Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 31
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Org Lett ; 25(31): 5890-5895, 2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37530173

RESUMO

Herein, we reported an effective selective nucleophilic cyclization/cross-coupling cascade reaction of N-tosyl ortho-alkynylanilines and N-acyl ortho-alkynylanilines using Rh(COD)2BF4/tBuXantPhos as a catalyst. The present protocol features excellent chemo- and regioselectivity, high atom-economy, and a broad range of substrates. The mechanism studies indicated that the key to the success of this reaction is the powerful capacity of the rhodium catalyst to recognize the N-substituent group in the selective nucleophilic cyclization and selective alkyne insertion.

2.
Org Lett ; 24(47): 8603-8608, 2022 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-36403156

RESUMO

A chiral Lewis base catalyzed enantioselective N-allylic alkylation of 2-hydroxypyridines and MBH carbonates is documented, affording a convenient access to N-alkylated 2-pyridones with up to 99% ee and 99% yield. Experimental and computational studies have revealed that the strong hydrogen bond interaction between the chiral Lewis base catalyst and 2-hydroxypyridines plays a crucial role in this reaction for the reactivity, chemoselectivity, and enantioselectivity.


Assuntos
Bases de Lewis , Piridonas , Alquilação , Ligação de Hidrogênio
3.
Org Lett ; 24(36): 6489-6493, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36069728

RESUMO

An effective strategy for the ring-opening/elaboration of cyclopropanes by phosphine catalyst is documented, providing the 2,4-pentadiene sulfonamides and isoindolines in moderate to good yields. The key to the success of this reaction is phosphine-catalyzed introduction of a trigonal center into cyclopropanes, which results in the formation of higher ring strain cyclopropylidenemethyl phosphonium salt. Moreover, this methodology is employed as the key step for the synthesis of bioactive molecules.

4.
Chem Sci ; 13(34): 10095-10102, 2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36128232

RESUMO

Herein, we disclosed a novel and efficient palladium-catalyzed nucleomethylation of alkynes for the simultaneous construction of the heteroaromatic ring and methyl group. The 3-methylindoles, 3-methylbenzofurans and 4-methylisoquinolines were obtained in moderate to excellent yields. Notably, this methodology was employed as a key step for synthesis of a pregnane X receptor antagonist, zindoxifene, bazedoxifene and AFN-1252. The kinetic studies revealed that reductive elimination might be the rate-determining step.

5.
Org Lett ; 24(3): 864-868, 2022 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-35023743

RESUMO

Palladium-catalyzed regioselective α-amino C-H functionalization via the isomerization of α,ß-unsaturated carbonyls including esters, ketones, and amides has been established, providing an easy access to a wide array of tricyclic 1,2,3,4-tetrahydro-b-carbolines, azepinoindoles, 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles, 4,5,6,7-tetrahydro-1H-pyrrolo[2,3-c]pyridines, 1,2,3,4-tetrahydropyrazino-[1,2-a]indoles, pyran-fused indoles, and tetrahydroisoquinolines in good to excellent yields. This transformation showed high regioselectivity, excellent functional group tolerance, and scalability. Moreover, this methodology was also employed as the key step for the total synthesis of desbromoarborescidines A, B, and C. Preliminary mechanistic studies revealed that the palladium catalyst not only formed [Pd-H] to promote the isomerization of α,ß-unsaturated carbonyls but also played a role as a Lewis acid for the final protonation/cyclization.

6.
Org Lett ; 23(23): 9309-9314, 2021 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-34779210

RESUMO

A novel and facile approach to synthesis of 1-substituted cyclopropylamines via phosphine-catalyzed formal tertiary Csp3-H amination of cyclopropanes was described. The indoles, pyrroles, imidazoles, uracils, 2-pyridone, pyrimidin-4(3H)-one, and phthalimide had been proven as good aminating partners. The present protocol features transition-metal-free, excellent regioselectivity, high-atom-economy, and mild reaction conditions and a broad range of substrates. The practicability of this protocol can also be demonstrated with late-stage modification of bioactive molecules, scaled up reaction, and divergent derivatization. Notably, the method has been used in the formal synthesis of the hormone-sensitive lipase (HSL) inhibitor. The mechanistic aspects were elucidated by both experimental and computational studies.

