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1.
Chem Pharm Bull (Tokyo) ; 67(5): 397-403, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31061363

RESUMO

Cyano (CN) groups are equivalent to carbonyl as well as amino- and hydroxymethyl groups. Therefore, their catalytic introduction under metal catalysis is an important issue in synthetic organic chemistry. Ni-catalyzed hydrocyanation is one of the most well-investigated, powerful tools for installing a CN group. However, it is still difficult to control chemo- and regioselectivity. In this review, the author uses allenes to enable regio-, stereo-, and face-selective transformations to natural product synthesis and axial chirality transfer.


Assuntos
Alcadienos/síntese química , Produtos Biológicos/síntese química , Técnicas de Química Sintética/métodos , Níquel/química , Nitrilos/síntese química , Alcadienos/química , Produtos Biológicos/química , Catálise , Modelos Moleculares , Nitrilos/química , Estereoisomerismo
2.
Macromol Rapid Commun ; 40(2): e1800326, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30040146

RESUMO

Ring opening metathesis polymerization (ROMP) is a technique that allows the synthesis of well-defined linear polyolefins. Polymerization-induced self-assembly (PISA) involves the synthesis of amphiphilic block copolymers: a hydrophilic block is first polymerized homogeneously in solution (usually water) followed by polymerization of a second hydrophobic block, resulting in a diblock copolymer that self-assembles. In this communication, preliminary results of the development of PISA for the synthesis of amphiphilic block linear polyolefins via ROMP using a water-soluble PEGylated ruthenium alkylidene catalyst are presented. In the first step, a water-soluble modified-norbornene monomer was polymerized in water, then 1,5-cyclooctadiene was added to the system to produce amphiphilic block polyolefins. By varying the concentrations of hydrophilic versus hydrophobic monomer, stable latexes with final particles of ≈200 nm diameter were prepared.


Assuntos
Alcadienos/química , Técnicas de Química Sintética/métodos , Polimerização , Polímeros/química , Alcadienos/síntese química , Catálise , Interações Hidrofóbicas e Hidrofílicas , Microscopia Eletrônica de Transmissão , Modelos Químicos , Estrutura Molecular , Norbornanos/química , Polienos/síntese química , Polienos/química , Polietilenoglicóis/química , Polímeros/síntese química , Rutênio/química , Água/química
3.
J Am Chem Soc ; 140(50): 17428-17432, 2018 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-30521312

RESUMO

The cationic alkynyl Heck reaction between aryl triflates and alkynes to give substituted allenes is described. Key to the success of this method was the discovery and development of a new hybrid Pd(0)-catalyst, BobCat, that incorporates a water-soluble dba-ligand and biaryl phosphine ligand to provide substituted allenes in good yields under mild reaction conditions.


Assuntos
Alcadienos/síntese química , Alquinos/química , Complexos de Coordenação/química , Mesilatos/química , Catálise , Ligantes , Estrutura Molecular , Paládio/química , Água/química
4.
J Am Chem Soc ; 140(48): 16842-16854, 2018 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-30444358

RESUMO

The first broadly applicable strategy for SN2″-selective and enantioselective catalytic substitution is disclosed. Transformations are promoted by 5.0 mol% of a sulfonate-containing NHC-Cu complex (NHC = N-heterocyclic carbene), and are carried out in the presence of commercially available allenyl-B(pin) (pin = pinacolato) or a readily accessible silyl-protected propargyl-B(pin). Acyclic, or aryl-, heteroaryl-, and alkyl-substituted penta-2,4-dienyl phosphates, as well as those bearing either only 1,2-disubstituted olefins or a 1,2-disubstituted and a trisubstituted alkene were found to be suitable starting materials. Cyclic dienyl phosphates may also serve as substrates. The products containing, in addition to a 1,3-dienyl group, a readily functionalizable propargyl moiety (from reactions with allenyl-B(pin)) were obtained in 51-82% yield, 84-97% SN2″ selectivity, 89:11-97:3 E: Z ratio, and 86:14-98:2 enantiomeric ratio (er). Reactions with a silyl-protected propargyl-B(pin) compound led to the formation of the corresponding silyl-allenyl products in 53-89% yield, 69-96% SN2″ selectivity, 98:2 to >98:2 E: Z ratio, and 94:6-98:2 er. Insight regarding several of the unique mechanistic attributes of the catalytic process was obtained on the basis of kinetic isotope effect measurements and DFT studies. These investigations indicate that cationic π-allyl-Cu complexes are likely intermediates, clarifying the role of the s-cis and s-trans conformers of the intermediate organocopper species and their impact on E: Z selectivity and enantioselectivity. The utility of the approach is demonstrated by chemoselective functionalization of various product types, through which the propargyl, allenyl, or 1,3-dienyl sites within the products have been converted catalytically and chemoselectively to several useful derivatives.


