An efficient one-pot strategy evolved in the synthesis of (E)-4-benzylidenylacridin-1(2H)-ones, (4 or 9) (E)-2-styryl quinoline-3-carboxamides (5 or 10) by sequential Suzuki–Miyaura coupling-dehydrogenative Friedländer-sp3 C–H activation. The 2-amino-5-chloro benzhydrol 1, aromatic alcohol 2 or 6 ketones 3 or 3', and phenylboronic acid 7 underwent a smooth reaction in a basic deep eutectic solvent consisting of K2CO3 and ethylene glycol (DES-1,1:1). DES-1 could enable the Pd-catalyzed Suzuki coupling reaction of 6, as well as the rapid oxidation of primary, secondary, and Suzuki coupled primary alcohols (2, 1, and 8) in the presence of an iridium catalyst and 1,10-phenanthroline. The acidic DES-2 (dimethyl urea/tartaric acid, 7:3) assists the Friedländer annulation and subsequent sp3-C–H functionalization resulting in (E)-4-benzylidenylacridin-1(2H)-ones (4 or 9) and (E)-2-styryl quinoline-3-carboxamides (5 or 10). © 2020 Wiley-VCH GmbH