Effect of Microwave Irradiation on the Fries Rearrangement Reactions of Acetyloxy- and Benzoyloxybenzenes

The Fries rearrangement reactions of acetyloxy- and benzoyloxybenzenes were carried out both under microwave irradiation and conventional heating conditions, and the effect of microwave irradiation was examined. Acceleration of the reaction for the acetyloxy derivatives could not be confirmed, but was successfully demonstrated for the benzoyloxy derivatives. On the Fries rearrangement, the Lewis acid coordinates to the ester oxygens, but also coordinates to the aromatic rings. The microwave is efficiently absorbed by such an adduct between the Lewis acid and substrate, resulting in acceleration of the reaction.

Programmed multiple C–H bond functionalisation of the privileged 4-hydroxyquinoline template

<div> <p>The introduction of substituents on bare heterocyclic scaffolds can selectively be achieved by directed C–H functionalisation. However, such methods have only occasionally been used, in an iterative manner, to decorate various positions of a medicinal scaffold to build chemical libraries. We herein report the multiple, site selective, metal-catalyzed C–H functionalisation of a "programmed" 4-hydroxyquinoline. This medicinally privileged template indeed possesses multiple reactive sites for diversity-oriented functionalisation, of which four were targeted. The C-2 and C-8 decorations were directed by an <i>N</i>-oxide, before taking benefit of an O-carbamoyl protection at C-4 to perform a Fries rearrangement and install a carboxamide at C-3. This also released the carbonyl group of 4-quinolones, the ultimate directing group to functionalise position 5. Our study highlights the power of multiple C–H functionalisation to generate diversity in a biologically relevant library, after showing its strong antimalarial potential.</p></div>

Programmed multiple C–H bond functionalisation of the privileged 4-hydroxyquinoline template

<div> <p>The introduction of substituents on bare heterocyclic scaffolds can selectively be achieved by directed C–H functionalisation. However, such methods have only occasionally been used, in an iterative manner, to decorate various positions of a medicinal scaffold to build chemical libraries. We herein report the multiple, site selective, metal-catalyzed C–H functionalisation of a "programmed" 4-hydroxyquinoline. This medicinally privileged template indeed possesses multiple reactive sites for diversity-oriented functionalisation, of which four were targeted. The C-2 and C-8 decorations were directed by an <i>N</i>-oxide, before taking benefit of an O-carbamoyl protection at C-4 to perform a Fries rearrangement and install a carboxamide at C-3. This also released the carbonyl group of 4-quinolones, the ultimate directing group to functionalise position 5. Our study highlights the power of multiple C–H functionalisation to generate diversity in a biologically relevant library, after showing its strong antimalarial potential.</p></div>

The Programmed Multiple C–H Bond Functionalization of 4-Hydroxyquinoline and Its Medicinal Potential

<p>The introduction of substituents on bare heterocyclic scaffolds can selectively be achieved by directed C–H functionalization. However, such methods have only occasionally been used, in an iterative manner, to decorate various positions of a medicinal scaffold to build chemical libraries. We herein report the multiple, site selective, metal-catalyzed C–H functionalization of a "programmed" 4-hydroxyquinoline. This medicinally privileged template indeed possesses multiple reactive sites for diversity-oriented functionalization, of which four were targeted. The C-2 and C-8 decorations were directed by an <i>N</i>-oxide, before taking benefit of an <i>O</i>-carbamoyl protection at C-4 to perform a Fries rearrangement and install a carboxamide at C-3. This also released the carbonyl group of 4-quinolones, the ultimate directing group to functionalize position 5. Our study highlights the power of multiple C–H functionalization to generate diversity in a biologically relevant library, after showing its strong antimalarial potential.</p>