Spatiotemporal Control of Pre-existing Alkene Geometry: A Bio-Inspired Route to 4-Trifluoromethyl-2H-chromenes

Routes to prepare C4-trifluoromethyl analogues of the 2H-chromene scaffold are scarce: this is particularly striking given the importance of fluorine in pharmaceutical development. To address this limitation, a facile strategy has been developed that is reliant on catalytic, geometric isomerization of easily accessible allylic alcohols (up to >95:5) followed by intramolecular cyclization via Pd catalysis (up to 96%). This concise biomimetic approach emulates the photoisomerization/cyclization cascade inherent to phenylpropanoid biosynthesis.