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1.
Molecules ; 26(5)2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33800380

RESUMO

Studies on a one-pot synthesis of novel multisubstituted 1-alkoxyindoles 1 and their mechanistic investigations are presented. The synthesis of 1 was successfully achieved through consecutive four step reactions from substrates 2. The substrates 2, prepared through a two-step synthetic sequence, underwent three consecutive reactions of nitro reduction, intramolecular condensation, and nucleophilic 1,5-addition to provide the intermediates, 1-hydroxyindoles 8, which then were alkylated in situ with alkyl halide to afford the novel target products 1. We optimized the reaction conditions for 1 focusing on the alkylation step, along with the consideration of formation of intermediates 8. The optimized condition was SnCl2·2H2O (3.3 eq) and alcohols (R1OH, 2.0 eq) for 1-2 h at 40 °C and then, base (10 eq) and alkyl halides (R2Y, 2.0 eq) for 1-4 h at 25-50 °C. Notably, all four step reactions were performed in one-pot to give 1 in good to modest yields. Furthermore, the mechanistic aspects were also discussed regarding the reaction pathways and the formation of side products. The significance lies in development of efficient one-pot reactions and in generation of new 1-alkoxyindoles.


Assuntos
Álcoois/síntese química , Indóis/síntese química , Álcoois/química , Alquilação , Ciclização , Estrutura Molecular , Estereoisomerismo , Compostos de Estanho
2.
Nat Chem ; 13(4): 312-318, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33603222

RESUMO

Enzymatic reactions through mononuclear metal hydrides are unknown in nature, despite the prevalence of such intermediates in the reactions of synthetic transition-metal catalysts. If metalloenzymes could react through abiotic intermediates like these, then the scope of enzyme-catalysed reactions would expand. Here we show that zinc-containing carbonic anhydrase enzymes catalyse hydride transfers from silanes to ketones with high enantioselectivity. We report mechanistic data providing strong evidence that the process involves a mononuclear zinc hydride. This work shows that abiotic silanes can act as reducing equivalents in an enzyme-catalysed process and that monomeric hydrides of electropositive metals, which are typically unstable in protic environments, can be catalytic intermediates in enzymatic processes. Overall, this work bridges a gap between the types of transformation in molecular catalysis and biocatalysis.


Assuntos
Anidrase Carbônica II/química , Hidrogênio/química , Cetonas/química , Silanos/química , Zinco/química , Álcoois/síntese química , Biocatálise , Anidrase Carbônica II/metabolismo , Humanos , Cetonas/metabolismo , Modelos Químicos , Simulação de Acoplamento Molecular , Oxirredução , Ligação Proteica , Estereoisomerismo
3.
Adv Exp Med Biol ; 1195: 189-198, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32468477

RESUMO

In the present work, new indole derivatives, i.e., 5-[N,N-di alkyl amino alkoxy] azaindole 2,3- di-one derivatives, are synthesized and characterized. These compounds were subjected to acute toxicity and then screened for antiepileptic activity on maximal electroshock seizure (MES) model in albino Wistar rats. In that study 5-[2-dimethyl amino ethoxy] Azaindole-3-hydrazone,2-one and 5-[2- dimethyl amino ethoxy] Azaindole 2-one,3-thiothiosemicarbazone(IIIa) showed good antiepileptic activity and less neurotoxicity compared to phenytoin. The purpose of the present study is to investigate the effect of 5-[2-dimethyl amino ethoxy] Indole 2,3- di one and 5-[2-dimethyl amino ethoxy] Azaindole 2-one,3-thiosemicarbazone(IIIa) derivatives on biogenic amines concentrations in rat brain after induction of seizures by MES method. The aim of study was relationship between seizure activities and altered the monoamines such as Noradrenaline (NA), Dopamine (DA), Serotonin (5-HT) in forebrain of rats in MES seizure models. In MES model, study of 5-[2-dimethyl amino ethoxy] Azaindole 3-hydrazone,2-one(Va) and 5-[2-dimethyl amino ethoxy]Azaindole 2-one,3-thiosemicarbazone(IIIa) (100 mg/kg) showed significant restoration of the decreased levels of brain monoamines such as noradrenaline, dopamine, and 5-hydroxytryptamine. Thus, this study suggests that 5-[2-Dimethyl amino ethoxy] Azaindole 3-hydrazone,2-one (V) and 5-[2-dimethyl amino ethoxy] Azaindole 2-one,3-thiosemicarbazone (IIIa) increased the monoamines on rat brain, which may decrease the susceptibility to MES-induced seizure in rats.


