Box-copper catalyzed asymmetric inverse-electron-demand oxa-hetero-Diels–Alder reaction for efficient synthesis of spiro pyranyl-oxindole derivatives

Abstract

Spiro oxindole-pyran backbones are structural motifs widely occurring in natural products and bioactive synthetic compounds. In this paper, we present the asymmetric catalytic synthesis of three series of spirooxindole-pyran derivatives via an inverse-electron-demand oxa-hetero-Diels–Alder (IEDDA) reaction in the presence of 2.5–10 mol% of chiral bisoxazoline/copper(II) complexes as Lewis acid catalysts. Under mild reaction conditions, the IEDDA reactions of isatin-derived β,γ-unsaturated α-ketoesters with some dienophiles, such as 2,3-dihydrofuran, 3,4-dihydro-2H-pyran and ortho-vinylphenols, respectively, furnished the corresponding chiral spiro oxindole-pyrans in excellent yields with excellent diastereo- and enantioselectivities.