RESUMO
The reaction of 1,1-bis(triflyl)ethylene generated in situ with enolizable carbonyls yielded δ-oxo-1,1-bis(triflyl)alkane derivatives. Their acidities in both the gas and solution phases were determined.
Assuntos
Alcanos/síntese química , Técnicas de Química CombinatóriaRESUMO
1,1,3,3-Tetrakis(trifluoromethanesulfonyl)propane (Tf(2)CHCH(2)CHTf(2)) is one of the most effective Brønsted acid precatalysts for the Mukaiyama aldol type reactions of sterically hindered ketones. By using Tf(2)CHCH(2)CHTf(2) in a range from 0.5 to 2.0 mol %, the vinylogous Mukaiyama aldol reaction of alpha-substituted cyclohexanones with 2-silyloxyfurans smoothly proceeded to give the aldol products in excellent yield without the loss of diastereoselectivity. Under similar conditions, acyclic ketene silyl acetals also performed as nice nucleophiles toward sterically hindered ketones. These findings suggest that Tf(2)CHCH(2)CHTf(2) induced Mukaiyama aldol type reactions can overcome the steric hindrance between reaction sites.
Assuntos
Ácidos/química , Aldeídos/química , Carbono/química , Cetonas/química , Espectroscopia de Ressonância Magnética , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
Silyl methide species in situ generated from 1,1,3,3-tetrakis(trifluoromethanesulfonyl)propane (Tf(2)CHCH(2)CHTf(2)) performed as an excellent acid catalyst for the vinylogous Mukaiyama-Michael reaction of alpha,beta-unsaturated ketones with 2-silyloxyfurans. Notably, the required loading of Tf(2)CHCH(2)CHTf(2) to obtain the 1,4-adducts in reasonable yield was significantly low (from 0.05 to 1.0 mol %). This carbon acid-mediated VMM reaction provides a powerful synthetic methodology to construct highly substituted gamma-butenolide structure.
Assuntos
Furanos/química , Hidrocarbonetos Fluorados/química , Compostos de Organossilício/química , Propano/análogos & derivados , Catálise , Cetonas/química , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Estrutura Molecular , Propano/química , EstereoisomerismoRESUMO
The reaction of trifluoroacetaldehyde N,O-acetal derivatives with 2 molar equivalents of alkyllithium reagents proceeded viabeta-elimination of fluoride followed by alkyl transfer from excess alkyllithium to the generated ketene N,O-acetal intermediate at the beta-carbon of fluorine groups.
Assuntos
Acetaldeído/análogos & derivados , Acetais/síntese química , Fluoretos/química , Acetaldeído/síntese química , Acetaldeído/química , Acetais/química , Alquilação , Etilenos/química , Cetonas/química , Nitrogênio/química , Oxigênio/químicaRESUMO
In(OTf)(3) was found to be a useful Lewis acid catalyst for direct alkylative Passerini reaction of aldehydes, isocyanides, and free aliphatic alcohols. In the present reaction, aromatic and alpha,beta-unsaturated aldehydes performed as nice substrates to give the corresponding alpha-alkoxy amide products in good yield.
Assuntos
Álcoois/química , Aldeídos/química , Cianetos/química , Mesilatos/química , Alquilação , CatáliseRESUMO
The intramolecular Diels-Alder reaction of an ester-tethered 1,3,9-decatriene system was significantly accelerated in ionic liquids such as [emim]BF(4), [bmim]BF(4) and [bdmim]BF(4). Under the present conditions, the IMDA reaction proceeded smoothly without the use of Lewis acid catalysts to give cis-fused bicyclic lactones in good yield with high diastereoselectivity.
Assuntos
Líquidos Iônicos/química , Alcenos/química , Ésteres/química , Cinética , Lactonas/química , Metais/química , Compostos Organometálicos/química , Estereoisomerismo , Especificidade por SubstratoRESUMO
1,1,3,3-Tetrakis(trifluoromethanesulfonyl)propane was found as an excellent Brønsted acid catalyst for the Mukaiyama-Michael reaction of alpha,beta-enones with 2-silyloxyfurans; using beta,beta-disubstituted enones as a Michael acceptor, an excellent yield construction of quaternary carbon centers could be achieved; in addition, very low catalyst loading of Brønsted acid was used in a range from 0.05 to 1.0 mol%.
Assuntos
Alcenos/química , Furanos/química , Cetonas/química , Mesilatos/química , Propano/análogos & derivados , Compostos de Vinila/síntese química , Catálise , Furanos/síntese química , Cetonas/síntese química , Propano/química , Compostos de Vinila/químicaRESUMO
In this paper, we describe the synthesis of (+)-(1R( *),2R( *))-2-[(1S( *))-1-amino-1-carboxy-2-(9H-xanthen-9-yl)-ethyl]-1-fluorocyclopropanecarboxylic acid (+)-16a, a compound, that is, fluorinated at the alpha position of the carboxylic acid in the cyclopropane ring of a group II mGluRs antagonist, 1 (LY341495), using a previously reported stereoselective cyclopropanation reaction. The fluorinated compound (+)-16a exhibited almost the same affinity (IC(50)=3.49 nM) for mGluR2 as 1 but had a superior pharmacokinetic profile. Furthermore, a marked elevation of the plasma levels of (+)-16a was observed following the administration of a prodrug, (+)-17.
