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In this review, we explore the applications of Asymmetric Hydrogenation (AH) and Asymmetric Transfer Hydrogenation (ATH) in the total synthesis of natural flavonoids and their analogues, highlighting the limitations and opportunities in the field.

The oxo-tethered-Ru(II) precatalyst promoted the one-pot C═C/C═O reduction of chalcones using sodium formate as the hydrogen source in water through asymmetric transfer hydrogenation. Twenty-seven 1,3-diarylpropan-1-ols were obtained in good to excellent yields (up to 96%) and enantiomeric purities (up to 98:2). Our data suggested that the enones are first reduced to the corresponding dihydrochalcones (1,4-selectivity) and then into 1,3-diarylpropan-1-ols (C═O reduction). The stereoelectronic effects of electron-donating and electron-withdrawing groups at the

3-Arylidenechroman-4-ones and 2-arylidene-1-tetralones are hydrogenated to cis-benzylic alcohols in dr's and er's up to 99:1 via a C═C and C═O one-pot reduction in the presence of 2-5 mol % Noyori-Ikariya-type RuII chiral complexes and HCO2Na as a hydrogen source under asymmetric transfer hydrogenation-dynamic kinetic resolution (ATH-DKR) conditions. The oxidation of theses substrates resulted in the enantioselective synthesis of the natural homoisoflavanone dihydrobonducellin and its carba-analogues.

Morita-Baylis-Hillman adducts (MBHA) is a class of polyfunctional molecules that has been standing out due to their versatility and expressive biological activities. Therefore, this paper describes the synthesis and antiproliferative activity of some new MBHA/7-choroquinoline hybrids. The Michael acceptors were obtained starting from 4,7-dichloroquinoline which were submitted to the Morita-Baylis-Hillman reaction with ortho, meta and para-nitrobenzaldehyde. The in vitro screening of the synthetized MBHA against NCI-H292, HCT-116 and MCF-7 cancer cells suggests the influence of the spacer chain in its inhibition potential. The 50% inhibitory concentration (IC50) obtained in the antiproliferative assay using MCF-7, HCT-116, HL-60 and NCI-H292 cancer cells indicate expressive cytotoxic potential of the adducts containing nitro group in the ortho position, with IC50 of 4.60 µmol L-1. MBHA/7-choroquinoline hybrids were more active than MBHA described in literature, indicating the improvement of the cytotoxic effect due to 7-chloroquinoline moiety in the molecular structure, with maximum selectivity index values of 11.89.

Herein we describe the design, synthesis and structural characterization by NMR and X-ray of new molecular hybrids 4a - 4c containing the nitroaromatic MBHA moiety and the 7-chloroquinoline pharmacophores, linked by an aliphatic spacer as a model for antiprotozoal drugs. Firstly, the 4,7-dichloroquinoline ( 7 ) reacted with excess of ethylene glycol, through a SNAr promoted by t -BuOK, to prepare the 2-(7-chloroquinolin-4-yloxy)ethanol ( 6 ) in 98% isolated yield. Then, the novel 2-(7-chloroquinolin-4-yloxy) ethyl acrylate ( 5 ) was synthesized in 78% isolated yield by reacting the alcohol ( 6 ) with acryloyl chloride and TEA in CH 2 Cl 2 . Finally, this acrylate ( 5 ) reacted with o -nitrobenzaldehyde, m -nitrobenzaldehyde and p -nitrobenzaldehyde through Morita-Baylis-Hillman reactions promoted by DABCO at room temperature, using t -BuOH:Water (9:1) as solvent, to afford the new hybrids 4a-4c in 73–76% isolated yields. Three-dimensional structures were characterized in both monomeric and intermolecular packing by X-Ray experiments.

