Diversity-Oriented Approach to N-Heterocyclic Compounds from α-Phenyl-ß-enamino Ester via a Mitsunobu-Michael Reaction Sequence.

ABSTRACT

Herein we delineate a novel route for the diastereoselective construction of diversely substituted N-heterocyclic ring systems as valuable scaffolds for natural products and pharmaceuticals, starting from an easily accessible prochiral α-phenyl-ß-enamino ester. The reaction sequence relies on the unexplored reactivity of α-phenyl-ß-enamino ester as a nucleophilic partner in the Mitsunobu reaction to forge the N-tethered alkene-alcohol/thiol/amine intermediate, which was subjected to an intramolecular hetero-Michael addition reaction under mild conditions to furnish the respective N-heterocyclic compounds embedded with an exocyclic chiral center in high yields and excellent diastereoselectivities. The methodology is amenable for a broad range of substrates based on a metal-free approach.