Organocatalytic enantioselective synthesis of dihydronaphthofurans and dihydrobenzofurans: reaction development and insights into stereoselectivity

Abstract

Squaramide/cinchona alkaloid-derived bifunctional organocatalysts are in high demand in asymmetric transformations. Bifunctional quinine-derived sterically encumbered squaramide (H-bond donor) organocatalysts were used to catalyze the asymmetric Friedel–Crafts/S_N2 type domino reaction of (Z)-α-bromonitroalkenes and α/β-naphthols and phenol derivatives to generate enantiomerically enriched dihydronaphthofuran (DHN) and dihydrobenzofuran (DHB) derivatives, respectively. The target adducts were obtained in up to >99% ee under mild conditions with a relatively low catalyst loading (5 mol%) compared to the methods known in the literature. In addition, density functional theory (DFT) calculations were performed to establish a possible outcome, explaining the origin of the stereoselectivity. It was discovered that π-stacked interactions for the trans-conformation in the Friedel–Crafts step are 0.79 kcal mol⁻¹ more stable than the cis-conformation.