Assuntos
Receptores de Glutamato Metabotrópico/antagonistas & inibidores , Xantenos/síntese química , Xantenos/farmacologia , Animais , Cristalografia por Raios X , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Modelos Moleculares , Estrutura Molecular , Pró-Fármacos/síntese química , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Ligação Proteica , Ratos , Receptores de Glutamato Metabotrópico/metabolismo , Relação Estrutura-Atividade , Xantenos/químicaAssuntos
Ácidos/química , Mesilatos/química , Alquilação , Catálise , Cristalografia por Raios X , Esterificação , Estrutura MolecularRESUMO
[reaction: see text] The intramolecular Diels-Alder reaction of 1,7,9-decatrienoate derivative with an ester tether is efficiently catalyzed by the bidentate Lewis acid, bis-aluminated trifluoromethanesulfonamide.
RESUMO
The acylzirconocene chloride complex as an acyl group donor reacts with omega-unsaturated alpha,beta-enones and -ynones under Pd-Me(2)Zn(Me(2)AlCl)-catalyzed conditions to give stereoselectively bicyclo[3.3.0] compounds through (i) formation of a Pd(II) intermediate by an oxidative addition of the Pd(0) catalyst to an enone function, (ii) cyclization of the Pd intermediate to an omega-unsaturated group, (iii) an acyl group transfer from zirconium to Pd metal, (iv) reductive elimination of the Pd metal, and (v) intramolecular cis-selective aldol reaction. [reaction: see text]
RESUMO
[reaction: see text]. The zirconium-mediated intramolecular ester transfer reaction of N-alkenyl carbamate derivatives proceeded to give alpha-substituted gamma-aminobutyric acid (GABA) derivatives in good to excellent yields. Quenching experiments of the reaction mixture with iodine or O2 indicated the presence of a cyclopropane intermediate. The resulting iodide was converted to 2-substituted pyrrolidine-3-carboxylate and/or alpha-alkylidene-gamma-aminobutyric acid derivatives in a stereospecific manner.
Assuntos
Zircônio/química , Ácido gama-Aminobutírico/análogos & derivados , Ácido gama-Aminobutírico/síntese química , Ésteres/química , Lactamas/químicaRESUMO
[reaction: see text] Radical cascade reaction with various 1,4-dienes and 1,4-enynes using dimethyl 2-(iodomethyl)cyclopropane-1,1-dicarboxylate as a homoallyl radical precursor smoothly proceeds through an iodine atom transfer mechanism to give functionalized bicyclo[3.3.0]octane derivatives in good yields.
RESUMO
[reaction: see text] N-monoallylation of meso-vicinal diamine bistrisylamides using a chiral pi-allyl-Pd catalyst proceeded in an enantioselective manner (up to 90% ee) to give desymmetrization products in good yields. The product was converted to the known sigma-receptor agonist in short steps. In addition, the present catalytic asymmetric N-allylation was applied to kinetic resolution of racemic-diamide.
Assuntos
Diaminas/síntese química , Paládio/química , Receptores sigma/agonistas , Catálise , Diaminas/farmacologia , Indicadores e Reagentes , Estrutura Molecular , EstereoisomerismoRESUMO
1,2- Or 1,3-asymmetric induction in the iodocarbocyclization reaction of 4-pentenylmalonate derivatives having a stereogenic center at an allylic or a homoallylic position has been investigated. The iodocarbocyclization reactions of 3-oxy-4-pentenylmalonate derivatives proceeded with high cis-selectivity through stereoelectronic control of the oxygenated substituent at an allylic position. In the reaction of (S)-2-siloxy-4-pentenylmalonate, an excellent diastereoselectivity was achieved through the utilization of double stereodifferentiation with a chiral titanium catalyst. Furthermore, as an application of the present reaction, the asymmetric syntheses of cyclosarkomycin and a synthetic intermediate of brefeldin A from optically pure 2- and 3-oxy-4-pentenylmalonate derivatives are also described.
RESUMO
A new and general method of iodine-mediated cyclization reactions of allyl or homoallyl carbamates, ureas, and amides was found to give N-cyclized products as single regioisomers. The present reaction proceeded in good yield through regiocontrol (N-cyclization > O-cyclization) and the increase in the reactivity of an ambident nucleophile by a basic metallic reagent. The N-cyclization selectivity was remarkably affected by the additive employed. The iodoaminocyclization reaction of the homoallyl carbamates and ureas with a chiral center at the homoallylic position was found to proceed with high 1,3-cis- and 1,3-trans-selectivity, respectively.
RESUMO
The iodocarbocyclization reaction of 4-alkenylmalonate derivatives proceeded with excellent enantioselectivity (>/=95% ee) in the presence of 10-40 mol % of Ti(TADDOLate)(2). The Ti(TADDOLate)(2)-mediated catalytic asymmetric reaction was extended to the enantiotopic group selective reaction of bisalkenylated malonates, giving rise to trisubstituted cyclopentanoid compounds with both high diastereoselectivity (86-94% de) and excellent enantioselectivity (>/=95% ee). An efficient synthesis of (+)-boschnialactone from the product of the present reaction was also achieved.
RESUMO
New axially chiral N-acryl-N-allyl-o-tert-butylanilide and N-(o-tert-butylphenyl)-2-methylmaleimide with high optical purity and definite absolute configurations were prepared from o-tert-butylaniline and (S)-O-acetyl lactic acid or (R)-2-methylsuccinic acid, respectively. Iodine- or Lewis acid-mediated asymmetric Diels-Alder reaction of these axially chiral compounds with various dienes proceeded with high endo and diastereofacial selectivity.
RESUMO
Under mild conditions the acyl group of acylzirconocene chloride 1 formed from an alkene or alkyne and [(C5 H5 )2 ZrHCl] reacts as an "unmasked" acyl anion. The Lewis acid mediated reactions with aldehydes that yield α-ketol products in high yields demonstrate the versatility of this reagent for C-C coupling.