The Ru(II)-Catalyzed Catalytic Additive-Controlled Selectivity Switch between Mono-olefination and Dehydrogenative Annulation of 3-Aryl-4(3 <i>H</i> )-quinazolinone: Access to Products of Different Chemotypes

A regiodivergent synthesis leading to products of different chemotypes, mono-olefination vs dehydrogenative annulation, has been achieved through Ru(II)-catalyzed C-H activation at three dissimilar C-H bonds of the 3-aryl-4(3<i>H</i>)-quinazolinone scaffold with cyclic structurally nonflexible free NH- and N-substituted maleimides. The alteration of selectivity between two chemotypes could easily be regulated via the absence or presence of catalytic AcOH. The strategy provides a broad substrate scope concerning coupling partners, excellent chemo-/regioselectivity, and functional group tolerance and further offers scalability and synthetic elaboration of end products. Mechanistic studies reveal that mono-olefination and dehydrogenative annulation follow two independent reaction pathways. While mono-olefination at the C5-H site of 3-aryl-4(3<i>H</i>)-quinazolinone relies on weak coordination of O(carbonyl) as a directing unit, the dehydrogenative annulation at the C2-H/<i>ortho</i>-(NAr)C-H bonds operates via a cascade reaction sequence aided by catalytic AcOH. It is believed that an efficient coordination of the Ru(0) center to the (CO)O-atom of the tethered rigid maleimide framework plus the proximity of the <i>ortho</i>-(NAr)C-H site to the coordination zone of the Ru(0) center within a tight spatial arrangement is the principal requirement of successful dehydrogenative annulation. Structurally flexible open-chain activated olefins lack the organizational prerequisite and could deliver mono-olefination at the C5-H position as the sole product in the absence/presence of catalytic AcOH as an additive.