Raquel Román

Improved Regioselectivity in Pyrazole Formation through the Use of Fluorinated Alcohols as Solvents: Synthesis and Biological Activity of Fluorinated Tebufenpyrad Analogs

The preparation of N-methylpyrazoles is usually accomplished through reaction of a suitable 1,3-diketone with methylhydrazine in ethanol as the solvent. This strategy, however, leads to the formation of regioisomeric mixtures of N-methylpyrazoles, which sometimes are difficult to separate. We have determined that the use of fluorinated alcohols such as 2,2,2-trifluoroethanol (TFE) and 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as solvents dramatically increases the regioselectivity in the pyrazole formation, and we have used this modification in a straightforward synthesis of fluorinated analogs of Tebufenpyrad with acaricide activity.

Synthesis of New Fluorinated Tebufenpyrad Analogs with Acaricidal Activity Through Regioselective Pyrazole Formation

In previous studies, our group has shown that the use of fluorinated alcohols such as trifluoroethanol (TFE) and hexafluoroisopropanol (HFIP) as solvents dramatically increases the regioselectivity in the pyrazole formation from 1,3-diketone with methylhydrazine. We have now applied this synthetic method to the preparation of new fluorinated pyrazoles, which have then been used as synthetic intermediates in the preparation of fluorinated analogs of Tebufenpyrad, a commercial acaricide. These compounds display a strong acaricidal activity that is either comparable to or better than that of the commercial compound.

Asymmetric Synthesis of Monofluorinated 1-Amino-1,2-dihydronaphthalene and 1,3-Amino Alcohol Derivatives

Enantioenriched 1-amino-4-fluoro-1,2-dihydronaphthalene derivatives are accessed via two complementary synthetic strategies. The careful optimization of the reaction conditions required for the elimination step in one route has allowed both the identification of an anchimerically assisted reaction pathway and, more importantly, access to a divergent reaction pathway toward fluorinated 1,3-amino alcohols from a common intermediate just by adjusting the number of equivalents of base used.

Asymmetric Synthesis of Fluorinated Isoindolinones through Palladium‐Catalyzed Carbonylative Amination of Enantioenriched Benzylic Carbamates

The asymmetric synthesis of fluorinated isoindolinones has been achieved by a palladium-catalyzed aminocarbonylation reaction of the corresponding α-fluoroalkyl o-iodobenzylamines. A base-mediated anti β-hydride elimination process was suggested to explain the partial erosion of the optical purity observed in some cases. This mechanistic rationale enabled the minimization of this partial racemization by fine-tuning the pKa of the base.

8-Iodonaphthalene-1-carbaldehyde: A Versatile Building Block for Diversity-Oriented Synthesis.

The scarcely studied 8-halonaphthalene-1-carbaldehyde structure has been converted into the corresponding Ellmans imine and subjected to several transformations, thus achieving an assorted library of polycyclic carbo- and heterocycles. The potential of this scaffold for Diversity-Oriented Synthesis has been shown. Most of these skeletons are unprecedented and, therefore, cover unexplored regions of the chemical space.

Fluorinated Pyrazoles and Indazoles

The synthesis of fluorine containing pyrazoles has been boosted in the past decades due to the interesting properties that confer these building blocks in pharmaceutical and agricultural active ingredients. There are two main methods for the synthesis of fluorine-containing organic compounds, namely, the direct replacement of an atom or functional group such as diazo, hydroxyl, halogen or hydrogen by fluorine, and the modification of fluorine-containing building blocks. In the case of fluorinated pyrazoles the latter approach is the most commonly applied. This chapter deals primarily with the pivotal procedures that allow the preparation of fluoro- and fluoroalkyl- pyrazoles. Their benzocondensed derivatives, indazoles, have been studied to a much lesser extent. The fundamental applications of this class of compounds in different fields are also discussed.

Homoallylic o-halobenzylamines: asymmetric diversity-oriented synthesis of benzo-fused cyclic amines

The presence of a halogen atom in the proximity of a homoallylic amine, obtained by asymmetric addition of allylzinc bromide to the corresponding tert-butyl sulfinimine, makes them versatile building blocks suitable to participate in several palladium-catalyzed processes, such as the intramolecular Heck reaction or the Sonogashira cross-coupling. The thus obtained ortho-alkynyl derivatives display two unsaturated functional groups which may be further modified by means of the intramolecular Pauson–Khand reaction or the ring-closing enyne metathesis. In this way, a variety of benzo-fused amines can be obtained in 2–3 steps from readily available starting materials.

Metal-Free and User-Friendly Regioselective Hydroxyfluorination of Olefins

A simple, user-friendly, metal-free protocol for the regioselective anti-Markovnikov hydrofluorination of olefins using readily available and inexpensive reagents has been developed. This new approach displays a broader scope than previously reported methodologies and has been applied to the late-stage fluorination of a complex molecule, giving rise to a fluorosteroid derivative. The stereochemistry of the process has also been studied in some detail.

Efficacy and activity prediction by molecular topology of new drugs against the Tetranychus urticae plague.

Tetranychus urticae Koch is an important pest affecting citrus, for which biological control has not yet been achieved; therefore, acaricides are commonly used instead. The goal of the work reported in this paper was to measure the efficacy of different new compounds--uracil derivatives--on this mite and conduct a quantitative structure-activity relationship (QSAR) study based on the results obtained, in order to set up a model capable of predicting the acaricidal activity of further new compounds. Some of the tested new products proved highly effective against T. urticae. Besides, topological indices were used as structural descriptors. The result was a topological model consisting of two discriminant functions for distinguishing between active and inactive compounds, and a predictive equation for the adult mortality percentage on the sixth day. This model was then sequentially applied to a large database of compounds with unknown activity against the Tetranychus urticae plague. Finally, a preliminary toxicity study of the most effective novel compounds supports their non-toxicity, performing even better than commercial referents.