Juan Ignacio Padrón

This work delves into the reactivity of olefins with iron(III) salts and the methodologies derived from these transformations. From simple, unactivated olefins, where we present the introduction of novel strategies to control Markovnikov and anti-Markovnikov selectivity, to an expansive discussion about systems bearing increasingly complex functional groups, we highlight approaches for achieving stereocontrolled and directed synthesis toward valuable scaffolds such as oxa – and aza-heterocycles; their application to natural product synthesis is also analyzed as well.

A TMSOTf-mediated diastereoselective methodology was developed to access mono- and bicyclic Δ ³ -vinyltriflated disubstituted 2,7- cis -oxepenes via an alkyne-Prins cyclisation.

The way that aromatic ligands arrange themselves around metal ions can be influenced by the hydrophobic effects caused by water.

This work presents a new binaphthyl phosphate scaffold with a first-row transition metal, copper(ii), and its outstanding luminescence properties.

A series of new hybrid compounds was prepared combining tetrahydropyran rings with different aromatic systems by means of a 1,2,3‐triazole, using a building block strategy. The design of these structures was guided by Lead‐Likeness and Molecular Analysis (LLAMA) software, adding modifications to our most potent scaffold (the tetrahydropyran ring) to generate promising “lead‐like” candidates, which were subsequently compared against reported anticancer compounds. Our synthesized compounds demonstrated significant antiproliferative activity when compared with the standards cisplatin and 5‐fluorouracil, across a panel of six different tumor cell lines. Moreover, compared with our group's previous hybrid compounds, these new structures exhibit similar activity while offering simpler synthesis and greater potential for structural diversification, a fact that was previously an issue. Further investigations on the most active compounds included assessments of reproductive cell survival, inhibition of cell migration, and effects on nuclear morphology, indicating potential diverse mechanisms of action for these compounds. Pharmacokinetic properties were also calculated for the whole series of compounds using the pkCSM online software.

The physical factors governing the catalysis in Lewis acid-promoted carbonyl-ene reactions have been explored in detail quantum chemically. It is found that the binding of a Lewis acid to the carbonyl group directly involved in the transformation greatly accelerates the reaction by decreasing the corresponding activation barrier up to 25 kcal/mol. The Lewis acid makes the process much more asynchronous and the corresponding transition state less in-plane aromatic. The remarkable acceleration induced by the catalyst is ascribed, by means of the activation strain model and the energy decomposition analysis methods, mainly to a significant reduction of the Pauli repulsion between the key occupied π-molecular orbitals of the reactants and not to the widely accepted stabilization of the LUMO of the enophile.

A new methodology for the synthesis of seven membered unsaturated azacycles (tetrahydroazepines) was developed. It is based on the powerful aza-Prins cyclization in combination with the Peterson-type elimination reaction. In a single reaction step, a C-N, C-C bond and an endocyclic double bond are formed. Under mild reaction conditions and using iron(III) salts as sustainable catalysts, tetrahydroazepines with different degrees of substitution are obtained directly and efficiently. DFT calculations supported the proposed mechanism.

A series of triazole linked tetrahydropyran–oxazole hybrids was synthesized based on a previously reported lead compound with selective antiproliferative activity against human tumour cell lines. The series was prepared to evaluate the impact of LogP and different modifications in the activity, and the new compounds were assayed against A549, HBL‐100, HeLa, SW1573, T‐47D, and WiDr cell lines. Also, the potentiality to be P‐gp substrate was tested. The compounds exhibited good antiproliferative results when compared with the standards cisplatin and 5‐fluorouracil. In silico studies to evaluate pharmacokinetic properties using pkCSM software were also carried out.

A direct, catalytic, and complementary method to obtain 2-substituted homoallyl sulfonyl amides is described, starting from sulfonyl amides, aldehydes, and allyltrimethylsilane using iron(III) chloride as a sustainable catalyst. The scope of the process and the reactivity in aza-Prins cyclization is evaluated and supported by density functional theory (DFT) studies. Finally, an evaluation of the antiproliferative activity for this family of sulfonyl amides is also included.