Highly chemoselective conjugate addition of lithium tetraorganozincates to coumarin derivatives and functionalization with electrophiles

Abstract

The nucleophilic addition (alkylation/arylation) of lithium tetraorganozincate species (R4ZnLi2) to coumarin derivatives takes place cleanly, with a short reaction time (30 min) and with high chemoselectivity, when working under mild conditions (0 °C) and with no additional solvents. Particularly remarkable is the diastereoselectivity of the reaction (up to 96:4), after trapping the resulting intermediates with external electrophiles. The stereochemistry of the major trisubstituted stereoisomer was assigned by combining 2D NOESY experiments with DFT calculations.