RESUMEN
The synthesis of functionalized 1-tetralones by the rhodium(i)-catalyzed reaction of alkynyl malonates with arylboronic acids is described. These arylative cyclizations proceed via an alkenyl-to-aryl 1,4-Rh(i) migration as a key step. Preliminary results of an enantioselective variant of these reactions are also presented.
RESUMEN
Nickel-catalyzed, highly diastereoselective annulations between activated allenes and 2-acetylarylboronic acid or 2-formylarylboronic acids are reported. No ligand for nickel is required, and the reactions proceed efficiently at room temperature to give a broad range of substituted 3-methyleneindan-1-ols. Preliminary results of an enantioselective variant are also described.
RESUMEN
The synthesis of multisubstituted pyrroles by the nickel-catalyzed reaction of N-tosyl alkynamides with arylboronic acids is reported. These reactions are triggered by alkyne arylnickelation, followed by cyclization of the resulting alkenylnickel species onto the amide. The reversible E/Z isomerization of the alkenylnickel species is critical for cyclization. This method was applied to the synthesis of pyrroles that are precursors to BODIPY derivatives and a biologically active compound.
RESUMEN
The enantioselective synthesis of highly functionalized chiral cyclopent-2-enones by the reaction of alkynyl malonate esters with arylboronic acids is described. These desymmetrizing arylative cyclizations are catalyzed by a chiral phosphinooxazoline/nickel complex, and cyclization is enabled by the reversible E/Zâ isomerization of alkenylnickel species. The general methodology is also applicable to the synthesis of 1,6-dihydropyridin-3(2H)-ones.
RESUMEN
Enantioselective nickel-catalyzed arylative cyclizations of substrates containing a Z-allylic phosphate tethered to an alkyne are described. These reactions give multisubstituted chiral aza- and carbocycles, and are initiated by the addition of an arylboronic acid to the alkyne, followed by cyclization of the resulting alkenylnickel species onto the allylic phosphate. The reversible E/Z isomerization of the alkenylnickel species is essential for the success of the reactions.
RESUMEN
We describe the design, synthesis, and opioid activity of fluoroalkene (Tyr1 -ψ[(Z)CF=CH]-Gly2 ) and trifluoroethylamine (Tyr1 -ψ[(S)/(R)-CF3 CH-NH]-Gly2 ) analogues of the endogenous opioid neuropeptide, Leu-enkephalin. The fluoroalkene peptidomimetic exhibited low nanomolar functional activity (5.0±2â nm and 60±15â nm for δ- and µ-opioid receptors, respectively) with a µ/δ-selectivity ratio that mimics that of the natural peptide. However, the trifluoroethylamine peptidomimetics, irrespective of stereochemistry, did not activate the opioid receptors, which suggest that bulky CF3 substituents are not tolerated at this position.
Asunto(s)
Analgésicos Opioides/farmacología , Encefalina Leucina/análogos & derivados , Hidrocarburos Fluorados/farmacología , Peptidomiméticos/farmacología , Analgésicos Opioides/síntesis química , Animales , Células CHO , Cricetulus , Encefalina Leucina/síntesis química , Encefalina Leucina/farmacología , Humanos , Hidrocarburos Fluorados/síntesis química , Peptidomiméticos/síntesis química , Receptores Opioides/agonistas , Estereoisomerismo , Relación Estructura-ActividadRESUMEN
Gold-catalyzed formal hetero-[4π+2π] cycloadditions of tert-butyl propiolates with carbonyl compounds proceeded efficiently to yield 4H-1,3-dioxine derivatives over a wide scope of substrates. With acetone as a promoter, gold-catalyzed cycloadditions of these propiolate derivatives with enol ethers led to the formation of atypical [4+2]-cycloadducts with skeletal rearrangement.
RESUMEN
Gold-catalyzed hetero-[4π + 2π]-cycloadditions of tert-butyl propiolates with unactivated nitriles are described; the resulting 6H-1,3-oxazin-6-ones are not easily accessible via conventional methods. This new finding enables a one-pot gold-catalyzed synthesis of highly substituted pyridines through sequential gold-catalyzed reactions of tert-butyl propiolates with nitriles, and then with electron-deficient alkynes in the same solvent. The utility of these [4 + 2]-cycloadditions is further expanded with various aldehydes, ketones and 2-phenyloxetane, yielding satisfactory yields of cycloadducts.
RESUMEN
Reported herein is the novel gold-catalyzed intermolecular [2+2+2] cycloaddition of ynamides with two discrete nitriles to form monomeric 4-aminopyrimidines, which are pharmaceutically important structural motifs. The utility of this new cycloaddition is demonstrated by the excellent regioselectivity obtained using a variety of ynamides and nitriles.
RESUMEN
We report the first success in the gold-catalyzed oxoarylations of nitriles with pyridine-derived N-oxides using gold carbenes as initiators. These oxoarylations were also achieved satisfactorily in intermolecular three-component oxidations, including diverse alkenyldiazo esters, nitriles, and pyridine-based oxides.
RESUMEN
Gold-catalyzed syntheses of 2,3-disubstituted indole derivatives from N-hydroxyanilines and allenes are described; these reactions require benzaldehyde as an additive to generate nitrones in situ. Our control experiments indicate that nitrones and water were indispensable in the reactions whereas N-hydroxyanilines alone were inactive nucleophiles. This synthetic method is compatible with allenes and N-hydroxyanilines with a reasonable range, further highlighting its synthetic utility.
Asunto(s)
Alcadienos/química , Aminofenoles/química , Benzaldehídos/química , Oro/química , Indoles/química , Catálisis , Indoles/síntesis químicaRESUMEN
We report two viable routes for the 1,2-difunctionalization of aminoalkynes using only oxidants. In the presence of a gold catalyst, nitrones enable the oxoamination of aminoalkynes 1 to form 2-aminoamides 2. With a suitable gold catalyst, nitrosobenzenes implement an alkyne/nitroso metathesis of the same substrates to give 2-oxoiminylamides 3. These two novel oxidations also provide 1,2-aminoalcohols with opposite regioselectivity via NaBH(4) reduction in situ.