Microwave-Assisted Synthesis of Guanidine Organocatalysts Bearing a Tetrahydroisoquinoline Framework and Their Evaluation in Michael Addition Reactions

The simple and practical syntheses of chiral guanidine organocatalysts and their evaluation in the asymmetric Michael addition reaction of malonates and beta-keto esters with nitro-olefins is reported. These organocatalysts are the first of their kind based on a tetrahydroisoquinoline framework. In addition, a microwave-assisted procedure for introducing the guanidine unit onto amino amide derivatives is reported. The chiral products were obtained with quantitative chemical efficiency (up to 99 % yield) and excellent enantioselectivity (up to 97 % ee).