Assuntos
Anticonvulsivantes/síntese química , Anticonvulsivantes/uso terapêutico , Indóis/síntese química , Indóis/uso terapêutico , Tiossemicarbazonas/síntese química , Tiossemicarbazonas/uso terapêutico , Álcoois/síntese química , Álcoois/química , Álcoois/farmacologia , Álcoois/uso terapêutico , Animais , Anticonvulsivantes/química , Anticonvulsivantes/farmacologia , Modelos Animais de Doenças , Hidrazonas/síntese química , Hidrazonas/química , Hidrazonas/farmacologia , Hidrazonas/uso terapêutico , Indóis/química , Indóis/farmacologia , Ratos , Ratos Wistar , Convulsões/tratamento farmacológico , Tiossemicarbazonas/química , Tiossemicarbazonas/farmacologia
4.
Org Biomol Chem ; 18(7): 1279-1336, 2020 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-32025682

RESUMO

Enantio- and diastereodivergent routes to marine-origin natural products with different sizes of cyclic ethers and lactones have been used in order to assign stereochemical features. Kainoid amino acids such as isodomoic acids have been synthesized using diastereodivergent routes. The bis(indole) alkaloid dragmacidin F has been prepared by enantiodivergent strategies as well as furanoterpenes and the tetracyclic agelastatin A. Natural products containing five-membered lactones like quercus lactones, muricatacins, goniofufuranones, methylenolactocins and frenolicin B have been synthesized using stereodivergent routes. Macrolides are very abundant lactones and have been mainly prepared from the corresponding seco-acids by lactonization, such as lasiodiplodin, zaeralanes, macrosphelides and haloprins, or by ring-closing metathesis, such as aspercyclides, microcarpalides, macrolides FD-891 and 892, and tetradic-5-en-9-olides. Other natural products including cyclic ethers (such as sesamin, asarinin, acetogenins, centrolobines and nabilones), alcohols (such as sulcatol), esters (such as methyl jasmonates), polycyclic precursors of fredericamycin, amino alcohols (such as ambroxol and sphingosines), isoprostanes, isofurans, polyketide precursors of anachelins, brevicomins, gummiferol, shikimic acid and the related compounds, and the pheromone disparlure have been synthesized stereodivergently. Heterocyclic systems such as epoxides, theobroxides and bromoxones, oxetan-3-ones, 5- to 8-membered cyclic ethers, azetidones, γ-lactams, oxazolidinones, bis(oxazolines), dihydropyridoisoindolines and octahydroisoquinolines have been prepared following stereodivergent routes. Stereodivergent routes to unnatural compounds such as alkenes, dienes, allenes, cyclopropanes, alcohols, aldols, amines, amino alcohols, ß-amino acids, carboxylic acids, lactones, nitriles and α-amino nitriles have been considered as well.


Assuntos
Produtos Biológicos/síntese química , Compostos Heterocíclicos/síntese química , Lactonas/síntese química , Álcoois/síntese química , Álcoois/química , Alcenos/síntese química , Alcenos/química , Aminas/síntese química , Aminas/química , Aminoácidos/síntese química , Aminoácidos/química , Produtos Biológicos/química , Ácidos Carboxílicos/síntese química , Ácidos Carboxílicos/química , Compostos Heterocíclicos/química , Lactonas/química , Estrutura Molecular , Nitrilas/síntese química , Nitrilas/química , Estereoisomerismo
5.
Chem Rev ; 120(3): 1513-1619, 2020 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-31904936

RESUMO

This review describes the additions of allylmagnesium reagents to carbonyl compounds and to imines, focusing on the differences in reactivity between allylmagnesium halides and other Grignard reagents. In many cases, allylmagnesium reagents either react with low stereoselectivity when other Grignard reagents react with high selectivity, or allylmagnesium reagents react with the opposite stereoselectivity. This review collects hundreds of examples, discusses the origins of stereoselectivities or the lack of stereoselectivity, and evaluates why selectivity may not occur and when it will likely occur.


