RESUMO
A new method has been developed for the construction of dihydrobenzofurans from O-aryloxime ethers bearing an α-cyano group using a sequential regioselective isomerization/[3,3]-sigmatropic rearrangement/cyclization reaction in MeOH without any catalysts under neutral conditions at ambient temperature. The current transformation provides environmentally benign and atom-economical access to a variety of dihydrobenzofurans containing a quaternary carbon from readily available cyclic and acyclic oxime ethers.
Assuntos
Benzofuranos/síntese química , Éteres/química , Benzofuranos/química , Catálise , Ciclização , Estrutura Molecular , Nitrilas/síntese química , Nitrilas/química , Oximas/químicaRESUMO
The synthetic utility of N-alkoxyimidoyl halides is demonstrated using the palladium-catalyzed cross-coupling reaction. The Sonogashira and Suzuki-Miyaura coupling reactions of N-alkoxyimidoyl bromides produced versatile ketoxime ethers in good to excellent yields. A one-pot reaction of the imidoyl bromides with arylboronic acid and allylmagnesium bromide to produce N-arylamines via Suzuki-Miyaura coupling followed by domino reaction involving sequential addition-eliminative rearrangement-addition reactions was developed.
Assuntos
Aminas/química , Brometos/química , Imidas/química , Paládio/química , Aminas/síntese química , CatáliseRESUMO
Direct generation of a benzyl radical by C-H bond activation of toluenes and the addition reaction of the resulting radical to an electron deficient olefin were developed. The reaction of dimethyl fumarate with toluene in the presence of Et(3)B as a radical initiator at reflux afforded 2-benzylsuccinic acid dimethyl ester in good yield.
Assuntos
Compostos de Benzil/química , Carbono/química , Hidrogênio/química , Alcenos/química , Radicais Livres/química , Estrutura MolecularRESUMO
Alkynyl oxime ether underwent a gold-catalyzed domino reaction involving cyclization and subsequent Claisen-type rearrangement to afford trisubstituted isoxazoles in a direct, efficient, and regioselective manner. The products were successfully applied to the synthesis of unusual heterocycles as an illustration of the potential utility of the reaction.
Assuntos
Alcinos/química , Éteres/química , Ouro/química , Isoxazóis/síntese química , Oximas/química , Catálise , Técnicas de Química Combinatória , Ciclização , Isoxazóis/química , Estrutura MolecularRESUMO
A new efficient synthesis of 2-substituted tetrahydroquinolines has been achieved by the domino reaction of N-indanyl(methoxy)amines, which consists of three types of reactions: elimination of an alcohol, the rearrangement of an aryl group, and the addition of an organolithium or magnesium reagent. The synthetic utility of this approach is demonstrated by the stereoselective formal synthesis of (+/-)- martinellic acid.
Assuntos
Lítio/química , Magnésio/química , Compostos Organometálicos/química , Pirróis/síntese química , Quinolinas/síntese química , Alquilação , Catálise , Estrutura Molecular , Pirróis/química , Quinolinas/química , EstereoisomerismoRESUMO
Intermolecular hydroxyalkylation of alpha,beta-unsaturated imines involving Et3B-mediated regioselective alkyl radical addition and subsequent hydroxylation with molecular oxygen has been developed, in which N-borylenamine generated by trapping of the enaminyl radical with Et3B was a key intermediate in the proposed aerobic hydroxylation mechanism.
Assuntos
Aminas/química , Boranos/química , Compostos de Boro/química , Iminas/química , Oxigênio/química , Alquilação , Hidroxilação , Estereoisomerismo , Tolueno/químicaRESUMO
Two domino reactions of vinylcyclopropyl oxime ethers involving (i) thiyl radical addition, ring-opening, and hydroxylation reactions and (ii) thiyl radical addition, ring-opening, and aldol-type reactions were developed.
