RESUMO
Herein, a transition-metal-free phosphorylation of benzyl fluorides with P(O)-H compounds is disclosed. In the presence of tBuOK, various benzyl fluorides react with P(O)-H compounds to produce the corresponding benzyl phosphine oxides, phosphinates, and phosphonates in good to high yields. This base-promoted phosphorylation reaction offers a facile and general strategy for the construction of a C(sp3)-P bond.
RESUMO
Herein, visible light-induced, nickel-catalyzed direct functionalization of the Hantzsch esters (HEs) with readily accessible alkyl bromides has been successfully achieved by taking advantage of HE as the reductant and substrate through an aromatization-dearomatization process. In this strategy, the single electron reduction of alkyl bromides by reactive Ni(I) species is essential for the success of this late-stage transformation. A wide range of 4-alkyl-1,4-dihydropyridines were rapidly assembled in moderate to good yields under mild conditions, rendering this photoinduced approach attractive for synthetic and medicinal chemistry.
RESUMO
Nickel/photoredox catalysis has emerged as a powerful platform for exploring nontraditional and challenging cross-couplings. Herein, a metallaphotoredox catalytic protocol has been developed on the basis of a tertiary amine-ligated boryl radical-induced halogen atom transfer process under blue-light irradiation. A wide variety of aryl and heteroaryl bromides featuring different functional groups and pharmaceutical moieties were facilely coupled to rapidly install C(sp3)-enriched aromatic scaffolds. The compatibility of Lewis base-ligated borane with nickel catalysis was well exemplified to extend the chemical space for Ni-catalyzed cross-electrophile coupling.
RESUMO
A visible-light-induced defluorinative dichloromethylation of α-CF3 alkenes was developed with cheap and readily accessible chloroform simultaneously as a dichloromethylation reagent and reaction medium, leading to the facile preparation of new polyhalogenated scaffolds. Notably, the change from CHCl3 to CDCl3 offers a straightforward pathway for accessing the deuterated analogues with excellent degrees of D incorporation. Mechanistic studies suggested the reaction underwent a radical addition of the dichloromethyl radical with alkenes, followed by sequential single-electron transfer and defluorination. This protocol features mild conditions, easy operation, facile scalability, and high efficiency, allowing convenient access to dichloronated gem-difluoroalkenes.
RESUMO
Reported herein is a visible-light-induced, catalyst-free intramolecular cyclization of 4-phenylsulfonyl-2,3,5,6-tetrachloropyridine, leading to rapid assembly of a series of unprecedented benzo[4,5]thieno[3,2-c]pyridine 5,5-dioxide scaffolds under mild conditions. The rational introduction of a perchloropyridin-4-yl module significantly facilitated this photoinduced process and offers a versatile platform for broad structural variation. Mechanistic studies revealed that a newly identified charge-transfer complex with carbonate is crucial to this photoinduced process.
RESUMO
Reported herein is a photoredox-catalyzed amination of o-hydroxyarylenaminones with tert-butyl ((perfluoropyridin-4-yl)oxy)carbamate, a versatile amidyl-radical precursor developed in our laboratory. This work establishes a new cascade pathway for the assembly of a range of 3-aminochromones under mild conditions. Downstream transformations of the obtained 3-aminochromones to construct diverse amino pyrimidines greatly broaden the applications of this photocatalyzed protocol.
Assuntos
Cromonas , Aminação , CatáliseRESUMO
A phosphine-mediated, well-designed Morita-Baylis-Hillman-type/Wittig cascade for the rapid assembly of a quinolinone framework from benzaldehyde derivatives is developed for the first time. By rationally combining I2/NIS-mediated cyclization, biologically relevant 3-(benzopyrrole/furan-2-yl) quinolinones were facilely synthesized in a one-pot process by starting from 3-styryl-quinolinones bearing an o-hydroxy/amino group, significantly expanding the chemical space of this privileged skeleton. Further utility of this protocol is illustrated by successfully performing this transformation in a catalytic manner through in situ reduction of phosphine oxide by phenylsilane.
