RESUMO
Chiral gamma-substituted allenamides have been shown to undergo efficient gold-catalyzed and N-iodosuccinimide-mediated cyclization to highly functionalized dihydrofurans. These reactions proceed rapidly and without loss of stereochemistry.
Assuntos
Alcadienos/química , Amidas/química , Furanos/química , Ouro/química , Succinimidas/química , Catálise , Ciclização , Estrutura Molecular , EstereoisomerismoRESUMO
Cobalt(III) acetate and cyanide complexes of a series of 5,12-dioxocyclams capped across the 1,8-position by 4-substituted pyridines or pyrazine were synthesized and fully characterized. Both the spectroscopic and structural parameters for these complexes were remarkably insensitive to the electronic nature of the capping group, which ranged from the pi-accepting pyrazine group to the sigma-donating 4-[(dimethylamino)phenyl]pyridyl group. All of the complexes underwent an irreversible, one-electron reduction [Co(III)-->Co(II)] at potentials ranging from -0.95 V vs saturated calomel electrode (SCE) for the pyrazine-capped cobalt acetate complex to -1.36 V vs SCE for the pyridine-capped cobalt cyanide complexes. Pyridine-capped cobalt(III) cyanide complex underwent reaction with Rh2(OAc)4 and ruthenium(II) phthalocyanine[bis(benzonitrile)] to form tetrametallic and trimetallic complexes through coordination bridging by the cyanide nitrogen lone pair. These complexes represent two quite different structural types for cyanide-bridged polymetallics. Complex has a relatively long (2.192 A) cyanide N-to-Rh bond, and the CN-Rh bond angle (157.6 degrees) is strongly distorted from linear. In contrast, complex has a substantially shortened cyanide N-to-Ru bond (2.017 A) and an almost linear arrangement along the entire bridging axis of the molecule.
Assuntos
Cobalto/química , Compostos Heterocíclicos/química , Compostos Organometálicos/química , Compostos Organometálicos/síntese química , Piridinas/química , Cristalografia por Raios X , Espectroscopia de Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética/normas , Modelos Moleculares , Estrutura Molecular , Padrões de Referência , Sensibilidade e Especificidade , Espectrofotometria Infravermelho/métodos , Espectrofotometria Ultravioleta/métodos , EstereoisomerismoRESUMO
Propargylic boranes generated by lithiation of optically active N-propargyloxazolidinones undergo reaction with a range of aldehydes to produce gamma,gamma-disubstituted allenamides with good diastereoselectivity.
Assuntos
Alcadienos/síntese química , Amidas/síntese química , Compostos de Boro/química , Alcadienos/química , Amidas/química , Estrutura Molecular , EstereoisomerismoRESUMO
Pyridine-capped 5,12-dioxocyclams were coupled "back-to-back" directly, with one or two intervening phenyl groups, an ethynyl group, or a diazo group via Suzuki, Sonogashira, or reductive coupling of the 4-nitropyridine monocyclam. These bis-dioxocyclams linked through extended pi-conjugated systems were complexed to copper(II) and cobalt(III), producing bis-metal complexes which were characterized spectroscopically and electrochemically. These studies gave little evidence for electronic communication between metal centers across the pi-conjugated linkers.
Assuntos
Cobre/química , Compostos Heterocíclicos/química , Compostos Heterocíclicos/síntese química , Compostos Organometálicos/química , Compostos Organometálicos/síntese química , Piridinas/química , Piridinas/síntese química , Cristalografia por Raios X , Eletroquímica , Ligantes , Conformação MolecularRESUMO
Reaction of optically active alpha-oxazolidinonylallenylstannanes with oxiranes in the presence of BF3.OEt2 produced beta-hydroxypropargylamines with high syn diastereoselectivity and high enantioselectivity through an initial Lewis-acid-catalyzed rearrangement of the oxirane to the corresponding aldehyde via an alkyl, aryl, or hydride shift. This permits the use of readily available oxiranes as alternatives to aldehydes that are difficult to prepare and/or unstable.
Assuntos
Aldeídos/química , Compostos de Epóxi/química , Compostos de Estanho/química , Ácidos/química , Aminação , Catálise , Óxido de Etileno/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Rotação Ocular , EstereoisomerismoRESUMO
Carbocyclic 4'-methyl and 4'-cyano nucleoside analogues were synthesized using the Michael reaction to introduce the 4'-substituent and Pd-catalyzed allylic substitution to introduce the nucleoside base. Use of both the desired beta- and undesired alpha-1'-carbonate diastereomers in the Pd-catalyzed substitution was demonstrated in principle by epimerization of the alpha-diastereomer and kinetic diastereodifferentiation of a 1:1 alpha/beta mixture of 1'-carbonates.
