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Abstract: Metabolic syndrome, an increasing problem in western society, is a cluster of conditions that affect cardiovascular health, lipid and glucose management, increasing the risk of heart diseases, stroke and diabetes. Bioactive flavonoids are a great resource of compounds with proven antiinflammatory activities. Naringin, a natural flavanone found in citrus fruits, and its aglycone have demonstrated to ameliorate obesity, dyslipidemia, and insulin resistance in animal models. The principal mechanisms by which these flavonoids exert their action involve AMPK and PPARα up-regulation and the down-regulation of genes involved in lipid metabolism. Although different studies have been carried out to define the pharmacological effects of these flavonoids, their therapeutic use is still limited.

Fluoromethyl groups possess specific steric and electronic properties and serve as a bioisostere of alcohol, thiol, nitro, and other functional groups, which are important in an assortment of molecular recognition processes. Herein we report a catalytic method for the asymmetric synthesis of a variety of enantioenriched products bearing fluoromethylated stereocenters with excellent yields and enantioselectivities. Various N,P-ligands were designed and applied in the hydrogenation of fluoromethylated olefins and vinyl fluorides.

We present a highly efficient convergent asymmetric hydrogenation of E/Z mixtures of enamides catalyzed by N,P–iridium complexes supported by mechanistic studies. It was found that reduction of the olefinic isomers (E and Z geometries) produces chiral amides with the same absolute configuration (enantioconvergent hydrogenation). This allowed the hydrogenation of a wide range of E/Z mixtures of trisubstituted enamides with excellent enantioselectivity (up to 99% ee). A detailed mechanistic study using deuterium labeling and kinetic experiments revealed two different pathways for the observed enantioconvergence. For α-aryl enamides, fast isomerization of the double bond takes place, and the overall process results in kinetic resolution of the two isomers. For α-alkyl enamides, no double bond isomerization is detected, and competition experiments suggested that substrate chelation is responsible for the enantioconvergent stereochemical outcome. DFT calculations were performed to predict the correct absolute configuration of the products and strengthen the proposed mechanism of the iridium-catalyzed isomerization pathway.

The catalytic asymmetric hydrogenation of olefins constitutes a powerful method for the preparation of chiral compounds. A series of prochiral unsaturated amides were efficiently reduced with high enantioselectivities by means of an iridium N,P-complex-catalyzed hydrogenation. Its application in the synthesis of fenpropidin and the possibility of using isomeric mixtures of starting materials are attractive features of the method.

Enantioconvergent catalysis has the potential to convert different isomers of a starting material to a single highly enantioenriched product. Here we report a novel enantioselective double convergent 1,3-rearrangement/hydrogenation of allylic alcohols using an Ir-N,P catalyst. A variety of allylic alcohols, each consisting of a 1:1:1:1 mixture of four isomers, were converted to the corresponding tertiary alcohols with two contiguous stereogenic centers, in up to 99%