Assuntos
Fosfinas , Quinolonas , Ciclização , FuranosRESUMO
The mechanism of the phosphine-catalysed domino sequence of alkynoates and activated methylenes has been computationally studied. The computational results revealed that the [3 + 2] annulation sequence could be ruled out, due to a difficult Knoevenagel condensation of aromatic aldehydes and active methylenes. The reaction proceeds through a [4 + 1] annulation pathway, which involves a phosphine-catalysed MBH-type reaction followed by a [1,5]-proton shift and dehydration to afford vinyl phosphonium intermediates as four-carbon synthons in the annulation reaction. Then 1,3-dicarbonyls act as nucleophiles to attack vinyl phosphonium intermediates, subsequently leading to a stepwise [1,3]-proton shift and an intramolecular nucleophilic attack to close the five-member ring.
RESUMO
A metal-free photosensitized protocol for regioselective diamination of alkene feedstocks over a single step was developed based on the rationally designed bifunctional diamination reagent, thus affording a range of differentially protected 1,2-diamines in moderate to high yields. Mechanistic studies reveal that the reaction is initiated with a triplet-triplet energy transfer between thioxanthone catalyst and diamination reagent, followed by fragmentation to simultaneously generate long-lived iminyl radical and transient amidyl radical. The excellent regioselectivity presumably stems from the large reactivity difference between two different N-centered radical species. This protocol is characterized by excellent regioselectivity, broad functional group tolerance, and mild reaction conditions, which would enrich the diversity and versatility of facilitate the diversity-oriented synthesis of 1,2-diamine-containing complex molecule scaffolds.
RESUMO
An unprecedented photoredox-catalyzed phosphine-mediated deoxygenation of hexafluoroacetone hydrate was established to accomplish the hydroxylpolyfluoroalkylation of electron-deficient alkenes. A range of bis(trifluoromethyl)carbinols were facilely accessed by using readily available hexafluoroacetone hydrate, instead of toxic gaseous hexafluoroacetone. A range of electron-deficient alkenes are tolerated, giving the corresponding hydro-hydroxylpolyfluoroalkylated products in moderate to high yields. Remarkable features of this synthetic strategy include operational simplicity, mild reaction conditions, excellent regioselectivity, and broad functional group tolerance. The success of this strategy relies on the delicate utilization of aldehyde/ketone-gem-diol intrinsic equilibrium, which offers an innovated open-shell pathway for the assembly of synthetically challenging polyfluoroalkylated scaffolds.
Assuntos
Alcenos , Fluorocarbonos , Catálise , AcetonaRESUMO
Aiming at the valuable methylation process, readily available and inexpensive N,N,N',N'-tetramethylethylenediamine (TMEDA) was first identified as a new methyl source in photoredox-catalyzed transformation in this work. By virtue of this simple methylating reagent, a facile and practical protocol for the direct C-H methylation of N-heteroarenes was developed, featuring mild reaction conditions, broad substrate scope, and scalability. Mechanistic studies disclosed that a sequential photoredox, base-assisted proton shift, fragmentation, and tautomerization process was essentially involved.
Assuntos
Etilenodiaminas , Prótons , Catálise , MetilaçãoRESUMO
A visible light-promoted radical relay of N-allylbromodifluoroacetamide with quinoxalin-2(1H)-ones was developed in which 5-exo-trig cyclization and C-C bond formation were involved. This protocol was performed under mild conditions to facilely offer a variety of hybrid molecules bearing both quinoxalin-2(1H)-one and 3,3-difluoro-γ-lactam motifs. These prepared novel skeletons would expand the accessible chemical space for structurally complex heterocycles with potential biological activities.
Assuntos
Luz , Quinoxalinas , Ciclização , Lactamas , Estrutura MolecularRESUMO
A visible-light-driven, photocatalyst-free route starting from easily accessed ortho-hydroxycinnamic esters and O-perfluoropyridin-4-yl oximes has been successfully developed to rapidly assemble a wide range of 3-cyanoalkyl coumarins. This process does not require addition of external photocatalysts, exhibiting beneficial features including mild reaction conditions, synthetic simplicity, and excellent substrate compatibility. Extensive mechanistic investigations revealed that the in situ generated phenolate anions served as photosensitizers to drive this photoinduced transformation.