7.
Org Lett ; 23(3): 802-807, 2021 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-33464091

RESUMO

Indole-fused bicyclo[3.2.1]octanes are highly important structural units in natural products and biologically active compounds. However, there has been limited success in the enantioselective synthesis of these skeletons due to the complexity of the structure and the control of the enantioselectivity. Herein an enantioselective construction of indole-fused bicyclo[3.2.1]octanes bearing an all-carbon quaternary bridgehead stereocenter was developed via an aminopalladition-triggered Heck-type reaction. The protocol features mild conditions and good tolerance for a wide range of functional groups. The transformation can also be scaled up to demonstrate its practicability. The mechanistic studies reveal that the formation of an intermediate indol-3-yl palladium species via C-H activation should be ruled out.

8.
Nat Commun ; 9(1): 721, 2018 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-29459667

RESUMO

Saturated 1,4-diazo heterocycles including piperazines, 1,4-diazepanes, and 1,4-diazocanes, are highly important for therapeutic development, but their syntheses are often tedious. We describe here an amphoteric diamination strategy to unite readily available 1,2-, 1,3- or 1,4-diamine derivatives with electron-deficient allenes via a formal [n + 2] (n = 4, 5, 6) cyclization mode to produce the corresponding 1,4-diazo heterocycles in just one step. This strategy features mild reaction conditions, high functional group tolerance, and scalability (gram scale). The reagents used are cheap and readily available and no transition metal catalysts are needed. More sophisticated products containing trifluoromethyl group or bicyclic ring systems can be accessed via a one-pot procedure as well. Our mechanistic studies support that formation of mono-iodinated or chlorinated diamine intermediates is important for the desired transformation and the commonly proposed chloride-iodide exchange process and a radical N-C bond formation is unlikely when the combination of NCS/KI is used.


Assuntos
Alcadienos/química , Diaminas/química , Compostos Heterocíclicos/química , Ciclização , Compostos Heterocíclicos/síntese química , Estrutura Molecular
9.
ACS Catal ; 8(7): 5907-5914, 2018 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34457375

RESUMO

Catalytic ring opening cross coupling reactions of strained cyclopropanols have been useful for the syntheses of various ß-substituted carbonyl products. Among these ring opening cross coupling reactions, the formation of α,ß-unsaturated enone byproducts often competes with the desired cross coupling processes and has been a challenging synthetic problem to be addressed. Herein, we describe our efforts in developing divergent syntheses of a wide range of γ-butyrolactones and δ-ketoesters containing all-carbon quaternary centers via copper-catalyzed cyclopropanol ring opening cross couplings with 2-bromo-2,2-dialkyl esters. Our mechanistic studies reveal that unlike the previously reported cases, the formation of α,ß-unsaturated enone intermediates is actually essential for the γ-butyrolactone synthesis and also contributes to the formation of the δ-ketoester product. The γ-butyrolactone synthesis is proposed to go through an intermolecular radical conjugate addition to the in situ generated α,ß-unsaturated enone followed by an intramolecular radical cyclization to the ester carbonyl double bond. The reactions are effective to build all-carbon quaternary centers and have broad substrate scope.

10.
Sci Signal ; 10(467)2017 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-28223412

RESUMO

Adenylyl cyclase 1 (AC1) belongs to a group of adenylyl cyclases (ACs) that are stimulated by calcium in a calmodulin-dependent manner. Studies with AC1 knockout mice suggest that inhibitors of AC1 may be useful for treating pain and opioid dependence. However, nonselective inhibition of AC isoforms could result in substantial adverse effects. We used chemical library screening to identify a selective AC1 inhibitor with a chromone core structure that may represent a new analgesic agent. After demonstrating that the compound (ST034307) inhibited Ca2+-stimulated adenosine 3',5'-monophosphate (cAMP) accumulation in human embryonic kidney (HEK) cells stably transfected with AC1 (HEK-AC1 cells), we confirmed selectivity for AC1 by testing against all isoforms of membrane-bound ACs. ST034307 also inhibited AC1 activity stimulated by forskolin- and Gαs-coupled receptors in HEK-AC1 cells and showed inhibitory activity in multiple AC1-containing membrane preparations and mouse hippocampal homogenates. ST034307 enhanced µ-opioid receptor (MOR)-mediated inhibition of AC1 in short-term inhibition assays in HEK-AC1 cells stably transfected with MOR; however, the compound blocked heterologous sensitization of AC1 caused by chronic MOR activation in these cells. ST034307 reduced pain responses in a mouse model of inflammatory pain. Our data indicate that ST034307 is a selective small-molecule inhibitor of AC1 and suggest that selective AC1 inhibitors may be useful for managing pain.