Catalytic enantioselective 1,3-dipolar cycloaddition between imino esters and electrophilic alkenes, employing chiral metal complexes derived from copper(I) and silver(I) salts and (S)-DM- or (S)-DTBM-Segphos as ligands produces diastereodivergently exo- or endo-cycloadducts, respectively. The effect of the functional group of the dipolarophile and the fine tuning of the catalyst plays an important role in promoting reverse diastereoselectivities. The origins of experimentally observed enantioselectivity and diastereoselectivity data, as well as the origin of the observed switched endo/exo ratios, are also explained by means of density functional theory calculations. The authors gratefully acknowledge the financial support from CAPES (Brazil), the Spanish Ministerio de Ciencia, Innovación y Universidades (projects CTQ2013-43446-P, CTQ2016-81893REDT and CTQ2014-51912-REDC), the Spanish Ministerio de Economía, Industria y Competitividad, Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER, EU) (projects CTQ2016-76782-P, CTQ2016-80375-P and CTQ2016-81797-REDC), the Generalitat Valenciana (PROMETEOII/2014/017), the Gobierno Vasco/Eusko Jaurlaritza (GV/EJ, Grant IT673-13), and the University of Alicante. G.S.C. acknowledges CAPES (Brazil) for the fellowship (Process CSF-PVE-S-88887.127574/2016-00). O.L. gratefully acknowledges UPV/EHU for her postdoctoral grant.

4-(Trifluoromethyl)-2(1H)-pyrimidinones were synthesized from the reaction between 1,1,1-trifluoro-4-methoxy-3-buten-2-ones [CF3C(O)C(R2)C(R1)(OCH3) where R1 = Ph, 4-F-C6H4, 4-Cl-C6H4, 4-Br-C6H4, 4-I-C6H4, 4-CH3-C6H4, naphth-2-yl, 4-OCH3-C6H4, thien-2-yl and R2 = H, CH3] and urea in the presence of ionic liquid [BMIM][BF4] combined with HCl. The results demonstrate that [BMIM][BF4]/HCl catalyzed the reaction in the absence of molecular solvents. Use of ionic liquid combined with HCl allowed the reaction temperatures to be increased to 100 °C and decreased the reaction times from 48–72 to 3–6 h. The products were obtained in good yields (70–97 %).

In this work, 3-haloacetyl-4-methylquinolines were synthesized from the reaction of 4-alkoxy-3-alken-2-ones [R¹C(O)CH=C(R²)OCH3, where R¹ = CF3, CCl3, CHCl2, CF2Cl, CF2CF3 and R² = Me, Et, Pr, Bu, i-Bu and i-Pe] and 2-aminoacetophenone. The reaction was performed in ionic liquid and 4-toluene sulfonic acid under microwave irradiation. Results showed that the catalytic method was effective. Products were formed in a short time (10-20 min) and presented good yields (70-91%). Neste trabalho, 3-haloacetil-4-metilquinolinas foram sintetizadas a partir da reação de 4-alcóxi-3-alquen-2-onas [R¹C(O)CH=C(R²)OCH3, onde R¹ = CF3, CCl3, CHCl2, CF2Cl e CF2CF3 e R² = Me, Et, Pr, Bu, i-Bu e i-Pe] e 2-aminoacetofenona. A reação foi realizada em líquido iônico e ácido 4-toluenosolfônico sob irradiação de micro-ondas. Os resultados mostraram que o método catalítico foi efetivo e os produtos foram formados em tempos de reação curtos (10-20 min) e com bons rendimentos (70-91%).

The crystalline structure of five 3-(R3) and/or 5-(R5)-substituted 7-trichloromethyl-2-methylpyrazolo[1,5-a]pyrimidines [where R3, R5 = H, Pr (1); Br, H (2); Br, Me (3); H, H (4); and H, Me (5)] were studied from X-ray diffractometry data. It was found that compounds presented themselves as main intermolecular interactions: Cl⋯Cl (1), Br⋯Cl (2,3); and Cl⋯N-pyrimidine (4,5). In compounds 1–3, other interactions reinforce the stabilization of the crystal structure, such as C–H⋯N-pyrimidine (1,2) Cl⋯π-pyrazole (1); C–Br⋯π-pyrimidine (2); and pyrazole-π⋯π-pyrimidine, pyrimidine-π⋯π-pyrimidine (3). This study shows that the Cl⋯N-pyrimidine interactions present in compounds 4 and 5 are a typical halogen⋯base Lewis interaction. Geometric information of Cl⋯Br and Cl⋯Cl interactions could be explained by the σ-hole concept. In compound 2, the chlorine atom participates with its σ-hole, while in compound 3, the σ-hole of the interaction comes from the bromine atom. The Cl⋯π-pyrazole and Br⋯π-pyrimidine interactions have a different nature; while the Br⋯π-pyrimidine interaction is a strong lone pair⋯π interaction, the Cl⋯π-pyrazole is a new interaction: σ-hole⋯π.

Title compounds are synthesized in high yields from butenones (I) and urea in short reaction times compared to other known methods.