Rh(III)-catalyzed direct C-H/C-H cross-coupling of quinones with arenes assisted by a directing group: identification of carbazole quinones as GSKß inhibitors.

Rh-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 GSKß.

Synthesis of heterocyclic-fused benzopyrans via the Pd(II)-catalyzed C-H alkenylation/C-O cyclization of flavones and coumarins.

An efficient and practical method for effecting a tandem C-H alkenylation/C-O cyclization has been achieved via the C-H functionalization of flavone derivatives. The synthetic utility of the one-pot sequence was demonstrated by obtaining convenient access to coumarin-annelated benzopyrans. The reaction scope for the transformation was found to be fairly broad, affording good yields of a wide range of flavone- or coumarin-fused benzopyran motifs, which are privileged structures in many biologically active compounds.

Palladium-catalyzed dehydrogenation/oxidative cross-coupling sequence of ß-heteroatom-substituted ketones.

Concise and selective: the title one-pot sequence allows formation of the enone functionality and subsequent cross-coupling. The process provides access to highly functionalized cyclic enolones and enaminones from readily accessible ß-heteroatom-substituted cyclic ketones.

Tandem Dehydrogenation/Oxidation/Oxidative Cyclization Approach to Wrightiadione and Its Derivatives.

Wrightiadione contains a unique tetracyclic isoflavone moiety and has been shown to exhibit a broad range of biological activities. An efficient and straightforward synthetic method for generating the molecular complexity of wrightiadione was developed through three-step tandem dehydrogenation/oxidation/oxidative cyclization reactions with a Pd/Cu catalytic system. This unprecedented one-pot route utilizes a broad range of substrates, providing a convenient and powerful synthetic tool for accessing naturally occurring tetracyclic isoflavone wrightiadione and its nitrogen-containing derivatives.

Efficient synthesis of frutinone†A and its derivatives through palladium-catalyzed C - H activation/carbonylation.

Frutinone A, a biologically active ingredient of an antimicrobial herbal extract, demonstrates potent inhibitory activity towards the CYP1A2 enzyme. A three-step total synthesis of frutinone A with an overall yield of 44 % is presented. The construction of the chromone-annelated coumarin core was achieved through palladium-catalyzed CH carbonylation of 2-phenolchromones. The straightforward synthetic route allowed facile substitutions around the frutinone A core and thus rapid exploration of the structure-activity relationship (SAR) profile of the derivatives. The inhibitory activity of the synthesized frutinone A derivatives were determined for CYP1A2, and ten compounds exhibited one-to-two digit nanomolar inhibitory activity towards the CYP1A2 enzyme.

A Pd-catalyzed one-pot dehydrogenative aromatization and ortho-functionalization sequence of N-acetyl enamides.

The one-pot dehydrogenation and ortho-functionalization sequence provides access to highly functionalized arylamine-containing derivatives from readily accessible cyclic N-acetyl enamides.

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.

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.