Part 1. Studies on C-H Functionalization of β-Heteroatom-Substituted Ketones and Chromone derivatives
Chromone, cyclic enolone, and cyclic enaminone motifs are prevalent in a plethora of natural and synthetic compounds which display a variety of biological activities. To expand biologically important compound libraries, we have developed efficient methods for constructing flavone motif through C-H functionalization with a various transition metal catalytic system.
1.1 Palladium-Catalyzed Dehydrogenation/Oxidative Cross-Coupling Sequence of β-Heteroatom-Substituted Ketones
The one-pot sequence allows formation of the enone functionality and subsequent cross-coupling reaction. The process provides access to highly functionalized cyclic enolones and enaminones from readily accessible β-heteroatom-substituted cyclic ketones.
1.2 Synthesis of Heterocyclic-Fused Benzofurans via C-H Functionalization of Flavones and Coumarins
An efficient method to effect C?O cyclization was developed via the C-H functionalization of chromones and coumarins, affording heterocyclic-fused benzofurans.
1.3 A Facile Route to Isoflavone Quinones via the Direct Cross-Coupling of Chromones and Quinones
A straightforward and efficient method for the palladium-catalyzed direct cross-coupling of chromones with various quinones has been developed to rapidly construct isoflavone quinone structural motifs.
Keywords: C-H functionalization, cross-coupling, dehydrogenation, heterocycles, palladium, chromones, coumarins, benzofurans, isoflavone quinones, quinones
Part 2. Rhodium(III)-Catalyzed Direct C-H/C-H Cross-Coupling of Quinones with Arenes assisted by a Directing Group: Identification of Carbazole Quinones as GSKβ Inhibitors
Rhodium(III)-catalyzed direct C?H/C?H cross-coupling reaction of various (hetero)arenes with quinones is developed. This protocol is effective for a broad range of both quinone and arene substrates and a wide range of directing groups for this reaction, affording structurally diverse aryl-substituted quinones with high synthetic utility. Moreover, the present synthetic route allowed for the rapid construction of the carbazole quinone moiety that was identified as a new inhibitor scaffold for GSKβ.
Keywords: Rhodium, directing group, quinone, GSKβ inhibitors
Part 3. Divergent Reactivity in Palladium-Catalyzed Arylation with Pyridotriazoles: One-Pot Synthesis of 6-Aryl-2-α-styrylpyridines
We developed a new strategy of the palladium-catalyzed arylation reactions with pyridotriazoles in different reaction patterns (C3 vs C7), wherein unprecedented and remarkable switching in chemical transformations is controlled by the action of base. The reactive palladium carbenoids were directly generated from pyridotriazoles and underwent arylations with aryl bromides via migratory insertion of aryl groups to the carbenic carbon. Intriguingly, when $K_2CO_3$ was replaced with tBuOK, direct C-H arylation occurred at the most acidic position (C7). Moreover, two different arylation events were successfully conducted in a one-pot catalytic process, providing access to 6-aryl-2-α-styrylpyridines.
Keywords: Palladium, pyridotriazole, carbene, arylation, one-pot reaction