Assuntos
Compostos de Boro/química , Complexos de Coordenação/química , Alcadienos/síntese química , Catálise , Cobre/química , Modelos Químicos , Estereoisomerismo , Ácidos Sulfônicos/química
5.
J Am Chem Soc ; 140(27): 8434-8438, 2018 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-29936839

RESUMO

Conjugated dienes and polyenes are typically synthesized by sequential introduction of C═C bonds. Here, we report a practical and scalable, catalytic dienylation that is highly regio- and stereoselective for both C═C bonds. The reaction is enabled by a stereoselective palladium-catalyzed cross-coupling that is preceded by a regioselective base-induced ring opening of readily available sulfolenes. The dienylation reaction is particularly useful for the synthesis of synthetically challenging dienes containing cis double bonds. We also show that the reaction can serve as a synthetic platform for the construction of conjugated polyenes.


Assuntos
Alcadienos/síntese química , Polienos/síntese química , Alcadienos/química , Catálise , Técnicas de Química Sintética/métodos , Paládio/química , Polienos/química , Estereoisomerismo
6.
ACS Comb Sci ; 20(5): 292-297, 2018 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-29620860

RESUMO

Under the acidic conditions, substituted furans were constructed from γ-alkynyl ketones through corresponding allene intermediates in one-pot. The methodology was also tailored to a series of the Ugi reaction products for the synthesis of 6-methylpyrazin-2(1 H)-one derivatives. The current method offered significant advantages for the combinatorial applications of these chemical scaffolds.


Assuntos
Ácidos/química , Alcadienos/síntese química , Furanos/síntese química , Cetonas/síntese química , Pirazinas/síntese química , Ciclização , Estereoisomerismo , Temperatura Ambiente
7.
J Am Chem Soc ; 140(7): 2446-2449, 2018 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-29420028

RESUMO

The synthesis of highly substituted 1,3-dienes from the coupling of vinyl bromides with vinyl triflates is reported for the first time. The coupling is catalyzed by a combination of (5,5'-bis(trifluoromethyl)-2,2'-bipyridine)NiBr2 and (1,3-bis(diphenylphosphino)propane)PdCl2 in the presence of a zinc reductant. This method affords tetra- and penta-substituted 1,3-dienes that would otherwise be difficult to access and tolerates electron-rich and -poor substituents, heterocycles, an aryl bromide, and a pinacol boronate ester. Mechanistically, the reaction appears to proceed by an unusual zinc-mediated transfer of a vinyl group between the nickel and palladium centers.


Assuntos
Alcadienos/síntese química , Níquel/química , Compostos Organometálicos/química , Paládio/química , Alcadienos/química , Catálise , Estrutura Molecular
8.
J Am Chem Soc ; 140(8): 2862-2868, 2018 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-29406705

RESUMO

The Diels-Alder (DA) reaction is a cornerstone of synthesis, yet Nature does not use catalysts for intermolecular [4+2] cycloadditions. Attempts to create artificial "Diels-Alderases" have also met with limited success, plagued by product inhibition. Using a simple Pd2L4 capsule we now show DA catalysis that combines efficient turnover alongside enzyme-like hallmarks. This includes excellent activity (kcat/kuncat > 103), selective transition-state stabilization comparable to the most proficient DA catalytic antibodies, and control over regio- and chemoselectivity that would otherwise be difficult to achieve using small-molecule catalysts. Unlike other catalytic approaches that use synthetic capsules, this method is not defined by entropic effects; instead multiple H-bonding interactions modulate reactivity, reminiscent of enzymatic action.


Assuntos
Alcadienos/síntese química , Compostos Organometálicos/química , Quinonas/química , Alcadienos/química , Catálise , Reação de Cicloadição , Estrutura Molecular
9.
J Am Chem Soc ; 139(45): 16064-16067, 2017 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-29058889

RESUMO

An accelerative asymmetric gold catalysis is achieved for the first time via chiral ligand metal cooperation. An asymmetrically positioned remote amide group in the designed chiral binaphthyl-based ligand plays the essential role of a general base catalyst and selectively accelerates the cyclizations of 4-allen-1-ols into one prochiral allene face. The reactions are mostly highly enantioselective with achiral substrates, and due to the accelerated nature of the catalysis catalyst loadings as low as 100 ppm are allowed. With a pre-existing chiral center at any of the backbone sp3-carbons, the reaction remained highly efficient and most importantly maintained excellent allene facial selectivities regardless of the substrate stereochemistry. By using different combinations of ligand and substrate enantiomers, it is now possible to access all four stereoisomers of versatile 2-vinyltetrahydrofurans with exceedingly high selectivity. The underpinning design of this chemistry reveals a novel and conceptually distinctive strategy to tackle challenging asymmetric gold catalysis, which to date has relied on decelerative asymmetric steric hindrance approaches.