Assuntos
Inibidores de Adenilil Ciclases , Adenilil Ciclases/metabolismo , Analgésicos , Sinalização do Cálcio/efeitos dos fármacos , Dor/tratamento farmacológico , Inibidores de Adenilil Ciclases/química , Inibidores de Adenilil Ciclases/farmacologia , Adenilil Ciclases/genética , Analgésicos/química , Analgésicos/farmacologia , Animais , Sinalização do Cálcio/genética , AMP Cíclico/genética , AMP Cíclico/metabolismo , Células HEK293 , Hipocampo/enzimologia , Hipocampo/patologia , Humanos , Camundongos , Dor/enzimologia , Dor/genética , Dor/patologia , Receptores Opioides mu/genética , Receptores Opioides mu/metabolismo
11.
Beilstein J Org Chem ; 12: 702-15, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27340462

RESUMO

Piperazine ranks within the top three most utilized N-heterocyclic moieties in FDA-approved small-molecule pharmaceuticals. Herein we summarize the current synthetic methods available to perform C-H functionalization on piperazines in order to lend structural diversity to this privileged drug scaffold. Multiple approaches such as those involving α-lithiation trapping, transition-metal-catalyzed α-C-H functionalizations, and photoredox catalysis are discussed. We also highlight the difficulties experienced when successful methods for α-C-H functionalization of acyclic amines and saturated mono-nitrogen heterocyclic compounds (such as piperidines and pyrrolidines) were applied to piperazine substrates.

12.
Org Lett ; 17(24): 6074-7, 2015 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-26635251

RESUMO

Novel and general copper-catalyzed cyclopropanol ring opening cross-coupling reactions with difluoroalkyl bromides, perfluoroalkyl iodides, monofluoroalkyl bromides, and 2-bromo-2-alkylesters to synthesize various ß-(fluoro)alkylated ketones are reported. The reactions feature mild conditions and excellent functional group compatibility and can be scaled up to gram scale. Preliminary mechanistic studies suggest the involvement of radical intermediates. The difluoroalkyl-alkyl cross-coupling products can also be readily converted to more valuable and diverse gem-difluoro-containing compounds by taking advantage of the carbonyl group resulting from cyclopropanol ring opening.


Assuntos
Cobre/química , Éteres Cíclicos/química , Hidrocarbonetos Bromados/química , Hidrocarbonetos Fluorados/química , Hidrocarbonetos Fluorados/síntese química , Iodetos/química , Catálise , Estrutura Molecular
13.
Org Lett ; 17(9): 2186-9, 2015 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-25885795

RESUMO

The first copper-catalyzed ring-opening electrophilic trifluoromethylation and trifluoromethylthiolation of cyclopropanols to form Csp3-CF3 and Csp3-SCF3 bonds have been realized. These transformations are efficient for the synthesis of ß-CF3- and ß-SCF3-substituted carbonyl compounds that are otherwise challenging to access. The reaction conditions are mild and tolerate a wide range of functional groups. Application to a concise synthesis of LY2409021, a glucagon receptor antagonist that is used in clinical trials for type 2 diabetes mellitus, is reported as well.


Assuntos
Compostos de Bifenilo/síntese química , Cobre/química , Éteres Cíclicos/química , Hidrocarbonetos Fluorados/síntese química , Iodetos/química , Receptores de Glucagon/antagonistas & inibidores , Alcenos/química , Compostos de Bifenilo/química , Compostos de Bifenilo/farmacologia , Catálise , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hidrocarbonetos Fluorados/química , Hidrocarbonetos Fluorados/farmacologia , Estrutura Molecular , Estereoisomerismo
14.
Org Lett ; 17(9): 2190-3, 2015 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-25885943

RESUMO

A novel copper-catalyzed electrophilic amination of cyclopropanols with O-benzoyl-N,N-dialkylhydroxylamines to synthesize various ß-aminoketones via a sequence that includes C-C bond cleavage and Csp(3)-N bond formation is reported. The reaction conditions are mild and tolerate a wide range of functional groups including benzoate, tosylate, expoxide, and α,ß-unsaturated carbonyls, which are incompatible in the traditional amine nucleophilic conjugate addition and the Mannich reaction conditions. Preliminary mechanistic studies and a proposed catalytic cycle of this umpolung ß-aminoketone synthesis process have been described as well.