Assuntos
Álcoois/síntese química , Aldeídos/química , Compostos Alílicos/química , Cetonas/química , Magnésio/química , Compostos Organometálicos/química , Estereoisomerismo
6.
J Vis Exp ; (152)2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31680684

RESUMO

Caged compounds enable the photo-mediated manipulation of the cell physiology with high spatiotemporal resolution. However, the limited structural diversity of currently available caging groups and the difficulties in synthetic modification without sacrificing their photolysis efficiencies are obstacles to expanding the repertoire of caged compounds for live cell applications. As the chemical modification of coumarin-type photo-caging groups is a promising approach for the preparation of caged compounds with diverse physical and chemical properties, we report a method for the synthesis of clickable caged compounds that can be modified easily with various functional units via the copper(I)-catalyzed Huisgen cyclization. The modular platform molecule contains a (6-bromo-7-hydroxycoumarin-4-yl)methyl (Bhc) group as a photo-caging group, which exhibits a high photolysis efficiency compared to those of the conventional 2-nitrobenzyls. General procedures for the preparation of clickable caged compounds containing amines, alcohols, and carboxylates are presented. Additional properties such as the water solubility and cell targeting ability can be readily incorporated into clickable caged compounds. Furthermore, the physical and photochemical properties, including the photolysis quantum yield, were measured and were found to be superior to those of the corresponding Bhc caged compounds. The described protocol could therefore be considered a potential solution for the lack of structural diversity in the available caged compounds.


Assuntos
Cumarínicos/síntese química , Imagem Óptica/métodos , Processos Fotoquímicos , Fotólise , Álcoois/análise , Álcoois/síntese química , Animais , Células CHO , Ácidos Carboxílicos/análise , Ácidos Carboxílicos/síntese química , Cumarínicos/análise , Cricetinae , Cricetulus , Solubilidade
7.
Angew Chem Int Ed Engl ; 58(40): 14245-14249, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31390474

RESUMO

A hybrid transition-metal/radical process is described that results in the addition of organozinc reagents and alkyl halides across alkenyl boron reagents in an enantioselective catalytic fashion. The reaction can be accomplished both intermolecularly and intramolecularly, providing useful product yields and high enantioselectivities in both manifolds.


Assuntos
Álcoois/síntese química , Compostos de Boro/química , Hidrocarbonetos Iodados/química , Compostos Organometálicos/química , Zinco/química , Álcoois/química , Radicais Livres/química , Estrutura Molecular , Estereoisomerismo
8.
J Am Chem Soc ; 141(36): 14136-14141, 2019 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-31465211

RESUMO

The first catalytic enantioselective carbonyl (α-amino)allylations are described. Phthalimido-allene 1 and primary alcohols 2a-2z, 2a'-2c' engage in hydrogen auto-transfer-mediated carbonyl reductive coupling by way of (α-amino)allyliridium-aldehyde pairs to form vicinal amino alcohols 3a-3z, 3a'-3c' with high levels of regio-, anti-diastereo-, and enantioselectivity. Reaction progress kinetic analysis and isotopic labeling studies corroborate a catalytic cycle involving turnover-limiting alcohol dehydrogenation followed by rapid allene hydrometalation.


Assuntos
Álcoois/química , Álcoois/síntese química , Alcadienos/química , Hidrogênio/química , Irídio/química , Ftalimidas/química , Catálise , Estrutura Molecular , Oxirredução
9.
J Am Chem Soc ; 141(34): 13625-13634, 2019 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-31329459

RESUMO

Enantioselective catalysis of excited-state photoreactions remains a substantial challenge in synthetic chemistry, and intermolecular photoreactions have proven especially difficult to conduct in a stereocontrolled fashion. Herein, we report a highly enantioselective intermolecular [2 + 2] cycloaddition of 3-alkoxyquinolones catalyzed by a chiral hydrogen-bonding iridium photosensitizer. Enantioselectivities as high as 99% ee were measured in reactions with a range of maleimides and other electron-deficient alkene reaction partners. An array of kinetic, spectroscopic, and computational studies supports a mechanism in which the photocatalyst and quinolone form a hydrogen-bonded complex to control selectivity, yet upon photoexcitation of this complex, energy transfer sensitization of maleimide is preferred. The sensitized maleimide then reacts with the hydrogen-bonded quinolone-photocatalyst complex to afford a highly enantioenriched cycloadduct. This finding contradicts a long-standing tenet of enantioselective photochemistry that held that stereoselective photoreactions require strong preassociation to the sensitized substrate in order to overcome the short lifetimes of electronically excited organic molecules. This system therefore suggests that a broader range of alternate design strategies for asymmetric photocatalysis might be possible.


