Environmentally benign, microwave-assisted chemoselective Nhydroxyalkylation of indoles with trifluoroacetaldehyde methyl hemiacetal

The chemoselective microwave-activated N-hydroxyalkylation of indoles using trifluoroacetaldehyde methylhemiacetal as the alkylating agent under mild conditions is described. The chemoselectivity of this reaction is determined by the solvent used. In dimethyl sulfoxide, the reaction occurs without the use of a strong base or a metal catalyst. This approach can be applied to a variety of different substituted indoles to obtain the corresponding N-alkylated products with high selectivity. The product 2,2,2-trifluoro-1-(1-H-indol-1-yl)ethanols combine two moieties of frequent pharmacological interest: the indole core and a CF₃-group containing a hydroxyalkyl substituent.