Assuntos
Cobre/química , Éteres Cíclicos/química , Cetonas/síntese química , Aminação , Aminas/química , Catálise , Cetonas/química , Estrutura Molecular
15.
Org Lett ; 17(4): 892-5, 2015 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-25668690

RESUMO

Substituted allylic amines and their derivatives are key structural motifs of many drug molecules and natural products. A general, mild, and practical palladium-catalyzed γ-arylation of tertiary allylic amines, one of the most challenging Heck arylation substrates, has been developed. The γ-arylation products were obtained in excellent regio- and stereoselectivity. Moreover, novel and potent adenylyl cyclase inhibitors with the potential for treating neuropathic and inflammatory pain have been identified from the γ-arylation products.


Assuntos
Inibidores de Adenilil Ciclases , Compostos Alílicos/química , Aminas/química , Paládio/química , Catálise , Química Orgânica/métodos , Estrutura Molecular , Estereoisomerismo
16.
Chem Commun (Camb) ; 49(76): 8537-9, 2013 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-23945790

RESUMO

An efficient iridium-catalyzed asymmetric hydrogenation of the fluorinated isoquinoline derivatives has been successfully developed for the synthesis of chiral fluorinated tetrahydroisoquinoline derivatives with up to 93% ee. This methodology features the use of a hydrochloride salt as well as a catalytic amount of halogenated hydantoin which were vital for the reactivity, enantioselectivity, and inhibition of the hydrodefluorination pathway.


Assuntos
Compostos Heterocíclicos/química , Hidrocarbonetos Fluorados/síntese química , Isoquinolinas/química , Catálise , Hidrocarbonetos Fluorados/química , Hidrogenação , Irídio/química , Estrutura Molecular , Estereoisomerismo
17.
Chem Asian J ; 8(7): 1381-5, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23687053

RESUMO

Hi, neighbor! The first organocatalyzed asymmetric transfer hydrogenation of aromatic nitro compounds was successfully developed with up to 99 % ee. The new methodology provides a direct and facile access to enantiopure cyclic nitro compounds with two contiguous stereocenters.

19.
Chem Commun (Camb) ; 49(16): 1660-2, 2013 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-23340596

RESUMO

A novel and efficient method for the generation of o-quinone methide intermediates was developed from the readily available 2-tosylalkylphenols under the mild basic conditions, and their reactions with sulfur ylides were investigated for the stereoselective synthesis of trans-2,3-dihydrobenzofurans.


Assuntos
Benzofuranos/síntese química , Indolquinonas/síntese química , Benzofuranos/química , Indolquinonas/química , Estrutura Molecular , Fenóis/química
20.
Chem Soc Rev ; 42(2): 497-511, 2013 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-23138972

RESUMO

The transition metal catalyzed asymmetric hydrogenation of unsaturated compounds arguably presents one of the most attractive methods for the synthesis of chiral compounds. Over the last few decades, Pd has gradually grown up as a new and popular metal catalyst in homogeneous asymmetric hydrogenation the same as traditional Ru, Rh and Ir catalysts. Much progress has been successfully achieved in the asymmetric reduction of imines, enamines, olefins, ketones and heteroarenes. It was also found that palladium catalyzed asymmetric hydrogenation could be used as a key step in tandem reactions to quickly synthesize chiral compounds. This tutorial review intends to offer an overview of recent progress in homogeneous palladium catalyzed asymmetric hydrogenation and should serve as an inspiration for further advances in this area.


Assuntos
Paládio/química , Alcenos/química , Aminas/química , Catálise , Hidrocarbonetos Aromáticos/química , Hidrogenação , Iminas/química , Cetonas/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...