RESUMEN
Reaching the formidable C-H corners has been one of the top priorities of organic chemists in the recent past. This prompted us to disclose herein a vicinal annulation of 2-iodo benzoates, indoles, and carbazoles with N-embedded 1,6-enynes through 7-/8-membered palladacycles. The relay does not require the assistance of any directing group, leading to multicyclic scaffolds, which are readily diversified to an array of adducts (with new functional tethers and/or three contiguous stereocenters), in which we showcase a rare benzylic mono-oxygenation.
RESUMEN
Electrophilic cyclization and concomitant C-H annulation constitute an expedient cascade strategy for the construction of multicyclic scaffolds with precise substitutional patterns. We report here a novel Pd-catalyzed cyclative annulation of ynone oxime with activated alkynes. The cascade features a dual regioselectivity including site selective C-H activation and chelation-assisted selective insertion of alkynes. Control experiments together with kinetic experiments give insights into the mechanism.
RESUMEN
Herein, we have disclosed a rare example of an intramolecular doubly vinylogous Michael addition (DVMA). The reaction design exploits the innate reactivity of ortho-heteroatom substituted para-quinone methide (p-QM) derivatives. The sequential reaction of p-QMs and activated allyl halides proceeds through heteroatom-allylation, DVMA and oxidation to furnish a diverse range of 2-alkenyl benzofuran and 2-alkenyl indole derivatives in high yields.
RESUMEN
A facile one-pot synthesis of five- and six-membered fused dihydropyridines such as chromenodihydropyridines, pyrazolodihydropyridines and isoxazolopyridines was accomplished for the first time by employing PPh3-NBS via a formal [3 + 2 + 1] cycloaddition of 1,3-bisnucleophiles (i.e., 2-aminochromone, 4-aminochromone, 5-aminopyrazole and 5-aminoisoxazole), ß-enaminones and aldehydes in aqueous medium. The present approach involves a Michael type addition followed by intramolecular cyclization leading to the formation of two new C-C bonds and one C-N bond. High compatibility and excellent yields are the advantages of this protocol.
RESUMEN
We present here a rhodium-catalyzed oxidative three-point double annulation of enaminones with propargylic alcohols via a C-H and a C-N bond activation to access arylnaphthalene-based lignan derivatives. The key step in the reaction is the regioselective insertion of propargylic alcohol into the rhoda-cycle, a result of hydroxyl rhodium coordination. Necessary control experiments and KIE studies were conducted to determine the mechanism.
Asunto(s)
Lignanos , Rodio , Catálisis , Oxidación-ReducciónRESUMEN
A synthetic strategy that efficiently constructs complex molecular diversity in a few steps will always be embraced by organic chemists. Here, we report a cascade reaction of enynones with enaminones via carbene insertion and aryl migration to engineer distinctive multisubstituted furans with an all-carbon quaternary center, and could extend the protocol in the same pot towards furano-pyrrole bis-heterocycles. Heterogeneity of this protocol was proved with the upshot of divergent chemical space under a relatively mild reaction environment.
Asunto(s)
Furanos , Pirroles , Catálisis , Ciclización , Furanos/química , Estructura Molecular , Pirroles/químicaRESUMEN
Herein, we present a metal-free visible-light-induced eosin-y-catalyzed deaminative strategy for the sequential alkylation/cyclization of N-methacryloyl-2-phenylbenzoimidazoles with alkyl amine-derived Katritzky salts, which provides an efficient avenue for the construction of various benzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one derivatives in moderate to excellent yields under mild reaction conditions. The key enabling feature of this novel reaction includes utilization of redox-active pyridinium salts from abundant and inexpensive primary amine feedstocks that were converted into alkyl radicals via C-N bond scission and subsequent alkylation/cyclization with N-methacryloyl-2-phenylbenzoimidazoles by the formation of two new C-C bonds. In addition, we implemented this protocol for a variety of amino acids, affording the products in moderate yields. Moreover, the novel, environmentally benign batch protocol was further carried out in a continuous-flow regime by utilizing a perfluoroalkoxy alkane tubing microreactor under optimized reaction conditions with a blue light-emitting diode light source, enabling excellent yields and a shorter reaction time (19 min) versus the long reaction time (16 h) of the batch reaction. The reaction displays excellent functional group tolerance, easy operation, scalability, mild reaction conditions, and broad synthetic utility.
RESUMEN
In the realm of transition-metal catalyzed arene functionalization, rhodium(III) catalysis is considered as exemplary due to its propensity to activate C-H bonds to obtain comprehensive molecular assembly. Herein, we demonstrate a new rhodium(III) catalyzed assembly of polyheterocyclic scaffolds via C-H activation and regioselective annulation of 4-arylbut-3-yn-1-amines with 4-hydroxy-2-alkynoates. Heterocyclization and trans-metalation prior to annulation is the key for initiation of this relay redox-neutral catalytic cascade.
