RESUMEN
Diazophosphonates, readily prepared from α-ketophosphonates by oxidation of the corresponding hydrazones in batch or in flow, are useful partners in 1,3-dipolar cycloaddition reactions to alkynes to give N-H pyrazoles, including the first intramolecular examples of such a process. The phosphoryl group imbues a number of desirable properties into the diazo 1,3-dipole. The electron-withdrawing nature of the phosphoryl stabilizes the diazo compound making it easier to handle, whilst the ability of the phosphoryl group to migrate readily in a [1,5]-sigmatropic rearrangement enables its transfer from C to N to aromatize the initial cycloadduct, and hence its facile removal from the final pyrazole product. Overall, the diazophosphonate acts as a surrogate for the much less stable diazoalkane in cycloadditions, with the phosphoryl group playing a vital, but traceless, role. The cycloaddition proceeds more readily with alkynes bearing electron-withdrawing groups, and is regiospecific with asymmetrical alkynes. The potential of diazophosphonates for use in bioorthogonal cycloadditions is demonstrated by their facile addition to strained alkynes.
Asunto(s)
Alquinos , Pirazoles , Reacción de Cicloadición , HidrazonasRESUMEN
A new route to spiro-oxetanes, potential scaffolds for drug discovery, is described. The route is based on the selective 1,4-C-H insertion reactions of metallocarbenes, generated from simple carbonyl precursors in flow or batch mode, to give spiro-ß-lactones that are rapidly converted into spiro-oxetanes. The three-dimensional and lead-like properties of spiro-oxetanes are illustrated by the conversion of the 1-oxa-7-azaspiro[3,5]nonane scaffold into a range of functionalized derivatives.
Asunto(s)
Diseño de Fármacos , Éteres Cíclicos/química , Compuestos de Espiro/química , Carbono/química , Cristalografía por Rayos X , Hidrazonas/química , Hidrógeno/química , Lactonas/síntesis química , Lactonas/química , Conformación Molecular , Oxidación-ReducciónRESUMEN
A highly stereoselective route to functionalized pyrrolidines by the metal-catalyzed diverted N-H insertion of a range of diazocarbonyl compounds with ß-aminoketone derivatives is described. A number of catalysts (rhodium(II) carboxylate dimers, copper(I) triflate, and an iron(III) porphyrin) are shown to promote the process under mild conditions to give a wide range of highly substituted proline derivatives. The reaction starts as a metallocarbene N-H insertion but is diverted by an intermolecular aldol reaction.
RESUMEN
Highly reactive metal carbenes, generated from simple ketones via diazo compounds, including diazo-amides and -phosphonates, using a recyclable reagent in-flow, are transient but versatile electrophiles for heteroatom alkylation reactions and for epoxide formation. The method produces no organic waste, with the only by-products being water, KI and nitrogen, without the attendant hazards of isolation of intermediate diazo compounds.
Asunto(s)
Compuestos Azo/química , Oxidantes/química , Polímeros/química , Alquilación , Amidas/química , Catálisis , Compuestos Epoxi/química , Halógenos/química , Cetonas/química , Ácidos Fosforosos/químicaRESUMEN
Copper- or rhodium-catalyzed reactions of diazocarbonyl compounds with ß-hydroxyketones give highly substituted tetrahydrofurans with excellent diastereoselectivity. Under mild conditions, the single-step process starts as a carbene O-H insertion reaction, but is diverted by an intramolecular aldol reaction.
Asunto(s)
Furanos/síntesis química , Metano/análogos & derivados , Catálisis , Cobre/química , Furanos/química , Metano/síntesis química , Metano/química , Rodio/química , EstereoisomerismoRESUMEN
A new reagent for the oxidation of hydrazones to diazo compounds is described. N-Iodo p-toluenesulfonamide (TsNIK, iodamine-T) allows the preparation of α-diazoesters, α-diazoamides, α-diazoketones and α-diazophosphonates in good yield and in high purity after a simple extractive work-up. α-Diazoesters were also obtained in high yield from the corresponding ketones through a one-pot process of hydrazone formation/oxidation.