Showing papers on "Enone published in 2018"
TL;DR: An unprecedented ligand-controlled regiodivergent Cu(I)-catalyzed asymmetric intermolecular (3 + 2) cycloaddition reaction of α-substituted iminoesters with β-fluoromethyl β,β-disubstituting enones was developed, opening up a new era for medicinal chemistry and diversity-oriented synthesis.
Abstract: An unprecedented ligand-controlled regiodivergent Cu(I)-catalyzed asymmetric intermolecular (3 + 2) cycloaddition reaction of α-substituted iminoesters with β-fluoromethyl β,β-disubstituted enones was developed. This novel strategy provides an efficient method for the enantioselective regiodivergent synthesis of pyrrolidines bearing two adjacent quaternary stereocenters or two discrete quaternary stereocenters, opening up a new era for medicinal chemistry and diversity-oriented synthesis. DFT calculations showed that the P,N-ligand L2 acts as a pseudobidentate ligand. The formation of a O–Cu bond with the carbonyl oxygen atom of the enone and dissociation of the amine nitrogen of L2 from the Cu(I) center occurs during the catalytic cycle; this is the main reason for the tuning the regioselectivity of the cycloaddition reaction caused by switching of the ligand. The salient features of this work include high yields (up to >99%), a general substrate scope, the use of commercially available ligands, and high...
94 citations
TL;DR: These 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 are described.
Abstract: Catalytic ring opening cross coupling reactions of strained cyclopropanols have been useful for the syntheses of various β-substituted carbonyl products. Among these ring opening cross coupling reactions, the formation of α,β-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,β-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,β-unsaturate...
61 citations
TL;DR: The synthesis of all-carbon tetrasubstituted enones was realized by employing the β-borylated enone unit, without purification, in a Suzuki-Miyaura coupling.
Abstract: Reported is a general procedure to synthesize tetrasubstituted enones, which are borylated in the β-position, using a copper-catalyzed four-component coupling reaction of simple chemical feedstocks: internal alkynes, alkyl halides, bis(pinacolato)diboron (B2 pin2 ), and CO. A broad scope of highly functionalized β-borylated enones, a largely unknown class of organic compounds, can be accessed efficiently using this method. The synthesis of all-carbon tetrasubstituted enones was realized by employing the β-borylated enone unit, without purification, in a Suzuki-Miyaura coupling. The utility of the method was further demonstrated by various transformations, including halogenation, oxidation, and protodeboration, of the corresponding reduced oxaborole species to provide densely substituted allylic alcohol and ketone products.
56 citations
TL;DR: In this article, cyclohexadienones with a flexible ether or alkyl group linked internal enone moiety were constructed and the hydrogen-bonding interaction between thiourea and carbonyl group is crucial and facilitates the otherwise flexible backbones to undergo cyclization.
Abstract: Highly enantioselective intramolecular RC reactions via desymmetrization of cyclohexadienones have been developed. By employing cyclohexadienones with a flexible ether or alkyl group linked internal enone moiety, optically enriched bicyclic pyran and hydrindane skeletons were constructed. Bifunctional phosphine catalysts bearing a thiourea moiety were found to effectively promote the reaction, and preliminary studies suggest that the hydrogen-bonding interaction between thiourea and carbonyl group is crucial and facilitates the otherwise flexible backbones to undergo the desired cyclization.
52 citations
TL;DR: Dose-response studies demonstrated that a range of substituents on the aromatic rings of these enones influenced not only the sensitivity to activation, reflected in EC50 values, but also the extent of activation, which suggests that multiple mechanisms are involved in the activation of Nrf2 by these analogues.
48 citations
TL;DR: A total synthesis of the pyridine-containing limonoid alkaloid (-)-xylogranatopyridine B in 11 steps from commercially available dihydrocarvone is reported.
Abstract: We report a total synthesis of the pyridine-containing limonoid alkaloid (−)-xylogranatopyridine B in 11 steps from commercially available dihydrocarvone. The central pyridine ring was assembled by a late-stage fragment coupling approach employing a modified Liebeskind pyridine synthesis. One fragment was prepared by an allyl-palladium catalyzed oxidative enone β-stannylation, in which the key bimetallic β-stannyl palladium enolate intermediate undergoes a β-hydride elimination. This methodology also allowed introduction of alkyl and silyl groups to the β-position of enones.
46 citations
TL;DR: The first phosphine-catalyzed [5+1] annulation of enones with N-sulfonylimines works efficiently to give tetrahydropyridines.