Assuntos
Alcenos/química , Irídio/química , Maleimidas/química , Quinolonas/química , Álcoois/síntese química , Álcoois/química , Alcenos/síntese química , Catálise , Reação de Cicloadição/métodos , Transferência de Energia , Ligação de Hidrogênio , Maleimidas/síntese química , Processos Fotoquímicos , Quinolonas/síntese química , Estereoisomerismo
10.
Bioconjug Chem ; 30(7): 1969-1978, 2019 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-31251559

RESUMO

The ortho-hydroxy-protected aryl sulfate (OHPAS) linker is composed of a diaryl sulfate backbone equipped with a latent phenol moiety at the ortho position of one of the aryl units. The Ar-OH released when the ortho phenol undergoes intramolecular cyclization and displaces the second aryl unit can be viewed as a payload. We have shown in the preceding paper that the OHPAS linkers are highly stable chemically and in various plasmas, yet release payloads when exposed to suitable triggering conditions. As an extension of the OHPAS system, we employed a para-hydroxy benzyl (PHB) spacer for coupling to nonphenolic payloads; this tactic again provided a highly stable system capable of smooth release of appended payloads. The PHB modification works beautifully for tertiary amine and N-heterocycle payloads.


Assuntos
Aminas/química , Compostos de Benzil/química , Compostos Heterocíclicos/química , Fenol/química , Sulfatos/química , Álcoois/síntese química , Álcoois/química , Aminas/síntese química , Compostos de Benzil/síntese química , Ciclização , DNA/síntese química , DNA/química , Compostos Heterocíclicos/síntese química , Fenol/síntese química , RNA/síntese química , RNA/química , Sulfatos/síntese química
11.
Nat Chem ; 11(6): 571-577, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30988418

RESUMO

One of the core barriers to developing C-H activation reactions is the ability to distinguish between multiple C-H bonds that are nearly identical in terms of electronic properties and bond strengths. Through recognition of distance and molecular geometry, remote C(sp2)-H bonds have been selectively activated in the presence of proximate ones. Yet achieving such unconventional site selectivity with C(sp3)-H bonds remains a paramount challenge. Here we report a combination of a simple pyruvic acid-derived directing group and a 2-pyridone ligand that enables the preferential activation of the distal γ-C(sp3)-H bond over the proximate ß-C(sp3)-H bonds for a wide range of alcohol-derived substrates. A competition experiment between the five- and six-membered cyclopalladation step, as well as kinetic experiments, demonstrate the feasibility of using geometric strain to reverse the conventional site selectivity in C(sp3)-H activation.


Assuntos
Álcoois/química , Carbono/química , Técnicas de Química Sintética/métodos , Hidrogênio/química , Álcoois/síntese química , Derivados de Benzeno/síntese química , Ciclização , Estrutura Molecular , Compostos Organometálicos/síntese química , Paládio/química , Piridonas/química , Piruvatos/química
12.
Molecules ; 24(7)2019 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-30974778

RESUMO

In solid-phase organic synthesis, Wang resin is traditionally used for the immobilization of acids, alcohols, phenols, and amines. We report the use of Wang resin for the traceless synthesis of ketones via acid-labile enol ethers. We demonstrate the practicality of this synthetic strategy on the solid-phase synthesis of pyrrolidine-2,4-diones, which represent the core structure of several natural products, including tetramic acid. Base-triggered condensation of pyrrolidine-2,4-diones yielded 4-hydroxy-1,1',2',5-tetrahydro-2H,5'H-[3,3'-bipyrrole]-2,5'-diones.


Assuntos
Álcoois , Cetonas , Álcoois/síntese química , Álcoois/química , Aminas/química , Cetonas/síntese química , Cetonas/química
13.
J Am Chem Soc ; 141(16): 6726-6739, 2019 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-30943023

RESUMO

Historically accessed through two-electron, anionic chemistry, ketones, alcohols, and amines are of foundational importance to the practice of organic synthesis. After placing this work in proper historical context, this Article reports the development, full scope, and a mechanistic picture for a strikingly different way of forging such functional groups. Thus, carboxylic acids, once converted to redox-active esters (RAEs), can be utilized as formally nucleophilic coupling partners with other carboxylic derivatives (to produce ketones), imines (to produce benzylic amines), or aldehydes (to produce alcohols). The reactions are uniformly mild, operationally simple, and, in the case of ketone synthesis, broad in scope (including several applications to the simplification of synthetic problems and to parallel synthesis). Finally, an extensive mechanistic study of the ketone synthesis is performed to trace the elementary steps of the catalytic cycle and provide the end-user with a clear and understandable rationale for the selectivity, role of additives, and underlying driving forces involved.