RESUMO
A library of new 2-substituted pyrrolo[1,2-b]pyridazine derivatives were rapidly assembled and identified as PARP inhibitors. Structure-activity relationship for this class of inhibitor resulted in the discovery of most potent compounds 15a and 15b that exhibited about 29- and 5- fold selective activity against PARP-1 over PARP-2 respectively. The antiproliferative activity of the as-prepared compounds were demonstrated by further celluar assay in BRCA2-deficient V-C8 and BRCA1-deficient MDA-MB-436 cell lines, displaying that compound 15b could robustly reduce the corresponding cell proliferation and growth with CC50s of 340 and 106 nM respectively. The PK property of 15b was also investigated here.
Assuntos
Antineoplásicos/farmacologia , Poli(ADP-Ribose) Polimerase-1/antagonistas & inibidores , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Piridazinas/farmacologia , Pirróis/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Poli(ADP-Ribose) Polimerase-1/metabolismo , Inibidores de Poli(ADP-Ribose) Polimerases/síntese química , Inibidores de Poli(ADP-Ribose) Polimerases/química , Piridazinas/síntese química , Piridazinas/química , Pirróis/síntese química , Pirróis/química , Relação Estrutura-AtividadeRESUMO
Nitro compounds are a predominant class of synthetic intermediates and building blocks for the preparation of a wide range of nitrogen-containing compounds in the chemical industry. As such, impressive progress has been currently made in the nitration of aromatics and olefins with excellent functional group tolerance and site-selectivity. In this mini review, we intend to highlight the regiospecific nitration of arenes and alkenes in various reaction systems. The involved mechanisms are discussed as well.
RESUMO
A novel phosphine-catalysed, one-pot domino approach for the annulation of 2-formylphenyl alkynoates with activated methylene compounds to construct various cyclopentene-fused dihydrocoumarins is reported. This developed strategy provides a facile and efficient approach for the synthesis of structurally complex coumarins from inexpensive and readily available alkynoates.
RESUMO
O-Perfluoropyridin-4-yl group was first installed onto cycloketone oximes as a new electrophore, which was proven to be efficient iminyl radical precursors under photocatalytic and thermal conditions. A range of O-perfluoropyridin-4-yl oximes were successfully utilized in C(sp2)-C(sp3) bond formations of quinoxalin-2(1H)-ones and alkenes, providing facile accesses to a range of functionalized alkylnitriles.
RESUMO
Acyl oximes are directly used as the acyl radical precursors in the hydroacylation reactions for the first time. In this work, acyl radicals can be effectively generated via ß-scission of a phosphoranyl radical under photocatalytic conditions. As a result, the hydroacylation of alkenes triggered by the resulting acyl radicals leads to facile syntheses of a range of valuable ketones.
RESUMO
A visible-light-induced, catalyst-free radical cross-coupling cyclization of diselenides or disulfides with N-allylbromodifluoroacetamide has been developed. This developed protocol exhibits good functional group tolerance and affords a variety of 4-thio- and 4-seleno-substituted 3,3-difluoro-γ-lactams in moderate to good yields. Based on control experiments, a plausible radical-radical cross-coupling pathway is proposed.
RESUMO
A series of 6-aminocarbonyl pyrrolo[2,1-f][1,2,4]triazine derivatives were designed by scaffold hopping strategy. The IC50 values of compound 14a against PI3Ks were measured, showing selective activity against p110α and p110δ with IC50s of 122 nM and 119 nM respectively. All the synthesized compounds were evaluated for their antiproliferative activity against human cancer cells by SRB assay. Compounds 14a, 14p and 14q exhibited potent antiproliferative activity against five types of human cancer cells and the PK property of 14q was also investigated here.