Tröger’s Base Derivative-catalyzed Ugi-Smiles Reaction Involving Aliphatic Aldehydes

Ugi-Smiles reactions play an important role in the field of organic synthesis and pharmaceutical chemistry. However, due to their low reactivity, less electrophilic aliphatic aldehydes have never been used as substrates. To expand the range of substrates for the reaction, a bis(N-(pyridin-2-ylmethyl)aminomethyl substituted Tröger's base derivative was used to promote the Ugi-Smiles reaction involving aliphatic aldehydes. With the facilitation of the catalyst, the reaction of isocyanides, malononitrile, aldehydes, and low-reactive, unfunctionalized 1H-benzo[d]imidazole-2-thiols proceeded smoothly to afford thioimidazolidinones in high yields under mild conditions. Both experimental and theoretical calculations showed that the catalyst's high catalytic activity may be due to its appropriate cavity size and alkalinity, as well as its multiple catalytic active sites.