RESUMEN
Herein, we present a copper-catalyzed tandem reaction of 2-aminoimidazolines and ortho-halo(hetero)aryl carboxylic acids that causes the regioselective formation of angularly fused tricyclic 1,2-dihydroimidazo[1,2-a]quinazolin-5(4H)-one derivatives. The reaction involved in the construction of the core six-membered pyrimidone moiety proceeded via regioselective N-arylation-condensation. The presented protocol been successfully applied to accomplish the total synthesis of TIC10/ONC201, which is an active angular isomer acting as a tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL): a sought after anticancer clinical agent.
Asunto(s)
CobreRESUMEN
A copper-catalyzed tandem process integrating regioselective N-arylation, followed by aza-Michael addition, is disclosed using 2-aminobenzothiazoles and ortho-halo cinnamic acid congeners. This process generated diverse tetracyclic 5H-benzothiazolo[3,2-a]quinazoline derivatives in moderate to good yields. The present tandem reaction appears to proceed through concomitant ring opening of 2-aminobenzothiazole and S-arylation to give the ortho-cyanamide-substituted diaryl thioether intermediate. The thus generated intermediate likely undergoes an unprecedented Truce-Smiles-type rearrangement involving S- to N-aryl migration, followed by reformation of the thiazole ring and intramolecular aza-Michael addition to furnish the title products.
RESUMEN
A regio- and stereoselective synthesis of unsymmetrically substituted pentafulvenes is reported via the condensation of readily available ynones and amino crotonates under very mild conditions. The mechanism of this 3 + 2 annulation involved a vinylogous Michael addition followed by an intramolecular enamine aldol condensation. Substrates with o-bromo tether further cyclized to pentannulated hydroquinolines through an isomerization/SNAr in the same reaction pot at the elevated temperature.
RESUMEN
A series of bis(4'-tert-butylbiphenyl-4-yl)aniline (BBA) functionalized borondipyrromethene (BODIPY) dyads, Dyads 1-3, containing the BBA group tethered to BODIPY moiety either directly or through a phenyl or alkynyl phenyl spacers are synthesized, and the light-mediated charge transfer within the chromophores has been systematically investigated. The crystal structure of Dyad-1 showed a tilt of 44.2° between the BODIPY and BBA molecular planes and intermolecular C-H···π interactions with these moieties. Cyclic voltammetric and computational studies showed that the BBA moiety can act as the electron donor (D) and BODIPY as the electron acceptor (A) and the optical absorption studies revealed that an increase in the conjugation of the linker from Dyad-1 to Dyad-2 resulted in bathochromic shifts. Steady-state fluorescence studies involving photoexcitation of the BBA moiety at 326 nm resulted in the decrease in fluorescence intensity of the BBA, indicating the possibility of sequential occurrence of faster photoinduced energy transfer (PEnT) followed by the photoinduced electron transfer (PET) or solely PET within the dyads, and the driving forces of the charge separation were calculated to be exothermic in all of the employed solvents. Parallel time-resolved fluorescence experiments involving the excitation of BBA moiety also supported the occurrence of charge separation in these dyads. Interestingly, excitation of the BODIPY moiety of Dyad-1 and Dyad-2 at 490 nm in solvents of increasing polarity leads to a red-shifted BODIPY emission with weakened intensity. This spectral behavior indicated the occurrence of emission from the locally excited (LE) state in nonpolar solvents, whereas formation of an LE state followed by the rotation of the chromophores at the D-A bond leads to a low energy twisted intramolecular charge transfer state (TICT), resulting in a charge-separated state BBA+â¢-BODIPY-⢠in polar solvents. Furthermore, the hydrophobicity studies involving the solutions of dyads in admixtures of polar tetrahydrofuran (THF) and nonpolar hexanes revealed that when the fraction of hexanes in these mixtures is increased, the emission of BODIPY moiety was observed to be blue-shifted and exhibited enhanced intensity supporting the occurrence of TICT in these dyads.
RESUMEN
BF3·Et2O-mediated synthesis of multisubstituted indenes from alkyl aryl-1,3-dienes and aromatic aldehydes through tandem addition/4π-electrocyclization/benzylation via tetrahydroindeno-oxepine/quinone methide followed by an intramolecular 1,6-hydride transfer is described. This novel reaction pathway is established by the isolation of potential intermediates and with the support of deuterium-labeling studies. In addition, the generality of this method is demonstrated by reacting various aromatic aldehydes, which ascertains the role of the electronic effect of aldehydes in the formation of indene derivatives and tetrahydroindeno-oxepines.
