Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 61
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Org Chem Front ; 11(7): 2008-2014, 2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-39007032

RESUMO

Cyclopropanes are recurrent structural motifs in natural products and bioactive molecules. Recently, biocatalytic cyclopropanations have emerged as a powerful approach to access enantioenriched cyclopropanes, complementing chemocatalytic approaches developed over the last several decades. Here, we report the development of a first biocatalytic strategy for cyclopropanation using ethyl α-diazopyruvate as a novel enzyme-compatible carbene precursor. Using myoglobin variant Mb(H64V,V68G) as the biocatalyst, this method afforded the efficient synthesis of α-cyclopropylpyruvates in high diastereomeric ratios and enantiomeric excess (up to 99% ee). The ketoester moiety in the cyclopropane products can be used to synthesize diverse optically pure cyclopropane derivatives. Furthermore, the enzymatically obtained α-cyclopropylpyruvate products could be converted into enantiopure cyclobutenoates via a metal-free photochemical ring expansion without loss of optical activity.

2.
Angew Chem Int Ed Engl ; 63(30): e202403950, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-38712851

RESUMO

Site-selective ortho/ipso C-H difunctionalizations of aromatic compounds were designed to afford polyfunctionalized arenes including challenging 1,2,3,4-tetrasubstituted ones (62 examples, up to 97 % yields). To ensure the excellent regioselectivity of the process while keeping high efficiency, an original strategy based on a "C-H thianthenation/Catellani-type reaction" sequence was developed starting from simple arenes. Non-prefunctionalized arenes were first regioselectively converted into the corresponding thianthrenium salts. Then, a palladium-catalyzed, norbornene (NBE)-mediated process allowed the synthesis of ipso-olefinated/ortho-alkylated polyfunctionalized arenes using a thianthrene as a leaving group (revisited Catellani reaction). Pleasingly, using a commercially available norbornene (NBE) and a unique catalytic system, synthetic challenges known for the Catellani reaction with aryl iodides were smoothly and successfully tackled with the "thianthrenium" approach. The protocol was robust (gram-scale reaction) and was widely applied to the two-fold functionalization of various arenes including bio-active compounds. Moreover, a panel of olefins and alkyl halides as coupling partners was suitable. Pleasingly, the "thianthrenium" strategy was successfully further applied to the incorporation of other groups at the ipso (CN/alkyl/H, aryl) and ortho (alkyl, aryl, amine, thiol) positions, showcasing the generality of the process.

3.
Chem Commun (Camb) ; 60(16): 2244-2247, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38317563

RESUMO

Selective one-pot sequential ortho-/meta-C-H functionalizations provided highly desirable polyfunctionalized arenes. Starting from readily available carboxylic acid derivatives, the concomitant formation of C-O and C-halogen bonds was achieved under mild reaction conditions (12 examples, up to 75% yield). The utility of the products was illustrated with post-functionalization reactions and Metiglinid synthesis.

4.
Chemistry ; 30(8): e202303070, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-37985211

RESUMO

The catalytic asymmetric synthesis of highly functionalized cyclopropanes from 2-substituted allylic derivatives is reported. Using ethyl diazo acetate, the reaction, catalyzed by a chiral ruthenium complex (Ru(II)-Pheox), furnished the corresponding easily separable cis and trans cyclopropanes in moderate to high yields (32-97 %) and excellent ee (86-99 %). This approach significantly extends the portfolio of accessible enantioenriched cyclopropanes from an underexplored class of olefins. DFT calculations suggest that an outer-sphere mechanism is operative in this system.

5.
Chem Commun (Camb) ; 60(2): 196-199, 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38047933

RESUMO

A divergent photoinduced selective synthesis of thiocyanate and isothiocyanate derivatives from readily available carboxylic acids was developed using N-thiocyanatosaccharin and a catalytic amount of base or acid. This molecular editing strategy allowed the functionalization of bioactive compounds. A mechanism for the transformation was proposed based on control experiments.

6.
Org Lett ; 25(26): 4928-4933, 2023 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-37353228

RESUMO

We report a rhodium-catalyzed anti-Markovnikov regioselective hydrosilylation of trifluoromethylalkenes with substituted silanes giving various α-trifluoromethyl-ß-silanes in good to excellent yields. The hydrogenation products were obtained via the same key intermediate treated with methanol as a protic solvent. Both transformations had a broad functional tolerance and were expected to facilitate the construction of complex α-trifluoromethyl compounds.