Assuntos
Ciclopentanos/química , Nucleosídeos/síntese química , Ciclização , Conformação Molecular , Nucleosídeos/química , EstereoisomerismoRESUMO
1-Deoxy-D-galactohomonojirimycin was synthesized in seven steps from optically pure allenylstannane 4 and L-lactate-derived aldehyde 5 in 48% overall yield. The key step was the Lewis acid catalyzed reaction of 4 and 5 to give the syn-amino alcohol in excellent yield and very high diastereoselectivity.
Assuntos
Galactose/análogos & derivados , Galactose/síntese química , Compostos Organometálicos/química , Piperidinas/síntese química , Estanho/química , 1-Desoxinojirimicina/análogos & derivados , Aldeídos/química , Alcaloides/química , Catálise , Ciclização , Galactose/química , Indicadores e Reagentes , Ácido Láctico/química , Estrutura Molecular , Piperidinas/análise , EstereoisomerismoRESUMO
Lithiation/stannylation of optically active N-propargyloxazolidinones produced optically active alpha-oxazolidinonylallenylstannanes. Reaction of these with aldehydes in the presence of BF(3).OEt(2) produced beta-hydroxypropargylamines with high syn diastereoselectivity and ee. These were converted to gamma-hydroxy-beta-amino acids by oxidative cleavage of the alkyne.
Assuntos
Compostos de Estanho/síntese química , Espectroscopia de Ressonância Magnética , Oxirredução , Espectrofotometria Ultravioleta , Estereoisomerismo , Compostos de Estanho/químicaRESUMO
A series of 4-substituted pyridine-capped 5,12-dioxocyclams was synthesized and fully characterized. The 4-substituent varied from electron-withdrawing groups (NO2, NO, CN) to electron-donating groups (NHCbz, NH2). The most versatile substituent was the 4-bromo group, which could be replaced by a variety of groups using Stille, Sonogashira, or Buchwald-Hartig palladium-catalyzed chemistry. Copper complexes of a majority of these capped dioxocyclams were synthesized and characterized as well.
Assuntos
Aminas/química , Compostos Heterocíclicos/química , Nitrogênio/química , Piridinas/química , Cobre/química , Cristalografia por Raios X , Compostos Heterocíclicos/síntese químicaRESUMO
A four-step synthesis of the title compound starting from methyl acrylate, ethylenediamine, and dimethyl malonate is reported. The synthesis can be run on a multigram scale and is operationally simple. The use of protecting groups is avoided by utilizing the trioxocyclam as the key coupling intermediate.
Assuntos
Fármacos Anti-HIV/síntese química , Compostos Heterocíclicos/síntese química , Acrilatos , Benzilaminas , Ciclamos , Etilenodiaminas/química , Indicadores e Reagentes , Espectroscopia de Ressonância MagnéticaRESUMO
(Methyl)(methoxy)-5,12-dioxocyclam 1 was alkylated on the secondary amines (capped) with 2,6-bis(bromomethyl)pyrazine. The resulting macrocycle was complexed to copper(II) to produce a five-coordinate complex 5a which was fully characterized by a range of spectroscopic methods (IR, UV-vis, ESR) as well as by X-ray crystallography. The structure of this complex is similar to the previously reported pyridine complex, with the five-coordinate copper having distorted square pyramidal geometry and a Cu-Pz bond length of 2.125 A. Attempts to prepare this same complex under microwave irradiation instead produced a trinuclear complex 6a having an octahedral copper(II) center complexed to two pyrazine-cyclam copper units through the amide carbonyl oxygen and the methoxyl group oxygen of the cyclam unit. The X-ray crystal structure of the trinuclear complex showed extensive distortion in the cyclam rings. The remote nitrogen of pyrazine-cyclam complex 5a was capable of coordinating an additional metal. Treatment with RuCl(2)(DMSO)(4) or Rh(2)(OAc)(4), respectively, produced trimetallic Cu-Ru-Cu complex 7 or tetrametallic Cu-Rh-Rh-Cu complex 8. The latter was fully characterized, including an X-ray crystal structure, and had two pyrazine-cyclam complexes bridged by a Rh(2)(OAc)(4) unit through the remote pyrazine nitrogens. There was little distortion in the pyrazine-cyclam copper units as compared to complex 5a: the four metals were collinear, and the two cyclam units were eclipsed. All of the copper complexes were subjected to cyclic voltametry measurements, and no reversible redox changes were observed. Magnetic measurements of 6a and 8 showed the copper atoms to be weakly antiferromagnetically coupled.
Assuntos
Hidrocarbonetos Aromáticos com Pontes/química , Pirazinas/química , Cobre , Cristalografia por Raios X , Eletroquímica , Espectroscopia de Ressonância de Spin Eletrônica , Indicadores e Reagentes , Espectroscopia de Ressonância Magnética , Magnetismo , Modelos Moleculares , Conformação Molecular , Ródio/química , Espectrofotometria UltravioletaRESUMO
Several dioxocyclams containing quinoxaline moieties, as well as their nickel(II) complexes were synthesized and studied for their ability to bind and oxidatively cleave DNA. Although no evidence for binding by intercalation was found, the ability of the Ni(II) complexes to cleave DNA in the presence of Oxone was strongly dependent on both the nature and the spatial orientation of the quinoxaline moieties, suggesting at least transient association of these complexes with DNA.