RESUMEN
Aza-enediynes underwent a facile, regioselective gold-catalysed cascade cycloisomerisation to furnish dihydrobenzo[f]isoquinoline derivatives in excellent yields. The aza-enediynes were conveniently prepared via a formal vinylic displacement reaction of allyl bromosulfones. The latter functioned as a stable and easily accessible synthetic equivalent of allenyl sulfone.
RESUMEN
The rhodium-catalyzed arylative cyclization of enone tethered-cyclohexadienones has been developed with high efficiency, thus providing cis-fused bicyclic enones in good yields and with excellent diastereoselectivities. Furthermore, this mild transformation has a broad range of substrate scope and excellent functional group tolerance. In addition, bicyclic products have an enone functionality, which can be a synthetically valuable handle for further transformations.
RESUMEN
Green chemistry comprises a new approach in the synthesis of biologically active compounds using biocatalysts, thus diminishing the hazards for human health and environmental pollution. Asymmetric bioreduction is one of the most widely employed strategies in chemoenzymatic synthesis to produce enantiomerically pure chiral alcohols. The present study highlights the use biocatalyst Daucus carota for selective bioreduction of quinoxaline ketones 1a-6a to their corresponding optically pure alcohols 1b-6b in high yields (up to 84%) and good enantioselectivity (up to 98%). The absolute configuration of the chiral product (R)-1-(3-methyl 7-nitroquinoxalin-2-yl) ethan-1-ol 2b was confirmed by X-ray crystallography studies. The chiral R-configuration of the products obtained was confirmed by absolute configuration studies and was assigned following anti-Prelogs rule. Quinoxaline pharmacophores form a part of well-known potent drug molecules; hence, the chiral products were studied for determination of their molecular properties using SwissADME property analyser. All the chiral products show no Lipinski rule violations and are expected to have good oral bioavailability. As per the molecular properties prediction studies, the compound 6b (R)-1-(6,7-dichloro-3- methylquinoxalin-2-yl) ethanol is observed to show the best physicochemical properties to be a good lead molecule. Thus, the sustainable methodology was developed, and it confirms the synthesis of novel quinoxaline chiral alcohols in a simple, inexpensive, and eco-friendly condition using D carota.
RESUMEN
A copper-catalyzed one-pot multicomponent protocol has been developed for construction of spiro heterocycles. The domino approach leads to the synthesis of spiro oxazolidinones starting from ketones, arylacetylenes, and isocyanates via catalytic addition, hydroamination, and cyclization involving consecutive C-C, C-O, and C-N bond formations.
RESUMEN
An iodine promoted tandem oxidative condensation of benzylamines and 2-methylquinazolin-4-(3H)-ones was developed to yield imidazo[1,5-a]quinazolin-5(4H)-ones via dual C(sp3)-H amination under metal free conditions in a greener way using molecular oxygen as a terminal oxidant. This tandem transformation provides an efficient approach to construct various functionalized imidazo[1,5-a]quinazolin-5(4H)-ones in a straightforward manner via a sequential amination-oxidation-annulation-aromatisation.
RESUMEN
Intermolecular tandem copper-catalyzed O-arylation-oxidative acylation (cross dehydrogenative coupling-CDC) has been developed under air as an oxidant. The reaction between 2,4-dihydro-3H-pyrazol-3-ones and ortho-halo aryl carboxaldehydes furnished the corresponding chromone fused pyrazoles, in a straightforward manner. The synthetic utility of the presented tandem catalysis has been demonstrated with the synthesis of an A2-subtype selective adenosine receptor antagonist in only two steps.
RESUMEN
A new series of 1-((9-chloro-2,3-dimethyl-6,7-dihydro-5H-benzo[7]annulen-8-yl)methoxy)-3-(4-phenylpiperzin-1-yl) propan-2-ols (6a-k) have been designed, synthesized and their structures were established by spectroscopic data (FT-IR, 1H NMR, 13C NMR, HRMS) and further confirmed by X-ray analysis. The newly synthesized compounds 6a-k were evaluated for their in vitro anti-proliferative activity against four cancer cell lines such as HeLa (cervical), MDA-MB-231 (breast), A549 (lung) and MIAPACA (pancreatic). Among the compounds tested, the compound 6e displayed most potent activity against four cancer cell lines with GI50 values ranging from 0.010 to 0.097µM. The structure and anti-proliferative activity relationship was further supported by in silico molecular docking study of the active compounds against Colchicine binding site of ß-tubulin.