Assuntos
Alcadienos/síntese química , Amidas/química , Ouro/química , Naftalenos/química , Alcadienos/química , Catálise , Ligantes , Estrutura Molecular
10.
Molecules ; 22(7)2017 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-28684715

RESUMO

In this study, in order to find novel biologically active penta-1,4-dien-3-one derivatives, a series of penta-1,4-dien-3-one compounds containing a substituted pyrazole subunit were designed and synthesized. Their structures were characterized by ¹H-NMR, 13C-NMR and elemental analysis. The preliminary bioassays displayed that most of the title compounds showed significant antiproliferative activity against HepG2 cell lines. Especially, compounds 7a-m, o, r, s, u, w, y and z were active against HepG2 cells with IC50 values of 0.10-5.05 µM, which were superior to that of the contrast sorafenib (IC50 = 16.20 µM).


Assuntos
Alcadienos/síntese química , Alcadienos/farmacologia , Pirazóis/química , Alcadienos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Curcumina/análogos & derivados , Curcumina/química , Desenho de Drogas , Humanos , Pirimidinas/química
11.
Eur J Med Chem ; 137: 263-279, 2017 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-28601720

RESUMO

To further engineer dienones with optimal combinations of potency and bioavailability, thirty-four asymmetric 1,5-diarylpenta-1,4-dien-3-ones (25-58) have been designed and synthesized for the evaluation of their in vitro anti-proliferative activity in three human prostate cancer cell lines and one non-neoplastic prostate epithelial cell line. All these asymmetric dienones are sufficiently more potent than curcumin and their corresponding symmetric counterparts. The optimal dienone 58, with IC50 values in the range of 0.03-0.12 µM, is 636-, 219-, and 454-fold more potent than curcumin in three prostate cancer cell models. Dienones 28 and 49 emerged as the most promising asymmetric dienones that warrant further preclinical studies. The two lead compounds demonstrated substantially improved potency in cell models and superior bioavailability in rats, while exhibiting no acute toxicity in the animals at the dose of 10 mg/kg. Dienones 28 and 46 can induce PC-3 cell cycle regulation at the G0/G1 phase. However, dienone 28 induces PC-3 cell death in a different way from 46 even though they share the same scaffold, indicating that terminal heteroaromatic rings are critical to the action of mechanism for each specific dienone.


Assuntos
Alcadienos/farmacologia , Antineoplásicos/farmacologia , Células Epiteliais/efeitos dos fármacos , Neoplasias da Próstata/tratamento farmacológico , Alcadienos/síntese química , Alcadienos/química , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células Epiteliais/patologia , Humanos , Masculino , Microssomos Hepáticos/efeitos dos fármacos , Estrutura Molecular , Neoplasias da Próstata/patologia , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade , Células Tumorais Cultivadas
12.
Angew Chem Int Ed Engl ; 56(6): 1520-1524, 2017 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-28079946

RESUMO

The rhodium-catalyzed atom-economic asymmetric N-selective intermolecular addition of purine derivatives to terminal allenes is reported. Branched allylic purines were obtained in high yields, regioselectivity and outstanding enantioselectivity utilizing a Rh/Josiphos catalyst. Conversely, linear selective allylation of purines could be realized in good to excellent regio- and E/Z-selectivity with a Pd/dppf catalyst system. Furthermore, the new methodology was applied to a straightforward asymmetric synthesis of carbocyclic nucleoside abacavir.


Assuntos
Compostos Alílicos/síntese química , Antirretrovirais/síntese química , Didesoxinucleosídeos/síntese química , Purinas/síntese química , Alcadienos/síntese química , Alcadienos/química , Compostos Alílicos/química , Antirretrovirais/química , Catálise , Didesoxinucleosídeos/química , Modelos Moleculares , Purinas/química , Ródio/química , Estereoisomerismo
13.
J Am Chem Soc ; 139(5): 1998-2005, 2017 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-28121128

RESUMO

Allenes are useful functional groups in synthesis as a result of their inherent chemical properties and established reactivity patterns. One property of chemical bonding renders 1,3-substituted allenes chiral, making them attractive targets for asymmetric synthesis. While there are many enantioselective methods to synthesize chiral allenes from chiral starting materials, fewer methods exist to directly synthesize enantioenriched chiral allenes from achiral precursors. We report here an asymmetric boronate addition to sulfonyl hydrazones catalyzed by chiral biphenols to access enantioenriched allenes in a traceless Petasis reaction. The resulting Mannich product from nucleophilic addition eliminates sulfinic acid, yielding a propargylic diazene that performs an alkyne walk to afford the allene. Two enantioselective approaches have been developed; alkynyl boronates add to glycolaldehyde imine to afford allylic hydroxyl allenes, and allyl boronates add to alkynyl imines to form 1,3-alkenyl allenes. In both cases, the products are obtained in high yields and enantioselectivities.


