RESUMO
Dimethylzinc-mediated radical conjugate addition reaction of dimethyl alkylidenemalonates with iodomethyl pivalate gave a high yield of the α,ß-dual oxymethylation product in one pot under air and the ß-pivaloyloxymethylation product under argon.
Assuntos
Malonatos/síntese química , Radicais Livres/síntese química , Radicais Livres/química , Malonatos/química , Metilação , Estrutura MolecularRESUMO
Triethylborane-mediated tin-free radical alkylation of N-alkoxycarbonyl-imines, such as N-Boc-, N-Cbz-, and N-Teoc-imines, proceeded smoothly at a low temperature (-78 to -20 °C) to give the corresponding adducts in high yield. Although the formation of isocyanate was the major unfavorable reaction at room temperature, a one-pot conversion of N-Boc-imine to N-ethoxycarbonyl-adduct was possible through the corresponding isocyanate generated in situ. The higher performance of N-alkoxycarbonyl-imine than those of N-Ts- and N-PMP-imines is rationalized by a moderate electron-withdrawing character of an alkoxycarbonyl group that makes both addition of alkyl radical and trapping of the resulting aminyl radical by triethylborane efficiently fast.
Assuntos
Boranos/química , Iminas/química , Alquilação , Catálise , Radicais Livres/química , Isocianatos/química , Metilação , Estanho/químicaRESUMO
Enantio- and diastereoselective one-pot synthesis of three- to seven-membered cis-azaheterocycles was achieved using a triggered asymmetric conjugate addition reaction of lithium amide with an enoate, followed by alkylation of the resulting lithium enolate with α,ω-dihaloalkane and N-alkylation. Isomerization of cis-azaheterocycles with a base yielded the trans-product, constituting a one-pot synthesis of cis-azacycles and a two-step synthesis of trans-azacycles. The four-step asymmetric synthesis of nemonapride highlights the general utility of the method.
Assuntos
Compostos Aza/síntese química , Cicloparafinas/síntese química , Compostos Aza/química , Ciclização , Cicloparafinas/química , Estrutura Molecular , EstereoisomerismoRESUMO
A method for the synthesis of cyclic amides via phosphazene base-catalyzed intramolecular hydroamidation of amide alkenes was developed. The reaction using a catalytic amount of P4-base had a good functional group tolerance and a broad substrate scope and could also be used to synthesize lactam, cyclic urea, and oxazolidinone compounds. This catalytic system was expanded to a one-pot intramolecular hydroamidation and intermolecular hydroalkylation. Deuterium labeling and radical trapping experiments provided mechanistic insights into the catalytic cycle of the hydroamidation reaction.
RESUMO
Chiral N-heterocyclic carbene ligands were electronically and sterically tuned to improve γ-selectivity in copper(I)-catalyzed asymmetric allylic arylation of aliphatic allylic bromides with several aryl Grignard reagents. High γ-selectivity was realized when either the aryl group of the Grignard reagent or the aryl group on the N-substituent of the carbene ligand was electron-deficient or when either the carbene ligand or allylic bromide was bulky. The results indicated that electron deficiency and steric hindrance of the initially formed σ-allyl copper intermediate enhance the rate of the reductive elimination to give γ-products as major isomers.
Assuntos
Cobre/química , Compostos Heterocíclicos/química , Hidrocarbonetos Bromados/síntese química , Metano/análogos & derivados , Compostos Organometálicos/química , Catálise , Elétrons , Hidrocarbonetos Bromados/química , Metano/química , Estrutura Molecular , EstereoisomerismoRESUMO
Stereoselective formal synthesis of (+)-allokainic acid was accomplished starting from L-glutamate by using a thiol-mediated acyl radical cyclization as a key step. The cyclization of a formylalkenoate proceeded in a highly diastereoselective manner to give trans-4,5-disubstituted pyrrolidin-3-one without the production of the cis-isomer. The pyrrolidinone was then converted into the established synthetic intermediate of (+)-allokainic acid via the iron-catalyzed coupling reaction with an isopropenyl Grignard reagent.
Assuntos
Ácido Caínico/análogos & derivados , Ciclização , Ácido Glutâmico/síntese química , Ácido Glutâmico/química , Ácido Caínico/síntese química , Ácido Caínico/química , Estereoisomerismo , Compostos de Sulfidrila/síntese química , Compostos de Sulfidrila/químicaRESUMO
Enantiomerically enriched sulfonamides were synthesized by the radical addition of an acetal to enantiomerically pure N-sulfinyl imines using dimethylzinc-air and boron trifluoride diethyl etherate. Higher levels of stereocontrol were observed by using a mesitylenesulfinyl group. Furthermore, an amine and an amino alcohol with high enantiomeric purity were obtainable from the sulfonamide product.
Assuntos
Acetais/química , Iminas/química , Sulfonamidas/síntese química , Acetais/síntese química , Boranos/química , Iminas/síntese química , Compostos Organometálicos/química , Estereoisomerismo , Sulfonamidas/químicaRESUMO
A catalytic asymmetric conjugate arylation of acyclic alpha,beta-unsaturated ketones with arylboronic acids was catalyzed by 3 mol% of chiral amidomonophosphane 1-rhodium(I) in the presence of potassium hydroxide in a mixture of 1,4-dioxane and water at 70 degrees C to afford 1,4-conjugate arylated acyclic ketones with high enantiomeric excess in high chemical yield. Thirteen examples of the reaction demonstrate the general applicability of the catalytic system.
