Highly Chemoselective Synthesis of Purino[3,2-c]oxazoles via the Asymmetric Dearomative [3+2] Cycloaddition of Purines with Donor-Acceptor Oxiranes

A Ni(II)/bisoxazoline-catalyzed asymmetric dearomative [3+2] cycloaddition of substituted purines with donor- acceptor oxiranes was developed. This reaction, which proceeds via highly chemoselective C-C bond cleavage of the oxiranes, accesses chiral purino[3,2-c]oxazole compounds (<= 99% ee after enrichment via crystallization). The electronic effects of the purine ring determine the reactivity of the substrate. The general applicability of this method was illustrated by gram-scale synthesis, the diverse transformations of the product, and the promising biological activities of selected derivatives.