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La tesis doctoral describe estrategias útiles y sencillas para las síntesis de 2-oxindoles 3,3'-disustituídos y alcoholes homoalílicos. La memoria se divide en dos grandes bloques: el primero referido a la alquilación desacilativa como método para la síntesis de 2-oxindoles 3,3'-disustituídos que engloba la introducción I, el capítulo I titulado alquilación desacilativa para la síntesis de 2-oxindoles 3,3'-disustituídos y capítulo II titulado bromación desacilativa para la síntesis de 3,3'-bioxindoles y aislamiento de 3-bromooxindoles. La segunda parte se refiere a fotocatálisis y metalofotocatálisis como nuevos métodos de síntesis orgánica y engloba la introducción II, capítulo III titulado fotocatálisis para la síntesis de 3,3'-bioxindoles y capítulo IV titulado catálisis dual para la alilación de aldehídos.

The Suzuki-Miyaura cross-coupling reaction using 4-amino-1,2,4-triazoles and 1,3,4-oxadiazoles-2-thiones·palladium (II) is studied. The reaction is optimized and the most appropriate catalytic complex is tested with several aryl halides, boronic acids in an environmentally benign solvent system (H2O/EtOH). The recovery of the catalytic species is also surveyed because of the nature of the employed solvent. A domino process is efficiently carried out following the standard conditions. Several surface parameters of the ligands are analyzed and the resulting values are extrapolated to the insoluble palladium catalyst.

The synthesis of 3,3'‐bioxindoles employing deacylative alkylations (DaA) in one‐pot process, where the 3‐bromooxindoles are generated in situ, is described. Good yields and moderate diastereoselections are obtained. By the modification of this procedure the synthesis of pure 3‐bromooxindoles through a deacylative bromination (DaB) is achieved. These bromides are efficiently employed in a photoredox dimerization process to get the desired 3,3'‐bioxindoles in good yields and low diastereoselections. In this single‐electron‐transfer (SET) mechanism the presence of a high quantum‐yield iridium(III) complex ensures high conversions in short reaction times.

Two 4-amino-1,2,4-triazoles and two 1,3,4-oxadiazoles are obtained in a common synthetic route including hydrogenation-hydrazidation of (Z)-methyl octadec-9-enoate to octadecanoic hydrazide under atmospheric air. Preservation of olefinic bond in heptadec-8-enyl group is achieved by carrying out hydrazidation reaction under the presence of an argon atmosphere. The disappearance of the olefinic bond is detected by physical data, IR, 1H, and13C NMR spectroscopy. New palladium complexes derived from 4-amino-5-heptadecyl-1,2,4-triazole-3-thiol and 5-heptadecyl-1,3,4-oxadiazole-2(3H)-thione are obtained and characterized by elemental analysis (solid state), IR, 1H, 13C NMR spectroscopy, XRD, and XPS. These resulting metallic entities are also identified in solution based in mass spectrometry (MS-ESI) experiments. Most compounds and their palladium(II) complexes are tested in vitro against Gram-positive, Gram-negative bacteria, and fungi, some of them showed variable activity.

The synthesis of 3,3'‐bioxindoles employing deacylative alkylations (DaA) in one‐pot process, where the 3‐bromooxindoles are generated in situ, is described. Good yields and moderate diastereoselections are obtained. By the modification of this procedure the synthesis of pure 3‐bromooxindoles through a deacylative bromination (DaB) is achieved. These bromides are efficiently employed in a photoredox dimerization process to get the desired 3,3'‐bioxindoles in good yields and low diastereoselections. In this single‐electron‐transfer (SET) mechanism the presence of a high quantum‐yield iridium(III) complex ensures high conversions in short reaction times.

The synthesis of palladium complexes derived from 4-amino-3-pentadecyl-3H-1,2,4-triazole-3-thiones and 3-pentadecyl-1,3,4-oxadiazole-2(3H)-thiones are reported. They were obtained from palladium acetate and dipotassium tetrachloropalladate(II) and their composition was assigned by elemental analysis (solid state). The resulting metallic entities were also characterized in solution based in mass spectrometry experiments. Their application in organic synthesis as cross-coupling reaction catalysts is described. One example of both conventional Tsuji–Trost and Mizoroki–Heck reactions were efficiently carried out in very high chemical yield.

Herein we introduce the recent developments of a new strategy based on deacylative alkylation (DaA) reactions for the generation of quaternary stereocenters based on the in situ preparation and functionalization of enolates under very mild reaction conditions. Palladium‐catalyzed deacylative allylation and benzylation reactions of carbon nucleophiles are performed with the corresponding alcohols. This methodology has been applied to the synthesis of the calcium ion channel blocker verapamil, the antiviral (+)‐hamigeran B, several oxindole precursors of esermethole, horsfiline, physostigmine, phenserine, meso‐folicanthine, meso‐chinonanthine and the dimer cyclotriptamine alkaloids. Base‐promoted deacylative reactions enable the functionalization of 2‐oxindole enolates at the 3‐position with alkyl halides and electrophilic alkenes. In the presence of oxygen or air, 3‐hydroxy‐2‐oxindoles are prepared by deacylative oxidation. Detrifluoroacylative reactions are promoted by a base generating fluoroenolates, which can participate in aldol, Mannich and Michael reactions for the preparation of important fluorinated intermediates. Finally, palladium‐catalyzed deacylative cross‐coupling of acetyl diazoacetates and phosphonates with aryl iodides let to the formation of aryl diazoacetates and phosphonates, respectively. The same process, with 2‐iodoazoarenes and 2‐iodoaryltriazenes, gives 2H‐indazoles, which are important pharmacophores.

The synthesis of 3,3-disubstituted N-methyloxindoles, starting from 3-acetyl-2-hydroxy-1-methyloxindole employing a sequential one-pot synthesis, is studied. The process involves a first alkylation in the presence of 1 equiv. of both organic halide and Triton B and the second one employs another 1.5 equiv. of each in moderate to high yields. This procedure is compared with the results obtained from the direct dialkylation of N-methyloxindole. The metathesis of one of the corresponding diallylated product was also studied obtaining the spiranic oxindole. All these methodologies are directed towards the access to anticancer agents and natural biologically active products.

An innovative and efficient monoalkylation and nonsymmetrical 3,3-dialkylation of oxindoles has been achieved. First, the monoalkylation of 3-acetyl-2-oxindoles can be performed in good yields under mild reaction conditions using alkyl halides and benzyltrimethylammonium hydroxide (Triton B) as base at room temperature. This methodology is applied to construct the synthetically challenging compound 1,3-dimethyl-2-oxindole. Subsequent deacylative alkylation (DaA) of the alkylated 3-acetyl-2-oxindoles with alkyl halides takes place efficiently using LiOEt or by conjugate addition with electron-deficient alkenes in the presence of Triton B at room temperature under argon, affording the corresponding unsymmetrically 3,3-disubstituted 2-oxindoles. This simple methodology has been applied to the synthesis of precursors of horsfiline, esermethole, physostigmine, and phenserine alkaloids.