Abstract: Phosphine-catalyzed [5+1] annulation of δ-sulfonamido-substituted enones with N-sulfonylimines for the synthesis of 1,2,3,6-tetrahydropyridines is developed. The reaction proceeds smoothly under mild reaction conditions to give the annulation products in moderate to excellent yields. Mechanistic exploration of this new annulation shows that the δ-sulfonamido-substituted enone and the N-sulfonylimine serve as C5 and C1 synthons to furnish the annulation, respectively. Using chiral phosphine as the catalyst, an asymmetric variant of the model reaction gave the chiral product in up to 73% ee.
37 citations
TL;DR: Formal Giese addition of C(sp3)–H substrates is achieved by the unprecedented merger of triplet chemistry and Ni catalysis.
Abstract: An unprecedented utilization of triplet excited enones in Ni-catalysis enabled a formal Giese addition of C(sp3)-H nucleophiles. This mechanism-based approach has greatly widened the reaction scope, allowing the synthesis of previously inaccessible structures. In this process, the enone diradical acted as two distinct reaction centers, participating in both metalation and hydrogen atom transfer, ultimately furnishing a range of formal Giese addition products in a highly general context. This reaction provides complementary access to traditional 1,4-addition reactions of enones, with a future perspective to develop triplet diradical-based transition metal catalysis.
30 citations
TL;DR: An asymmetric sulfa-Michael addition of alkyl thiols to enone diesters in high yields and enantioselectivities and generates functionalized lactones with three contiguous stereocenters is reported.
Abstract: An asymmetric sulfa-Michael addition of alkyl thiols to enone diesters is reported. The reaction is catalyzed by a bifunctional triaryliminophosphorane-thiourea organocatalyst and provides a range of α-sulfaketones in high yields and enantioselectivities. Leveraging the gem-diester functional handle via a subsequent diastereotopic group discrimination generates functionalized lactones with three contiguous stereocenters.
29 citations
TL;DR: Curcumin forms the predicted thiol-Michael adducts with three model thiols, glutathione, N-acetylcysteine, and β-mercaptoethanol, and this suggests that protein binding by curcumin may involve oxidative activation into reactive quinone methide and spiroepoxide electrophiles.
Abstract: The polypharmacological effects of the turmeric compound curcumin may be partly mediated by covalent adduction to cellular protein. Covalent binding to small molecule and protein thiols is thought to occur through a Michael-type addition at the enone moiety of the heptadienedione chain connecting the two methoxyphenol rings of curcumin. Here we show that curcumin forms the predicted thiol-Michael adducts with three model thiols, glutathione, N-acetylcysteine, and β-mercaptoethanol. More abundant, however, are respective thiol adducts of the dioxygenated spiroepoxide intermediate of curcumin autoxidation. Two electrophilic sites at the quinone-like ring of the spiroepoxide are identified. Addition of β-mercaptoethanol at the 5′-position of the ring gives a 1,7-dihydroxycyclopentadione-5′ thioether, and addition at the 1′-position results in cleavage of the aromatic ring from the molecule, forming methoxyphenol-thioether and a tentatively identified cyclopentadione aldehyde. The curcuminoids demethoxy- and ...
26 citations
TL;DR: This work marks the first efficient construction of α-diazocarbonyl compounds by phosphine catalysis, and would be furnished in good yields from β-fluoroalkylated β,β-disubstituted enones.
Abstract: An efficient and practical phosphine-catalyzed vicinal difunctionalization of β-fluoroalkyl α,β-enones with TMSN3 has been developed. Using dppb as the catalyst, the reaction worked efficiently to yield various β-amino α-diazocarbonyl compounds in high yields (up to 94 %). This work marks the first efficient construction of α-diazocarbonyl compounds by phosphine catalysis. Meanwhile, the asymmetric variant induced by the nucleophilic bifunctional phosphine P4 led to various chiral fluoroalkylated β-amino α-diazocarbonyl compounds in high yields and enantioselectivity. NMR and ESI-MS studies support the existence of the key reaction intermediates. In contrast, β-azide carbonyl compounds would be furnished in good yields from β-fluoroalkylated β,β-disubstituted enones.
TL;DR: A syn-arylative nickelation followed by nucleophilic syn-selective cyclization of o-propargyloxy benzaldehydes is achieved toward the synthesis of chromanol skeletons with alkenyl substitution at C3 to synthesize 4-alkylated derivatives.
Abstract: A syn-arylative nickelation followed by nucleophilic syn-selective cyclization of o-propargyloxy benzaldehydes is achieved toward the synthesis of chromanol skeletons with alkenyl substitution at C3. The capture of the intermediate vinyl nickel in its cis geometry is done also with a Michael acceptor to synthesize 4-alkylated derivatives. This protocol is equally applicable to o-propargylamino benzaldehydes to access 3,4-disubstituted tetrahydro-hydroquinolines.
