.5h and isochroman was obtained in almost quantitative yield (entries 2-8, Table 1) after work- up and silica gel purification. The same reaction was realized in the absence of metal to recover essentially the starting material and the isochroman product in 16% yield after 18 hours (entry 1, Table 1).