Catalytic asymmetric substitution of ortho-hydroxybenzyl alcohols with tetronic acid-derived enamines: enantioselective synthesis of tetronic acid-derived diarylmethanes

Abstract

The first catalytic asymmetric substitution of ortho-hydroxybenzyl alcohols with enamines has been established, which afforded tetronic acid-derived diarylmethanes in considerable yields and good enantioselectivities (up to 89% yield, 98 : 2 er). This reaction not only provided an efficient method for enantioselective synthesis of tetronic acid-derived diarylmethanes with biological relevance, but also fulfilled the task of developing catalytic asymmetric substitution of ortho-hydroxybenzyl alcohols by using tetronic acid-derived enamines as competent nucleophiles. More importantly, the preliminary biological evaluation of some selected products revealed that this class of chiral tetronic acid-derived diarylmethanes exhibited strong cytotoxicity to HT-29, MCF-7 and TE-13 cancer cell lines.