Assuntos
Fosfinas/química , Ródio/química , Ácidos Borônicos/química , Catálise , Cetonas/química , Fosfinas/síntese química , EstereoisomerismoRESUMO
Cyclic and acyclic ether or acetal radicals were generated directly from ethers or acetals by the action of dimethylzinc-air, and their subsequent conjugate addition reaction with alkylidenemalonates afforded the corresponding conjugate adducts in reasonably high yields. The reaction with benzylidenemalonates bearing formyl and imino groups gave chemoselectively the conjugate addition products. The asymmetric reaction of bis(8-phenylmenthyl) benzylidenemalonate proceeded diastereoselectively to provide the adduct with 93:7 dr.
Assuntos
Acetais/química , Malonatos/química , Compostos Organometálicos/química , Cristalização , Éteres/química , Radicais Livres/química , Indicadores e Reagentes , Espectroscopia de Ressonância Magnética , EstereoisomerismoRESUMO
Asymmetric radical addition of ethers to enantiopure aromatic N-p-toluenesulfinyl aldimines has been achieved. The requisite radicals were generated by dimethylzinc-air. Lewis acid activation of the N-p-toluenesulfinyl aldimines followed by radical addition gives a mixture of sulfinamide and sulfonamide products. Subsequent treatment of the mixture with dry m-CPBA affords the sulfonamide product in enantiomerically enriched form. [reaction: see text]
Assuntos
Éteres/química , Iminas/química , Compostos Organometálicos/química , Ácidos Sulfínicos/química , Tolueno/análogos & derivados , Tolueno/química , Ar , Cromatografia Líquida de Alta Pressão , Radicais Livres/química , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Conformação Molecular , Estereoisomerismo , SulfonamidasRESUMO
[reaction: see text] A dimethylzinc-air initiator was applied to the generation of primary alkyl radicals from alkyl iodides. The addition of the generated primary alkyl radicals to N-tosylimines was accelerated by the action of boron trifluoride-diethyl etherate and copper(II) triflate to give the corresponding adducts in good yields after 2-3 h. Air oxygen was essential for the reaction to proceed, showing involvement of a radical process in the reaction.
RESUMO
[reaction: see text] The product distribution of the three-component reaction of aldehydes, arylamines, and THF was dependent on a radical initiator, preferentially giving the corresponding THF adducts of imines with dimethylzinc and adducts of aldehyde with triethylborane.
RESUMO
Ethers undergo addition to imines in the presence of dimethylzinc and air through a radical process. [reaction: see text]
RESUMO
A chiral ligand- and lithium amide-assisted asymmetric conjugate addition of lithium enolate of propionate to cyclopentenecarboxylate gave the corresponding lithium enolate, whose allylation gave the key intermediate of the marine alkaloid halichlorine as a single diastereomer with moderate enantioselectivity.
Assuntos
Alcaloides/síntese química , Lítio/química , Compostos Organometálicos/química , Compostos de Espiro/síntese química , Alcaloides/química , Alquilação , Catálise , Ésteres , Estrutura Molecular , Compostos de Espiro/química , EstereoisomerismoRESUMO
Chiral diether ligand-controlled asymmetric conjugate addition of a lithium amide to cyclopentenecarboxylate and subsequent in situ alkylation gave a chiral cyclopentane derivative bearing a quaternary carbon with high enantio- and diastereoselectivity. The cyclopentane derivative was converted successfully to (-)-aspidospermidine.
Assuntos
Amidas/química , Alcaloides Indólicos/síntese química , Lítio/química , Quinolinas/síntese química , Alquilação , Aminação , Catálise , Ciclopentanos/síntese química , Ciclopentanos/química , Alcaloides Indólicos/química , Estrutura Molecular , Quinolinas/química , EstereoisomerismoRESUMO
Two ways for the synthesis of binaphthyl were examined based on a chiral ligand-mediated asymmetric conjugate addition of 1-naphthyllithium to naththalene-2-carboxylic acid 2,6-di-t-butyl-4-methoxyphenyl esters. The one pot method by conjugate addition-elimination gave a relatively higher enantioselectivity than the two step synthesis based on addition and subsequent oxidative aromatization.
Assuntos
Naftalenos/química , Estrutura MolecularRESUMO
Highly enantioselective rhodium-catalyzed addition of arylboroxines to N-phosphinoylaldimines was realized by the steric tuning of a diphenylphosphorus moiety to a di(o-tolyl)phosphorus moiety of a chiral amidomonophosphane. The presence of MS 4 A in a 5:1 solvent mixture of dioxane-propanol was essential to afford the corresponding diarylmethylamines in high yield.
Assuntos
Compostos de Boro/química , Iminas/química , Metilaminas/síntese química , Compostos Organometálicos/química , Fosfinas/química , Ródio/química , Catálise , Metilaminas/química , Estrutura Molecular , EstereoisomerismoRESUMO
Two 1:1 noncovalent mixed aggregates between a lithium enolate and two diastereomeric lithium amides have been identified spectroscopically in THF. The NMR data, as well as DFT theoretical calculations, shine some light on a puzzling reversal of induction, observed when switching from one diastereomer of the amide to the other in the enantioselective Michael addition of the lithium enolate to an unsaturated ester.
Assuntos
Amidas/química , Lítio/química , Compostos Organometálicos/química , Catálise , Espectroscopia de Ressonância Magnética , Estrutura Molecular , EstereoisomerismoRESUMO
Consecutive cyclization of allylaminoalkenes by tandem aminolithiation-carbolithiation proceeded smoothly by using a lithium amide as a lithiating agent as well as protonating agent to give bicyclic amines, octahydroindolizine and hexahydro-1 H-pyrrolizine, in reasonably high yield and diastereoselectivity.