Postmodification of voxelotor (GBT 440) via [Rh]-catalyzed cross dehydrogenative coupling with olefins.

The directed Rh(III)-catalyzed cross dehydrogenative coupling of the pyrazole unit of the GBT-440 scaffold has been explored with simple as well as conjugated olefins to synthesize post-functionalized GBT-440 analogues. The screening of these synthesized compounds for improving the oxygen binding efficiency of the hemoglobin isolated from the sickled red blood cells revealed that some of these compounds are as good as GBT-440.

Iridium(III)-Catalyzed Alkynylation of 2-(Hetero)arylquinazolin-4-one Scaffolds via C-H Bond Activation.

The directed C-H alkynylation of 2-(hetero)arylquinazolin-4-ones has been explored with the ethynylbenziodoxolone reagent TIPS-EBX employing an Ir(III) catalyst. Complementary conditions for either monoalkynylation or dialkynylation have been developed. Also demonstrated is the broad scope of this reaction and the compatibility of various functional groups such as -F, -Cl, -Br, -CF3, -OMe, -NO2, and alkyl, etc.

I2-mediated regioselective C-3 azidation of indoles.

An unprecedented synthesis of novel 3-azido indoles has been developed using I2 and NaN3 in high yields and excellent regioselectivity. The reaction proceeds under metal-free conditions at room temperature. Essentially, an umpolung in reactivity at the C-3 position of indole has been achieved by the activation of indoles with I2.

Oxidative Rearrangement of Stilbenes to 2,2-Diaryl-2-hydroxyacetaldehydes.

A one-pot oxone-mediated/iodine-catalyzed oxidative rearrangement of stilbenes leading to 2,2-diaryl-2-hydroxyacetaldehydes is described. Control experiments revealed that a 2,2-diarylacetaldehyde was initially formed that undergoes subsequent α-hydroxylation. The resulting α-hydroxyaldehydes have been subjected to a one-pot Still-Gennari olefination followed by cyclization, leading to 5,5-diaryl-γ-butenolides.