Assuntos
Álcoois/química , Álcoois/síntese química , Aminas/química , Aminas/síntese química , Cetonas/química , Cetonas/síntese química , Técnicas de Química Sintética , Radicais Livres/química
14.
Org Lett ; 21(7): 2204-2208, 2019 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-30892050

RESUMO

Asymmetric reduction of hydroxynaphthoquinones to secondary metabolites, (3 S,4 R)-3,4,8- and (2 S,4 R)-2,4,8-trihydroxy-1-tetralone, a putative biosynthetic diketo intermediate and a probable natural analogue, (3 S,4 R)-7-acetyl-3,4,8-trihydroxy-6-methyl-3,4-dihydronaphthalene-1(2 H)-one, using NADPH-dependent tetrahydroxynaphthalene reductase (T4HNR) of Magnaporthe grisea is described. This work implies the involvement of T4HNR or related enzymes during the (bio)synthesis of other dihydroarenediols by reduction of the hydroxynaphthoquinone scaffold containing substrates.


Assuntos
Álcoois/síntese química , Proteínas Fúngicas/biossíntese , Magnaporthe/química , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/biossíntese , Proteínas Fúngicas/química , Estrutura Molecular , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/química
15.
Artigo em Inglês | MEDLINE | ID: mdl-30853700

RESUMO

Biological homochirality, such as that of l-amino acids, has been a puzzle with regards to the chemical origin of life. Asymmetric autocatalysis is a reaction in which a chiral product acts as an asymmetric catalyst to produce more of itself in the same absolute configuration. 5-Pyrimidyl alkanol was found to act as an asymmetric autocatalyst in the enantioselective addition of diisopropylzinc to pyrimidine-5-carbaldehyde. Asymmetric autocatalysis of 2-alkynyl-5-pyrimidyl alkanol with an extremely low enantiomeric excess of ca. 0.00005% exhibited significant asymmetric amplification to afford the same pyrimidyl alkanol with >99.5% enantiomeric excess and with an increase in the quantity of the same compound. We have employed asymmetric autocatalysis to examine the origin of homochirality. Asymmetric autocatalysis triggered by circularly polarized light, chiral minerals such as quartz, chiral organic crystals composed of achiral compounds gave highly enantioenriched pyrimidyl alkanol with absolute configurations corresponding with those of the chiral triggers. Absolute asymmetric synthesis without the intervention of any chiral factor was achieved. Chiral isotopomers acted as chiral triggers of asymmetric autocatalysis.


Assuntos
Álcoois/síntese química , Aldeídos/síntese química , Pirimidinas/síntese química , Alcinos/química , Catálise , Estereoisomerismo , Compostos de Zinco/química
16.
Bioorg Chem ; 86: 494-500, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30780018

RESUMO

Bromodomain PHD finger transcription factor (BPTF), a bromodomain-containing protein, plays a crucial role in the regulation of downstream gene expression through the specific recognition of lysine acetylation on bulk histones. The dysfunction of BPTF is closely involved with the development and progression of many human diseases, especially cancer. Therefore, BPTF bromodomain has become a promising drug target for epigenetic cancer therapy. However, unlike BET family inhibitors, few BPTF bromodomain inhibitors have been reported. In this study, by integrating docking-based virtual screening with biochemical analysis, we identified a novel selective BPTF bromodomain inhibitor DCB29 with the IC50 value of 13.2 ±â€¯1.6 µM by homogenous time-resolved fluorescence resonance energy transfer (HTRF) assays. The binding between DCB29 and BPTF was confirmed by NMR and SPR. Molecular docking disclosed that DCB29 occupied the pocket of acetylated H4 peptide substrate and provided detailed SAR explanations for its derivatives. Collectively, DCB29 presented great potential as a powerful tool for BPTF-related biological research and further medicinal chemistry optimization.