Assuntos
Alcadienos/síntese química , Ácidos Borônicos/química , Hidrazonas/química , Fenóis/química , Alcadienos/química , Catálise , Estrutura Molecular , Estereoisomerismo
14.
Org Biomol Chem ; 15(3): 584-588, 2017 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-27775130

RESUMO

1,3-Dienyl ß-keto esters are cyclised into bicyclolactones using the Bi(OTf)3/TfOH catalytic system. This reaction represents a rare case of simultaneous C-C and C-O bond formation at positions 1 and 3 of a 1,3-diene. Application to the synthesis of ramulosin is presented.


Assuntos
Alcadienos/síntese química , Ésteres/química , Cetonas/química , Mesilatos/química , Alcadienos/química , Catálise , Ciclização , Estrutura Molecular
15.
Acc Chem Res ; 49(11): 2444-2458, 2016 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-27797480

RESUMO

The rich chemistry of cyclobutanes is underpinned by a large body of synthetic literature devoted to their synthesis and decoration. This is motivated by the widespread representation of cyclobutane moieties in biologically active natural products and man-made molecules. Surprisingly, this vast array of knowledge finds no parallel in the chemistry of cyclobutenes, their unsaturated analogues. In particular, a dearth of methods to synthesize enantioenriched cyclobutenes is apparent upon cursory investigation of the literature. As a leading example, the photocycloaddition of maleic anhydride to acetylene or dichloroethylene, probably a benchmark of cyclobutene synthesis, delivers a meso cyclic anhydride which can be further converted to a cyclobutene product by enantioselective desymmetrization by ring opening. Nonetheless, such an approach delivers products with a rather inflexible substitution pattern around the four-membered ring. The lack of general approaches has motivated our group and others to develop novel routes to cyclobutene scaffolds, leading to the development of a strategy that combines photochemistry and catalysis. Indeed, we have coupled the simple and efficient photochemical isomerization of 2-pyrone into a strained bicyclo[2.2.0] lactone with palladium-catalyzed allylic alkylation as a simple and versatile access to functionalized cyclobutenes. Several nucleophiles can be added to the activated, strained intermediate, including malonate anions and azlactones. The products are mono- and bicyclic building blocks richly decorated with functional groups. Importantly, they are formed with high levels of diastereoselectivity as expected by the tenets of palladium-catalyzed allylic alkylation, which posit that the oxidative addition and nucleophilic capture steps proceed with inversion of configuration, resulting in overall retention (inversion + inversion). However, the transposition of the methodology to an asymmetric version subsequently led to the surprising discovery of a family of highly enantioselective, diastereodivergent catalytic processes. Indeed, we observed a ligand-dependent stereochemical outcome for a range of palladium-catalyzed allylic alkylations affording either overall retention or overall inversion of configuration, and that with very high levels of enantio- and diastereoselectivity. The new family of diastereodivergent reactions enables the conversion of the aforementioned racemic bicyclo[2.2.0] lactone into each of 4 stereoisomeric products, at will. Although the mechanistic details at the origin of this unusual stereodivergence are not yet fully elucidated, it became clear through our studies that unique Pd-allyl complexes, residing preferentially as their σ-(monohapto)-bound isomers, are at the heart of the process. The cyclobutenes prepared can also engage in electrocyclic ring-opening reactions (often spontaneous depending on the substitution pattern) that link this chemistry with that of diene and polyene frameworks. Using the strategies laid out above, our group was then able to harness the high stereospecificity of electrocyclic reactions and design modular syntheses of several natural products and natural product fragments. We believe that the methods presented herein shall soon pave the way for the streamlined synthesis of more complex polyenic natural products.


