Abstract:
An organocatalytic cascade vinylogous double 1,6-addition strategy for the synthesis of chiral chroman
derivatives is reported. The cascade reaction follows oxa-Michael/1,6-addition reactions between orthohydroxyphenyl-
substituted para-quinone methides and 2,4-dienal derivatives to deliver chroman derivatives
with excellent yields (up to 96%) and stereoselectivities (up to >20 : 1 dr, >99% ee). The chiral secondary
amine-based Jørgensen–Hayashi organocatalysts are shown to catalyze the transformation of
unbiased 2,4-dienals under mild reaction conditions with exclusive δ-site selectivity and high control over
enantioselectivity at a remote position. The synthetic transformations of the products ensure molecular
complexity with a great level of enantiocontrol.