TL;DR: Enone carbonyl directed 1,4-addition of ortho-C-H bond in chalcones to maleimides was developed under the catalysis of Rh(III).
Abstract: Enone carbonyl directed 1,4-addition of ortho-C–H bond in chalcones to maleimides was developed under the catalysis of Rh(III). This reaction furnished a variety of chalcone-based pharmacologically useful 3-arylated succinimide derivatives in good yields with excellent selectivity.
TL;DR: Using methanol as a sustainable C1 source, cobalt-catalyzed α-Methoxymethylation and α-aminomethylation of ketones have been developed and an easy way to convert α-methOxymethyl ketones toα-aminometrichyl ketones has been discovered.
TL;DR: This reaction is the first example of a highly selective cross-tetramerization between four different unsaturated compounds and involves partially fluorinated five- and seven-membered nickelacycles as key reaction intermediates.
Abstract: In the presence of a catalytic amount of Ni(cod)2 (cod = 1,5-cyclooctadiene) and PCy3 (Cy = cyclohexyl), the cross-tetramerization of tetrafluoroethylene (TFE), ethylene, alkynes, and aldehydes leads to a variety of fluorine-containing enone derivatives. This reaction is the first example of a highly selective cross-tetramerization between four different unsaturated compounds. Stoichiometric reactions revealed that the present reaction involves partially fluorinated five- and seven-membered nickelacycles as key reaction intermediates.
TL;DR: A highly diastereoselective approach for the rapid construction of an isochroman skeleton was achieved by the copper(ii)-catalyzed transformation of alcohol-tethered enones and diazo compounds.
TL;DR: Bis-(amino)cyclopropenylidene has been utilised as a non-covalent Brønsted base catalyst in the 1,6-conjugate addition of carbon nucleophiles to p-QMs, making it possible to access unsymmetrical diaryl- and triarylmethanes in good to excellent yields.
Abstract: Bis-(amino)cyclopropenylidene has been utilised as a non-covalent Bronsted base catalyst in the 1,6-conjugate addition of carbon nucleophiles to p-QMs. This protocol makes it possible to access unsymmetrical diaryl- and triarylmethanes in good to excellent yields. Further, this catalyst was also explored in the 1,4-conjugate addition of carbon nucleophiles to enone systems.
TL;DR: It is shown that vitamin D analogues designed and synthesized with an electrophile as covalent modifiers for the vitamin D receptor (VDR) show specific VDR-binding potency and agonistic activity, and enone compounds 1 and 2 showed higher reactivity than the ene-ynone 3 and dienone 4 compounds.
Abstract: We designed and synthesized vitamin D analogues with an electrophile as covalent modifiers for the vitamin D receptor (VDR). Novel vitamin D analogues 1-4 have an electrophilic enone group at the side chain for conjugate addition to His301 or His393 in the VDR. All compounds showed specific VDR-binding potency and agonistic activity. Covalent bond formations of 1-4 with the ligand-binding domain (LBD) of VDR were evaluated by electrospray ionization mass spectrometry. All compounds were shown to covalently bind to the VDR-LBD, and the abundance of VDR-LBD corresponding conjugate adducts of 1-4 increased with incubation time. Enone compounds 1 and 2 showed higher reactivity than the ene-ynone 3 and dienone 4 compounds. Furthermore, we successfully obtained cocrystals of VDR-LBD with analogues 1-4. X-ray crystallographic analysis showed a covalent bond with His301 in VDR-LBD. We successfully synthesized vitamin D analogues that form a covalent bond with VDR-LBD.
TL;DR: A dehydrogenative coupling reaction ofcyclic enones of different sizes with substituted thiophenes to construct β-thienyl cyclic enone compounds through palladium-catalyzed C-H functionalization under mild reaction conditions is reported.
TL;DR: A TEMPO-dependent tunable synthesis of functionalized cyclohexa-1,3-dienes and 2-aminobenzophenones/benzoate from the one-pot cascade reactions of allenic ketones/allenoate with amines and enones is presented.
Abstract: A TEMPO-dependent tunable synthesis of functionalized cyclohexa-1,3-dienes and 2-aminobenzophenones/benzoate from the one-pot cascade reactions of allenic ketones/allenoate with amines and enones is presented. Mechanistically, the construction of the entitled six-membered carbocycles involves the in situ generation of an enaminone intermediate via the conjugate addition of allenic ketone with amine followed by its catalyst- and base-free [3+3] annulation with enone along with the simultaneous introduction of the valuable amino and carbonyl groups.