Assuntos
Alcadienos/síntese química , Ciclobutanos/química , Ciclobutanos/síntese química , Paládio/química , Alquilação , Compostos Bicíclicos Heterocíclicos com Pontes/química , Catálise , Complexos de Coordenação/química , Lactonas/química , Ligantes , Estereoisomerismo , Zinco/química
16.
Org Lett ; 18(6): 1230-3, 2016 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-26925611

RESUMO

Chiral ammonium salts were used to catalyze the isomerization of organomanganese-complexed alkynyl aldehydes to chiral allenal building blocks in moderate to good enantiomeric excesses. Normally, conjugated alkynyl aldehydes do not isomerize to their thermodynamically less stable allene isomers. However, with a manganese auxiliary in place to promote allene formation, asymmetric protonation of cumulenolate intermediates was realized using a variety of cinchonidinium salts in a weakly basic biphasic reaction system. Optimal results were realized using a novel cinchonidinium geranyl derivative with its C-9 hydroxyl group playing a crucial role in enantioselectivity.


Assuntos
Aldeídos/química , Alcadienos/síntese química , Manganês/química , Compostos Organometálicos/química , Aldeídos/síntese química , Alcadienos/química , Catálise , Técnicas de Química Combinatória , Hidrogenação , Estrutura Molecular , Estereoisomerismo , Relação Estrutura-Atividade
17.
Chem Asian J ; 11(3): 330-41, 2016 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-26395547

RESUMO

Axially, planar, and helical chiral compounds are indispensable building blocks in modern organic synthesis. A wide variety of chiral ligands and catalysts were designed based on these chiral scaffolds, and these chiral ligands and catalysts were used for various catalytic asymmetric transformations to produce important chiral compounds in an optically enriched form. Furthermore, these chiral skeletons are found in the structure of biologically active natural products. Thus, the development of efficient enantioselective methods for the synthesis of these chiral compounds is an important task in the field of organic chemistry. In the last few years, organocatalyzed approaches, which are one of the most reliable catalytic asymmetric methods, became a hot topic. This Focus Review summarizes asymmetric organocatalytic methods for the synthesis of axially, planar, and helical chiral compounds as useful chiral building blocks.


Assuntos
Compostos Orgânicos/química , Alcadienos/síntese química , Alcadienos/química , Anilidas/síntese química , Anilidas/química , Benzamidas/síntese química , Benzamidas/química , Produtos Biológicos/síntese química , Produtos Biológicos/química , Catálise , Cinética , Ligantes , Compostos Orgânicos/síntese química , Estereoisomerismo
18.
ACS Comb Sci ; 17(11): 658-62, 2015 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-26521847

RESUMO

Development of the self-assembled monolayer/MALDI mass spectrometry (SAMDI) platform to enable a high-throughput optimization of a traceless Petasis reaction is described. More than 1800 unique reactions were conducted simultaneously on an array of self-assembled monolayers of alkanethiolates on gold to arrive at optimized conditions, which were then successfully transferred to the solution phase. The utility of this reaction was validated by the efficient synthesis of a variety of di- and trisubstituted allenes.


Assuntos
Alcadienos/síntese química , Alcanos/química , Ouro/química , Ensaios de Triagem em Larga Escala , Compostos de Sulfidrila/química , Alcadienos/química , Técnicas de Química Combinatória , Estrutura Molecular , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
19.
Org Lett ; 17(22): 5558-61, 2015 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-26517569

RESUMO

The total synthesis of the natural product depudecin, an antiangiogenic microbial polyketide with inhibitory activity against histone deacetylases, is reported. Characterized by a highly oxidized 11-carbon chain containing two epoxides conjugated through a trans-disubstituted olefin, its total synthesis was efficiently accomplished by a novel asymmetric methodology of epoxide formation based on a new class of chiral sulfonium salts, allowing for the construction of the oxirane rings in an efficient and stereoselective fashion.


Assuntos
Alcadienos/síntese química , Produtos Biológicos/síntese química , Compostos de Epóxi/síntese química , Álcoois Graxos/síntese química , Alcadienos/química , Alcenos , Alternaria/química , Compostos de Epóxi/química , Álcoois Graxos/química , Estrutura Molecular , Oxirredução , Estereoisomerismo
20.
J Org Chem ; 80(22): 11388-97, 2015 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-26514061

RESUMO

Visible-light photoreductive coupling of 2-arylallyl bromides in the presence of the photocatalyst Ru(bpy)3(PF6)2, a Hantzsch ester, and i-Pr2NEt gives 2,5-diaryl-1,5-dienes in high yield. This method avoids the use of stoichiometric metal reductants and is compatible with the presence of halogen, alkyl, electron-donating, and electron-withdrawing substituents on the aromatic ring.


Assuntos
Alcadienos/síntese química , Compostos Alílicos/química , Brometos/química , Compostos Organometálicos/química , Alcadienos/química , Catálise , Luz , Estrutura Molecular , Oxirredução , Processos Fotoquímicos
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