Modular synthesis of chiral homo- and heterotrisoxazolines. Improving the enantioselectivity in the asymmetric Michael addition of indole to benzylidene malonate

A simple approach to a diverse set of chiral trisoxazolines is described. Deprotonation of bisoxazolines 2, followed by treatment of 2- chloromethyloxazolines 3, affords chiral trisoxazolines, including chiral homo- and hetero-trisoxazolines in good to high yields. These trisoxazolines are successfully applied in the asymmetric reaction of indole with benzylidene malonate, and ee's up to 93% were obtained.