TL;DR: An enantioselective synthesis of Rauhut-Currier (RC) adducts from 3-aryl cyclohexenone with a tethered enone moiety at the ortho-position on the aryl group is accomplished.
TL;DR: An efficient protocol for the synthesis of 2,5-substituted 4-acyloxazoles and the related 2,4-subStituted 5-acyLoxazole with complementary regioselectivity from the corresponding α-oxoketene dithioacetals or β-(het)aryl/(methylthio)enone precursors has been reported.
Abstract: An efficient protocol for the synthesis of 2,5-substituted 4-acyloxazoles and the related 2,4-substituted 5-acyloxazoles with complementary regioselectivity from the corresponding α-oxoketene dithioacetals or β-(het)aryl/(methylthio)enone precursors has been reported. In the first protocol, the α-oxoketene dithioacetals or β-(methylthio)enones were converted to the corresponding α-bromo-β-(methylthio)enones followed by copper catalyzed inter/intramolecular annulation of these intermediates with various primary amides affording 2-(het)aryl/alkyl-4-(het)aroyl-5-(methylthio)/(het)aryloxazoles via concomitant formation of the C4–N and C5–O bond via enamide intermediates. In the second approach, the starting α-oxoketene dithioacetals or β-(methylthio)-β-(het)arylenones were subjected to base induced conjugate addition–elimination with various primary amides to furnish β-aroylenamides, which, on subsequent iodine catalyzed intramolecular oxidative C–H functionalization/C–O bond formation, afforded the correspon...
TL;DR: A total synthesis of the cembranoid (+)-sarcophytin is presented, featuring a Diels-Alder cycloaddition of an enone as the dienophile with an ester-derived dienoate to furnish the cycloadduct, which corrects the previously reported nominal structure.
Abstract: A total synthesis of the cembranoid (+)-sarcophytin is presented, featuring a Diels-Alder cycloaddition of an enone as the dienophile with an ester-derived dienoate. The study highlights a peculiar geometric preference for the Z dienoate to furnish the cycloadduct. The endgame involves a reaction cascade, including lactone opening, alcohol oxidation, and ketone epimerization to complete an efficient synthesis. A salient feature of the synthesis is the resulting reassignment of the absolute configuration, which corrects the previously reported nominal structure.
TL;DR: An asymmetric formal total synthesis of (+)-aplykurodinone-1 was achieved using a route, in which hydrogen bonding serves as a stereochemical control element governing the π-facial selectivity of intramolecular Diels-Alder (IMDA) reaction of an enone tethered 2-pyrone.
TL;DR: The key step in a new synthesis of 2-acetamido-2,3-dideoxy-(1→4)-thiodisaccharides was the conjugate addition of a 1-thiogalactose derivative to E and Z acetyl oximes derived from sugar enones that was shown to be completely diastereoselective for both the formation of the thioglycosidic linkage and the configuration of acetylOxime.
TL;DR: In this article, the enone moiety associated with the biomass-derived, homochiral and now abundant compound levoglucosenone was manipulated to give regio-isomeric mixtures of β,γ-unsaturated malonates or ketones.
TL;DR: In this paper, a series of ferrocenyl ketones were synthesized in reaction with ferrocene and corresponding substituted acryloyl chlorides, following previously described procedure.
TL;DR: In this article, a library of exo-cyclic carbohydrate enones 2−13 were prepared via a base-catalyzed, highly stereoselective aldol condensation of dihydrolevoglucosenone 1 (cyrene) with various aromatic aldehydes.
TL;DR: The catalytic reductive cocyclooligomerization of an enone and three carbene equivalents to generate a cyclopentane is described, a process that constitutes a formal [2 + 1 + 1 -1 + 1]-cycloaddition.
Abstract: Cyclic structures are highly represented in organic molecules, motivating a wealth of catalytic methods targeting their synthesis. Among the various ring-forming processes, cyclooligomerization reactions possess several attractive features but require addressing a unique challenge associated with controlling ring-size selectivity. Here we describe the catalytic reductive cocyclooligomerization of an enone and three carbene equivalents to generate a cyclopentane, a process that constitutes a formal [2 + 1 + 1 + 1]-cycloaddition. The reaction is promoted by a (quinox)Ni catalyst and uses CH2Cl2/Zn as the C1 component. Mechanistic studies are consistent with a metallacycle-based pathway, featuring sequential migratory insertions of multiple carbene equivalents to yield cycloalkanes larger than cyclopropanes.