Mercedes Villacampa

Ultrasound assisted Diels-Alder reactions of 1-azadienes with normal electronic demand

Abstract Ultrasound irradiation accelerates hetero Diels-Alder reactions between 1-dimethylamino-1-azadienes and electron-defficient dienophiles. Besides the lower reaction times and increased yields, other advantages of the sonicated reactions are the possibility of isolating previously unknown adducts due to the milder reaction conditions and, in some cases, the decrease in side reactions.

Mild and General Synthesis of Pyrrolo[2,1-a]isoquinolines and Related Polyheterocyclic Frameworks from Pyrrole Precursors Derived from a Mechanochemical Multicomponent Reaction

The combination of a three-component, solvent-free pyrrole synthesis performed under mechanochemical conditions with a TMSOTf-catalyzed oxonium-mediated cyclization gave general access to pyrrolo[2,1-a]isoquinoline derivatives under very mild conditions. The structural diversity generated by this method was extended by the preparation of six additional unusual polyheterocyclic frameworks.

Regioselective synthesis of 1,8-diazaanthracene-9,10-dione by tandem directed ortho-metallation/metal-halogen exchange

Abstract Tandem directed ortho-metallation/metal-halogen exchange reactions between N,N-diethyl-pyridine-2-carboxamide and 2-bromopyridine-3-carbaldehyde yield 1,8-diazaanthracene-9,10-dione. This compound has been further functionalized to its N-oxide and the corresponding 2,9,10-trione derivative, structurally related to the antibiotic diazaquinomycin A.

Concise synthesis of atorvastatin lactone under high-speed vibration milling conditions

The Hantzsch-type sequential three-component reaction under high-speed vibration milling conditions between 4-methyl-3-oxo-N-phenylpentanamide, tert-butyl 2-[(4R,6R)-6-(2-aminoethyl)-2,2-dimethyl-1,3-dioxan-4-yl]acetate and 1-(4-fluorophenyl)-2-iodo-2-phenylethanone in the presence of ytterbium triflate and silver nitrate, followed by hydrolytic deprotection/lactonization, afforded atorvastatin lactone in 38% overall yield, thus providing ready access to the top-selling antihyperlipidemic drug atorvastatin calcium.

Vinylation of nitro-substituted indoles, quinolinones, and anilides with grignard reagents.

The reaction of vinyl Grignard reagents with o-methoxynitroarenes containing an electron-releasing substituent para to the nitro group proceeds through a pathway that is different from the initially expected Bartoli indole synthesis. Thus, instead of giving fused indole derivatives, these reactions provide a very mild and efficient new procedure for the synthesis of synthetically relevant aromatic systems containing an o-nitrovinyl moiety, such as 5-nitro-4-vinylindoles, 6-nitro-7-vinylindoles, 6-nitro-5-vinyl-2(1H)quinolinones, and 4-nitro-3-vinylanilines.

New findings on the Vilsmeier-Haack approach to quinoline derivatives

Abstract The presence of electron-releasing substituents on the aromatic ring of anilides, although necessary for the Vilsmeier-Haack cyclization to quinolines to proceed efficiently, can cause failure of the expected cyclization, leading to (Z) N,N-dimethylformamidines through an alternative course. A similar behaviour is observed when π-donor groups are introduced on the α position of the anilide, although in this case some cyclization to quinoline derivatives generally occurs.

Three-component access to 2-pyrrolin-5-ones and their use in target-oriented and diversity-oriented synthesis

The Hantzsch-type microwave-assisted, solvent-free sequential three-component reaction between primary amines, β-dicarbonyl compounds and α-bromoesters in the presence of indium trichloride afforded 2-pyrrolin-5-ones, which are difficult to access by alternative methods. Ready access to these compounds allowed their use as synthetic building blocks in a target-oriented project aimed at the synthesis of a compound that had previously been postulated as a candidate for HIV integrase inhibition on the basis of computational studies. The versatility of 2-pyrrolin-5-ones was further verified by their use in a diversity-oriented synthesis context, leading to a library of highly functionalized bispiro compounds. The overall process leading to these compounds involved the generation of six bonds and two cycles over three steps, two of which are multicomponent, and the fully controlled generation of up to four stereocenters, including two quaternary ones.

Synthesis and stereochemistry of tropane 6-spiro-hydantoins

The synthesis of several representatives of the previously unknown N-alkyl-nortropane-6-spirohydantoin ring system by Bucherer-Bergs reaction of 8-alkyl-8-azabicyclo[3.2.1]octan-6-ones is described. 3-Oxo derivarives of the parent structure were also prepared. The stereochemical outcome of the Bucherer-Bergs reaction is discussed on the basis of 1 H-nmr and 13 C-nmr data

High-speed vibration-milling-promoted synthesis of symmetrical frameworks containing two or three pyrrole units

The pseudo-five-component reaction between β-dicarbonyl compounds (2 molecules), diamines and α-iodoketones (2 molecules), prepared in situ from aryl ketones, was performed efficiently under mechanochemical conditions involving high-speed vibration milling with a single zirconium oxide ball. This reaction afforded symmetrical frameworks containing two pyrrole or fused pyrrole units joined by a spacer, which are of interest in the exploration of chemical space for drug discovery purposes. The method was also extended to the synthesis of one compound containing three identical pyrrole fragments via a pseudo-seven-component reaction. Access to compounds having a double bond in their spacer chain was achieved by a different approach involving the homodimerization of 1-allyl- or 1-homoallylpyrroles by application of cross-metathesis chemistry.