Asymmetric synthesis of chromans via the Friedel–Crafts alkylation–hemiketalization catalysed by an N,N′-dioxide scandium(iii) complex

Abstract

An enantioselective tandem Friedel–Crafts alkylation–hemiketalization between electron-rich phenols and α,β-unsaturated ketoesters gave a direct approach to chiral 2,3-disubstituted chromans in the presence of a chiral N,N′-dioxide/Sc(OTf)₃ complex. High enantioselectivities (up to 95% ee), high diastereoselectivities (up to 14 : 1) and high yields (up to 97%) were obtained for a broad range of substrates under mild reaction conditions.