Assuntos
Álcoois/farmacologia , Benzamidas/farmacologia , Descoberta de Drogas , Fatores de Transcrição/antagonistas & inibidores , Álcoois/síntese química , Álcoois/química , Benzamidas/síntese química , Benzamidas/química , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Transferência Ressonante de Energia de Fluorescência , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Domínios Proteicos/efeitos dos fármacos , Relação Estrutura-Atividade , Fatores de Transcrição/isolamento & purificação , Fatores de Transcrição/metabolismo
17.
Crit Rev Biotechnol ; 39(3): 366-379, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30700159

RESUMO

Alcohol dehydrogenases are a group of oxidoreductases that specifically use NAD(P)+ or NAD(P)H as cofactors for electron acceptance or donation and catalyze interconversion between alcohols and corresponding carbonyl compounds. In addition to their physiological roles in metabolizing alcohols and aldehydes or ketones, alcohol dehydrogenases have received considerable attention with respect to their symmetry-breaking traits in catalyzing asymmetric reactions and have Accordingly, they have become widely applied in fine chemical synthesis, particularly in the production of chiral alcohols and hydroxyl compounds that are key elements in the synthesis of active pharmaceutical ingredients (API) employed in the pharmaceutical industry. The application of structural bioinformatics to the study of functional enzymes and recent scientific breakthroughs in modern molecular biotechnology provide us with an effective alternative to gain an understanding of the molecular mechanisms involved in asymmetric bioreactions and in overcoming the limitations of enzyme availability. In this review, we discuss molecular mechanisms underlying alcohol dehydrogenase-mediated asymmetric reactions, based on protein structure-function relationships from domain structure to functional active sites. The molecular principles of the catalytic machinery involving stereochemical recognition and molecular interaction are also addressed. In addition, the diversity of enzymatic functions and properties, for example, enantioselectivity, substrate specificity, cofactor dependence, metal requirement, and stability in terms of organic solvent tolerance and thermostability, are also discussed and based on a comparative analysis of high-resolution 3 D structures of representative alcohol dehydrogenases.


Assuntos
Álcool Desidrogenase/química , Biotecnologia/tendências , Biologia Computacional/tendências , Conformação Proteica , Álcool Desidrogenase/genética , Álcoois/síntese química , Álcoois/química , Sequência de Aminoácidos/genética , Biotransformação/genética , Catálise , Humanos , Relação Estrutura-Atividade
18.
J Am Chem Soc ; 141(5): 1828-1832, 2019 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-30693768

RESUMO

The first intermolecular carbonyl arylations via transfer hydrogenative reductive coupling are described. Using rhodium catalysts modified by tBu2PMe, sodium formate-mediated reductive coupling of aryl iodides with aldehydes occurs in a chemoselective fashion in the presence of protic functional groups and lower halides. This work expands the emerging paradigm of transfer hydrogenative coupling as an alternative to pre-formed carbanions or metallic reductants in C═X addition.


Assuntos
Álcoois/síntese química , Aldeídos/química , Formiatos/química , Substâncias Redutoras/química , Ródio/química , Álcoois/química , Catálise , Hidrogenação , Estrutura Molecular , Estereoisomerismo
19.
J Am Chem Soc ; 141(5): 1823-1827, 2019 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-30693771

RESUMO

Transition-metal-catalyzed addition of aryl halides across carbonyls remains poorly developed, especially for aliphatic aldehydes and hindered substrate combinations. We report here that simple nickel complexes of bipyridine and PyBox can catalyze the addition of aryl halides to both aromatic and aliphatic aldehydes using zinc metal as the reducing agent. This convenient approach tolerates acidic functional groups that are not compatible with Grignard reactions, yet sterically hindered substrates still couple in high yield (33 examples, 70% average yield). Mechanistic studies show that an arylnickel, and not an arylzinc, adds efficiently to cyclohexanecarboxaldehyde, but only in the presence of a Lewis acid co-catalyst (ZnBr2).


Assuntos
Álcoois/síntese química , Aldeídos/química , Hidrocarbonetos Bromados/química , Níquel/química , Álcoois/química , Catálise , Estrutura Molecular
20.
Chem Pharm Bull (Tokyo) ; 67(1): 1-17, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30606946

RESUMO

This review reports on the development of new synthetic methods using oxiranyl anions and their application to the synthesis of polycyclic ether marine natural products. Novel iterative and convergent methods for large, complex polycyclic ether structures have been devised. In these, the reactions of sulfonyl-stabilized oxiranyl anions were employed to construct trans-fused polyether ring systems, along with 6-endo cyclization and ring expansion reactions. Total syntheses of polycyclic ether marine toxins, viz. hemibrevetoxin B, gambierol, and gymnocin-A, were achieved based on the oxiranyl anion strategy developed.


Assuntos
Álcoois/química , Produtos Biológicos/síntese química , Éteres/síntese química , Compostos Policíclicos/síntese química , Álcoois/síntese química , Ânions/síntese química , Ânions/química , Produtos Biológicos/química , Compostos de Epóxi/química , Éteres/química , Conformação Molecular , Compostos Policíclicos/química
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