María-Paz Cabal

Tosylhydrazide-promoted palladium-catalyzed reaction of β-aminoketones with o-dihaloarenes: combining organocatalysis and transition-metal catalysis.

One of the main challenges of current organic synthesis is the design of practically simple and increasingly efficient organic transformations. The sequential formation of various bonds through tandem or cascade reactions constitutes one approach to achieving this goal. In these types of reactions, high molecular complexity can be built from relatively simple starting materials in a single synthetic operation. Moreover, among the advantages of these processes are atom, solvent, and catalyst economy and operational simplicity, as isolation of intermediates is avoided. In the context of transition-metal-catalyzed reactions, processes in which a single, multifunctional metal catalyst promotes various individual reactions (auto-tandem catalysis) are of great interest. By taking advantage of the wide scope, high performance, and remarkable stability of state-ofthe-art Pd catalysts, a variety of Pd-catalyzed processes have been developed based on this principle. We have recently discovered a new Pd-catalyzed C C bond-forming reaction that employs N-tosylhydrazones as nucleophilic component in a new type of “stoichiometric organometallic-free” cross-coupling process. Moreover, the tosylhydrazone can be generated in situ from a carbonyl compound and tosylhydrazide, which implies that the carbonyl compounds can be directly employed in the crosscoupling reaction (Scheme 1). Following our interest in auto-tandem Pd-catalyzed processes, we decided to investigate whether the new C C bond-forming reaction with tosylhydrazones could be one of the processes promoted by a multifunctional catalyst. Following this idea, we designed a possible sequence employing hydrazones derived from b-aminoketones I and odihalobenzene derivatives II as starting materials. Thus, in the presence of the Pd catalyst two consecutive processes might occur: a C C cross-coupling reaction (arylation) to give intermediate III, followed by an intramolecular C N bondforming reaction (amination) affording substituted tetrahydroquinolines IV (Scheme 2). Moreover, taking into account that a variety of b-aminoketones are accessible in enantiomerically pure form through asymmetric organocatalyzed Mannich reactions, our ultimate goal would be to develop a heterocyclization process that would preserve the configurationally unstable stereogenic center in the a position to the carbonyl group.

Enamines in solid-phase: synthesis and reactivity towards electrophiles

Abstract Enamines are synthesized in solid-phase by amination of terminal acetylenes with a secondary amine attached to Wang resin in a process catalyzed by mercury(II) acetate. The enamines obtained react with electrophiles such as isocyanates and nitroolefins to give rise to the expected addition products, which can be released from the resin by hydrolysis of the enamine under mild acidic conditions.

Synthesis of 1,1-Disubstituted Indenes and Dihydronaphthalenes through C–C/C–C Bond-Forming Pd-Catalyzed Autotandem Reactions

A novel synthesis of 1,1-disubstituted 1H-indenes is described involving the Pd-catalyzed cascade reaction between o-bromophenyl-β-bromostyrenes and N-tosylhydrazones in a process comprising the consecutive formation of two Csp3-C bonds on the same carbon atom: the cross-coupling of the N-tosylhydrazone with the alkenyl bromide and the intramolecular Heck reaction on the newly formed double bond. A similar approach has been applied to the preparation of 1,1-disubstituted naphthalenes.

A new 2-aminobuta-1,3-diene derivative and its utility as a building block in hetero- and carbo-cyclization processes

2-Morpholinobuta-1,3-diene cycloadds to aromatic aldehydes, N-benzylideneaniline, and methyl vinyl ketone, to give oxan-4-ones, 4-morpholinotetrahydropyridines, and 4-acetyl-1-morpholinocyclohexene derivatives, respectively, with a high degree of diastereoselectivity.

Substituent effects on the reactivity of 2-morpholinobutadienes in the presence of dienophiles

2-Morpholinobutadienes (1) behave like typical enamines in their reactions with dimethyl acetylenedicarboxylate (2), β-nitrostyrene (3), diethyl 2-oxomalonate (4), and benzaldehyde (5). The nature of the resulting products is strongly dependent on the conformation which the 2-aminobutadienes (1) can adopt, as a function of the substituents. Only when the substituents can participate in the course of the reaction may the 2-morpholinobutadienes behave like a 4π-system in a concerted process.

Strong In Vitro Activities of Two New Rifabutin Analogs against Multidrug-Resistant Mycobacterium tuberculosis

ABSTRACT Two new rifabutin analogs, RFA-1 and RFA-2, show high in vitro antimycobacterial activities against Mycobacterium tuberculosis. MIC values of RFA-1 and RFA-2 were ≤0.02 μg/ml against rifamycin-susceptible strains and 0.5 μg/ml against a wide selection of multidrug-resistant strains, compared to ≥50 μg/ml for rifampin and 10 μg/ml for rifabutin. Molecular dynamic studies indicate that the compounds may exert tighter binding to mutants of RNA polymerase that have adapted to the rifamycins.

Synthesis of 1-aza-1,3-dienes and 2-morpholino-1,3-dienes via catalytic aminomercuriation of alk-3-en-1-ynes

Under specific reaction conditions only the terminal Ctriple bond of several alk-3-en-1-ynes adds amines, via catalytic aminomercuriation, to afford 1-aza- and 2-morpholino-1,3-dienes.