7.
Chem Rec ; 23(11): e202300172, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37358334

RESUMO

Due to their high versatility borylated and silylated compounds are inevitable synthons for organic chemists. To escape the classical hydroboration/hydrosilylation paradigm, chemists turned their attention to more modern and green methods such as photoredox chemistry and electrosynthesis. This account focuses on novel methods for the generation of boryl and silyl radicals to forge C-B and C-Si bonds from our group.

8.
Chemistry ; 29(43): e202301417, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37194748

RESUMO

Herein, we developed a photoinduced Minisci reaction on a large panel of diazines with good to excellent yields (28 examples, 44 % to 89 %). The reaction using 4CzIPN (1 mol %) as photoinitiator was carried out under white LED irradiation and required a slight excess of the acid reagent (1.2 equiv.). Cyclization reactions were then developed to access original N-heterocycles building blocks for drug discovery programs. An extension of the reaction to continuous flow was also reported. Finally, the mechanism of the transformation was studied suggesting a plausible radical chain mechanism.

9.
Org Lett ; 24(45): 8343-8347, 2022 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-36350256

RESUMO

gem-Bromofluoroalkenes have been combined with phosphite under irradiation, in the presence of Fukuzumi's catalyst (9-mesityl-10-methylacridinium perchlorate) as an organic photocatalyst, to provide valuable gem-fluorophosphonate derivatives, known as stable mimics of phosphates. The desired products were obtained in good to excellent yields, and the reaction showed very good chemical tolerance.


Assuntos
Alcenos , Estrutura Molecular , Catálise
10.
Chemistry ; 28(71): e202202286, 2022 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-36200571

RESUMO

We describe herein the first halogen dance (HD) in continuous flow on 2-chloro-3-bromopyridine by selectively trapping a (pyridin-4-yl)lithium species that is known to undergo the halogen-dance process. In addition, this lithiated intermediate was trapped at lower temperature before the HD occurs. The HD process was extended to fluoro-iodopyridines by using various electrophiles to afford 28 examples with yields ranging from 42 to 97 % with very short residence times. Finally, scale up of the reaction was demonstrated, affording a promising space-time yield (STY) of 4.2 kg.h-1 .L-1 .


Assuntos
Dança , Halogênios , Lítio , Temperatura
11.
Chemistry ; 28(66): e202202194, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36067044

RESUMO

The electrochemical synthesis of fluorinated allyl silanes and boronates was disclosed. The addition of electrogenerated boryl or silyl radicals onto many α-trifluoromethyl or α-difluoromethylstyrenes in an undivided cell allowed the formation of a large panel of synthetically useful gem-difluoro and γ-fluoroallyl boronates and silanes (64 examples, from 31 % to 95 % yield). In addition, a scale up of the reactions under continuous flow was showcased using an electrochemical reactor with promising volumetric productivity (688 g.L-1 .h-1 and 496 g.L-1 .h-1 ). Moreover, the synthetic utility of these building blocks was highlighted through versatile transformations. Finally, plausible reaction mechanisms were suggested to explain the formation of the products.


Assuntos
Silanos
12.
Chemistry ; 28(52): e202201514, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-35652371

RESUMO

Herein, we disclosed the contra-thermodynamic E→Z isomerization of alkenyl silanes, according to the in situ formation of a chromophoric species, in the presence of rac-BINAP as the catalyst. The reaction carried out in DMSO or CH3 CN under irradiation at 405 nm allowed the interconversion of the E-isomers into the Z-congeners in good to excellent yields and outstanding Z/E selectivities, on 18 examples. Finally, the mechanism of this E→Z isomerization was studied to get insight into the reaction mechanism.

13.
Chemistry ; 28(55): e202201928, 2022 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-35736795

RESUMO

In this study, a practical and straightforward synthesis of ß-(E)-trifluoromethylstyrenes by ruthenium-catalyzed C-H bond activation was developed. The readily available and inexpensive 2-bromo-3,3,3-trifluoropropene (BTP), a non-ozone depleting reagent, was used as a reservoir of 3,3,3-trifluoropropyne. With this approach, the monofunctionalization of a panel of heteroarenes was possible in a safe and scalable manner (23 examples, up to 87 % yield). Mechanistic investigations and density functional theory (DFT) calculations were also conducted to get a better understanding of the mechanism of this transformation. These studies suggested that 1) a cyclometallated ruthenium complex enabled the transformation, 2) this complex exhibited high efficiency in this transformation compared to the commercially available [RuCl2 (p-cymene)]2 and 3) the mechanism proceeded through a bis-cyclometallated ruthenium intermediate for the carboruthenation step.