Assuntos
Amino Álcoois/síntese química , Oximas/síntese química , Compostos de Sulfidrila/química , Compostos de Vinila/síntese química , Aldeídos/química , Amino Álcoois/química , Radicais Livres/química , Estrutura Molecular , Oximas/química , Estereoisomerismo , Compostos de Vinila/químicaRESUMO
Nitrogen-containing compounds are core parts not only of natural and synthetic medicines but also of biologically active compounds including natural products. This review focuses on the development of new synthetic reactions for nitrogen-containing compounds via three methodologies: the reductive photocycloaddition reaction of enamides, radical addition reaction, and nucleophilic addition reaction. Newly developed reactions were successfully applied to the synthesis of various types of nitrogen-containing compounds including medicines, lead compounds to new drugs, natural alkaloids, and others.
Assuntos
Compostos de Nitrogênio/síntese química , Iminas/química , Preparações Farmacêuticas/síntese química , Fotoquímica , Espécies Reativas de Nitrogênio/química , Compostos de Sulfidrila/síntese química , Compostos de Sulfidrila/químicaRESUMO
The asymmetric total synthesis of martinellic acid, the first pyrrolo[3,2-c]quinoline alkaloid found in nature, is described. Three key steps in our synthesis of (-)-martinellic acid are the Bu(3)SnH-promoted radical addition-cyclization-elimination (RACE) reaction of an oxime ether with an alpha,beta-unsaturated ester to generate the pyrrolo[3,2-c]quinoline core, a chemoselective lactam carbonyl reduction, and guanidinylation under Mitsunobu reaction conditions. The key radical cyclization has also been investigated by using SmI(2). (-)-Martinellic acid was synthesized from commercially available methyl 4-bromo-3-methylbenzoate in fewer steps than previous syntheses and in an improved overall yield.
Assuntos
Pirróis/síntese química , Quinolinas/síntese química , Ciclização , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Pirróis/química , Quinolinas/química , Espectrofotometria InfravermelhoRESUMO
Direct observation of the unstable intermediate in the radical addition reaction of the oxime ether 1 mediated by triethylborane (Et(3)B) is described using (1)H and (11)B micro channeled cell for synthesis monitoring (MICCS), which was recently developed as an interfacing microchip for NMR. It was possible that the signal of the intermediate was observed as a result of using MICCS technique with a standard NMR instrument. This result supports the structure of the intermediate analyzed by diffusion-ordered spectroscopy (DOSY) NMR method in a previous paper. The procedure of micro channeled cell for synthesis monitoring-nuclear magnetic resonance (MICCS-NMR) was much easier than that of DOSY method. It was proven that it could be applied to the reaction in an anhydrous condition.
Assuntos
Boranos/química , Espectroscopia de Ressonância Magnética/métodos , Oximas/química , Boro/análise , Espectroscopia de Ressonância Magnética/instrumentação , PrótonsRESUMO
The structures of the components in the triethylborane-mediated radical addition reaction of oxime ether were investigated by 1H- and 3D-DOSY NMR methods. It has been impossible to physically separate the unstable intermediates; therefore, the structures were thus far unidentified. It has been possible to elucidate the structures of these unstable intermediates using Diffusion-Ordered Spectroscopy (DOSY) methods for the reaction in an NMR tube. The DOSY methods resolved the spectra of each starting compound, intermediate and product having different diffusion coefficients. The structure of the intermediate was shown to be due to the bonding of diethylborane to the nitrogen atom of the alkoxyamino group.
Assuntos
Boranos/química , Compostos de Boro/química , Hidroxilaminas/química , Espectroscopia de Ressonância Magnética/métodos , Oximas/química , Difusão , Éteres/química , Estrutura Molecular , Nitrogênio/análiseRESUMO
Relationship between a radical species and radical acceptors of three different types of double bond in radical addition-cyclization was systematically investigated. Substrates carrying alpha,beta-unsaturated amide, isolated olefin, and oxime ether moieties underwent radical addition-cyclization to give differently substituted lactams depending upon the radicals used. The sulfanyl radical addition-cyclization of the substrate proceeded smoothly to give the 5-membered lactam having an alkoxyamino group as a result of preferable addition of an intermediary alpha-carbonyl radical to the oxime ether. On the other hand, the triethylborane-mediated radical addition-cyclization gave the lactam bearing an iodomethyl group as a result of addition to an intermediary alpha-carbonyl radical to isolated olefin. The different regioselectivity was explained by the stability of the intermediary radical and the interaction between SOMO and HOMO.
