Copper Catalyzed [3+2] Annulation Reaction of Exocyclic Sulfonyl Enamides for the Synthesis of N,O-Spiroketal and Spiroketal

Abstract

A copper-catalyzed [3+2] annulation reaction of exocyclic enamines/enol ethers with 1,4-benzoquinone esters has been developed, providing facile access to N,O-spiroketals and spiroketals under mild conditions with broad substrate scope (26 examples, 71-94 % yields). Gram scale synthesis and chemical transformations demonstrated that this method is potentially useful in the synthesis of natural products and drugs containing a N,O- spiroketal moiety. The chiral N,O-spiroketal could be obtained with 98 % ee after recrystallization, when a chiral SaBOX ligand was employed.

Keywords: Annulation; Chiral N,O-spiroketal; Exocyclic sulfonyl enamides; [3+2]; copper catalysis.