Assuntos
DNA/química , Compostos Heterocíclicos/síntese química , Substâncias Intercalantes/síntese química , Níquel/química , Compostos Organometálicos/síntese química , Quinoxalinas/síntese química , Catálise , Cristalografia por Raios X , DNA/efeitos dos fármacos , Compostos Heterocíclicos/farmacologia , Substâncias Intercalantes/farmacologia , Estrutura Molecular , Compostos Organometálicos/farmacologia , Oxirredução , Plasmídeos/química , Quinoxalinas/farmacologia , Estereoisomerismo , Ácidos Sulfúricos/químicaRESUMO
Butenolides 5a and 13 were used as optically active templates in the de novo synthesis of 4'-disubstituted nucleoside analogues. The butenolides were reduced and acylated in situ to give acetates 10 and 14. Vorbrüggen coupling gave the protected nucleoside analogues 11 and 15. Reduction of 11 gave 4'-ethoxy-2',3'-dideoxythymidine (6) and deprotection of 15 gave 4'-ethoxy-2',3'-dideoxydidehydrothymidine (7). The cis-dihydroxylation of a variety of butenolides occurred with the major product formed from oxidation of the beta-face.
Assuntos
Furanos/química , Nucleosídeos/química , Nucleosídeos/síntese química , 4-Butirolactona/análogos & derivados , Hidroxilação , Estrutura Molecular , EstereoisomerismoRESUMO
4'-Substituted nucleoside analogues have been synthesized using palladium-catalyzed asymmetric allylic amination conditions. A kinetic discrimination between the diastereomeric lactol acetates (3) produced the desired aminated products (6a-d) and recovered acetate (alpha-3) in high yields and <97:3 diastereoselectivity. Epimerization of the recovered lactol acetate (alpha-3) produced a 60:40 alpha/beta mixture of (3), which could be resubjected, in principle, to the palladium-catalyzed asymmetric allylic amination conditions.
Assuntos
Acetatos/química , Química Orgânica/métodos , Didesoxinucleosídeos/química , Didesoxinucleosídeos/síntese química , Paládio/química , Adenina/química , Alquilação , Catálise , Cromatografia em Camada Fina , Citosina/química , Cinética , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Estereoisomerismo , Timina/química , Uracila/químicaRESUMO
The metal-catalyzed allylic substitution reaction of 5a,b and 6a was examined. Reaction with stabilized nucleophiles led to exclusive attack at the less-hindered allylic terminus, and the stereoselectivity varied with the bidentate ligand used but favored retention. The yields and reaction times were improved with the use of microwaves. Alkylation via transmetalation was only observed with phenyl- and vinylstannatranes and gave regio- and stereoselectivity opposite those observed with the stabilized anions. The epimeric carbonates 5a and 5b displayed very different reactivities. Catalysts containing metals other than palladium were completely unreactive and led to recovered starting material.
Assuntos
Alcenos/química , Compostos Organometálicos/química , Alcenos/síntese química , Catálise , Ciclopentanos/química , Paládio/química , EstereoisomerismoRESUMO
The ring expansion of 22 differently beta-substituted alpha-methyl-alpha-methoxycyclobutanones by diazomethane was studied. Migration of the less-substituted alpha-carbon was favored with the single exception of a very sterically hindered beta-benzyloxy beta-substituent.
RESUMO
Photolysis of cyclic chromium alkoxycarbene complexes with an optically active ene-carbamate gave spirofused, optically active cyclobutanones. Baeyer-Villiger ring expansion followed by further functionalization gave optically active spiroketals. Photochemical ring expansion of these spirofused cyclobutanones in the presence of acetic acid or thiophenol gave 2-acetoxy- or 2-(thiophenoxy)-4-spirofused tetrahydrofurans. Elimination of the thiophenoxy group gave a 3,4-dihydrofuran that underwent Heck arylation and photochemical cycloaddition with chromium carbene complexes to give cyclobutanones.
RESUMO
The photochemical reaction between optically active ene carbamates and chromium alkoxycarbene complexes containing unsaturated aliphatic side chains was further developed. Although remote olefinic groups, including conjugated dienes, were tolerated, a homoallylic side chain underwent intramolecular reaction to give a strained cyclobutanone. (+)-Cerulenin was synthesized utilizing the photochemical reaction of an alkynylcarbene complex with an optically active ene carbamate and the bis(pi-crotyl)nickel halide alkylation of a vinyl bromide as key steps.
RESUMO
Photolysis of chromium carbene complexes in the presence of tertiary allylic amines resulted in a zwitterionic aza Cope rearrangement to produce unsaturated lactams in fair yield.