Assuntos
Radicais Livres/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
The intermolecular radical addition to chiral nitrones 2, 4, 5, and 16 was studied. The isopropyl radical addition to Oppolzer's camphorsultam derivative 2 of glyoxylic nitrone proceeded with excellent diastereoselectivity to give the desired isopropylated product 3a accompanied by the diisopropylated product 3b. A high degree of stereocontrol in the reaction of cyclic nitrone 4 was achieved. The ethyl radical addition to nitrone 4 with triethylborane afforded the desired ethylated product 9a accompanied by the diethylated product 10a and the ethylated nitrone 11a. To evaluate the utility of cyclic nitrone 4, several alkyl radicals were employed in the addition reaction, which afforded the alkylated products 9b-d with excellent diastereoselectivities. In the presence of Mg(ClO(4))(2), the ethyl radical addition to BIGN 16 afforded selectively syn isomers. In contrast, the alkyl radical addition to 16 took place even in the absence of Lewis acid to give anti isomers.
Assuntos
Óxidos de Nitrogênio/química , Radicais Livres , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , EstereoisomerismoRESUMO
The imino 1,2-Wittig rearrangement of hydroximates containing a furan ring provides a novel method for the synthesis of beta-hydroxy-alpha-amino acids. Upon treatment with LDA, hydroximates smoothly underwent the rearrangement to give Z-2-hydroxyoxime ethers in good yield, which were converted into both cis- and trans-oxazolidinones with high stereoselectivity. The cis- and trans-oxazolidinones were stereoselectively converted into erythro- and threo-beta-hydroxyphenylalanines, respectively, via the oxidative cleavage of a furan ring, ring-opening of oxazolidinone, and deprotection.
Assuntos
Oximas/síntese química , Fenilalanina/análogos & derivados , Fenilalanina/síntese química , Acilação , Indicadores e Reagentes , Oxirredução , EstereoisomerismoRESUMO
The addition of carbon radicals to glyoxylic imines was studied using zinc dust as a radical initiator. The zinc-mediated radical reaction of glyoxylic oxime ethers and hydrazones proceeded smoothly to give the alkylated products via a carbon-carbon bond-forming process in aqueous media. The reaction of the oxime ethers and hydrazones having an Oppolzer's camphorsultam group provided the corresponding alkylated products, which could be converted into enantiomerically pure alpha-amino acids. The diastereoselectivities observed in the reaction of hydrazones were better than those obtained in the reaction of oxime ethers.
Assuntos
Aminoácidos/química , Carbono/química , Éteres/química , Radicais Livres/química , Glioxilatos/química , Hidrazonas/química , Iminas/química , Zinco/farmacologiaRESUMO
Tandem radical addition-cyclization of oxime ethers anchored to polymer support was studied. The reaction of oxime ethers with stannyl radical proceeded effectively by the use of triethylborane as a radical initiator. The alkyl radical addition-cyclization reactions of oxime ether connected with alpha,beta-unsaturated carbonyl group proceeded under iodine atom-transfer reaction conditions to give the functionalized azacycles via two carbon-carbon bonds-forming process.
Assuntos
Boranos/metabolismo , Éteres/metabolismo , Radicais Livres/metabolismo , Oximas/metabolismo , Polímeros/metabolismo , Boranos/química , Éteres/química , Radicais Livres/química , Oximas/química , Polímeros/químicaRESUMO
[reaction: see text] Stabilized primary radicals can be formed from alkyl halides in an atom transfer process with Et(3)B. This process depends on the strength of the carbon-halogen bond and the stability of the resulting primary radical. Radicals formed from benzyl iodide and ethyl iodoacetate add to glyoxylic oxime ethers; however, more electrophilic radicals do not. Glyoxylic oxime ethers are also good radical acceptors for heterocyclic carbon-centered secondary radicals, giving novel alpha-amino acid derivatives.