14.
J Org Chem ; 87(14): 9210-9221, 2022 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-35749447

RESUMO

α-Fluorinated acrylates could act as Michael acceptors and become a platform toward the synthesis of relevant complex molecules. Very few conjugate additions have been developed in the literature with these specific substrates, and herein, we reported the first phospha-Michael addition (PMA) on α-trifluoromethylacrylates and α-fluoromethylacrylates. The reaction proved to be highly tolerant and gave original products containing contiguous C-P and C-CFY2 (Y = F or H) bonds in good to excellent yields and diastereoselectivities.


Assuntos
Acrilatos , Estereoisomerismo
15.
Chemistry ; 28(42): e202201254, 2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-35522085

RESUMO

The catalytic asymmetric synthesis of highly functionalized cyclopropanes from α-substituted allyl sulfones and silanes is reported. The reaction, using α-aryl diazoacetates or diacceptor diazo reagents, catalyzed by a chiral rhodium complex (Rh2 ((S)-BTPCP)4 ), furnished the corresponding cyclopropanes in moderate to high yields (27-97 %), high diastereoselectivities (68 : 32 to 20 : 1 d.r.) and moderate to excellent ee (40-99 %). This methodology offers a privileged access to an underexplored class of enantioenriched cyclopropanes with a high level of functionality, an asset for further post-functionalization and their incorporation into more complex structure.

16.
Chemistry ; 28(47): e202201438, 2022 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-35593399

RESUMO

The first diastereo- and enantioselective cyclopropanation reactions of electron-deficient allenes with donor-acceptor and diacceptor diazo reagents are described. The desired enantioenriched alkylidenecyclopropanes (ACPs) were obtained in high yields with high diastereo- and enantioselectivities in the presence of Rh2 ((S)-TCPTAD)4 or Rh2 ((R)-BTPCP)4 catalysts (up to 95 % yield, >95 : 5 d.r. and 99 : 1 e.r.). This methodology gave a direct access to ACPs bearing multiple electron-deficient substituents and allows to further expand the availability of ACPs chemistry. Interestingly, during the examination of the scope of this reaction, the asymmetric intramolecular C-H insertion reaction into tert-butyl group was observed as a side reaction with up to 94 : 6 e.r.

17.
ACS Omega ; 7(6): 4868-4878, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-35187307

RESUMO

Over the years, numerous modifications to the structure of proline have been made in order to tune its effects on bioactive compounds. Notably, the introduction of a cyclopropane ring or a fluorine atom has produced interesting results. Herein, we describe the synthesis of a proline containing fluorocyclopropane. This modified amino acid was inserted into a tripeptide, whose conformation was studied by nuclear magnetic resonance and density functional theory calculations.

18.
J Flow Chem ; 12(2): 147-151, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34631154

RESUMO

We describe the total flow synthesis of the widely prescribed anti-inflammatory COX-2 inhibitor Celecoxib from 2-bromo-3,3,3-trifluoropropene, as a convenient and available trifluoromethyl building block, to generate trifluoropropynyl lithium and to trap it immediately with an aldehyde. Oxidation of the obtained alcohol into ketone followed by condensation with 4-sulfamidophenylhydrazine afforded the targeted drug with full regioselectivity. It is noteworthy that the quality of these flow reactions (50% overall yield within 1 h cumulated residence time over 3 steps) directly furnished the target API and intermediates with excellent purity. Supplementary Information: The online version contains supplementary material available at 10.1007/s41981-021-00205-x.

19.
ACS Org Inorg Au ; 2(2): 148-152, 2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-36855456

RESUMO

Herein, the electrochemical hydrosilylation of alkynes is reported. In the presence of the Suginome reagent (PhMe2Si-Bpin), a large panel of terminal alkynes and internal alkynes was successfully converted into the hydrosilylated product in good to excellent yields and good selectivity in favor of the linear product. Preliminary mechanistic study supported the involvement of a silyl radical, which reacted on the alkyne.

20.
Molecules ; 26(23)2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34885756

RESUMO

Herein, we report a continuous flow process for the synthesis of 2,6-diisopropylphenol-also known as Propofol-a short-acting intravenous anesthesia, widely used in intensive care medicine to provide sedation and hypnosis. The synthesis is based on a two-step procedure: a double Friedel-Crafts alkylation followed by a decarboxylation step, both under continuous flow.


Assuntos
Hipnose Anestésica , Propofol/síntese química , Anestesia Intravenosa , Humanos , Propofol/química , Propofol/uso terapêutico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...