Showing papers on "Enone published in 2022"
TL;DR: Experimental studies and DFT calculations suggest that an unprecedented intermediate and a new oxidation mode of the NHC-derived Breslow intermediate are involved in the new asymmetric sulfonylation reaction.
Abstract: A carbene-catalyzed sulfonylation reaction between enone aryl aldehydes and sulfonyl chlorides is disclosed. The reaction effectively installs sulfone moieties in a highly enantioselective manner to afford sulfone-containing bicyclic lactones. The sulfonyl chloride behaves both as an oxidant and a nucleophilic substrate (via its reduced form) in this N-heterocyclic carbene (NHC)-catalyzed process. The NHC catalyst provides both activation and stereoselectivity control on a very remote site of enone aryl aldehyde substrates. Water plays an important role in modulating catalyst deactivation and reactivation routes that involve reactions between NHC and sulfonyl chloride. Experimental studies and DFT calculations suggest that an unprecedented intermediate and a new oxidation mode of the NHC-derived Breslow intermediate are involved in the new asymmetric sulfonylation reaction.
20 citations
TL;DR: By employing substrates with subtle structural difference, under virtually identical reaction conditions, the authors were able to access two types of chiral products, which are of biological relevance and synthetic importance.
Abstract: Highly enantioselective and chemodivergent domino reactions between γ-substituted allenoates and activated alkenes have been developed. In the presence of NUSIOC-Phos, triketone enone substrates smoothly reacted with γ-substituted allenoates to form bicyclic furofurans in good yields with high stereoselectivities. Alternatively, the reaction between diester-activated enone substrates and γ-substituted allenoates formed chiral conjugated 1,3-dienes in good yields with excellent enantioselectivities. Notably, by employing substrates with subtle structural difference, under virtually identical reaction conditions, we were able to access two types of chiral products, which are of biological relevance and synthetic importance.
9 citations
TL;DR: In this article , the enantioselective Cu(I)-catalyzed β-borylation/Michael addition on prochiral enone-tethered 2,5-cyclohexadienones was reported.
Abstract: The catalytic asymmetric borylation of conjugated carbonyls followed by stereoselective intramolecular cascade cyclizations with in situ generated chiral enolates are extremely rare. Herein, we report the enantioselective Cu(I)-catalyzed β-borylation/Michael addition on prochiral enone-tethered 2,5-cyclohexadienones. This asymmetric desymmetrization strategy has a broad range of substrate scope to generate densely functionalized bicyclic enones bearing four contiguous stereocenters with excellent yield, enantioselectivity, and diastereoselectivity. One-pot borylation/cyclization/oxidation via the sequential addition of sodium perborate reagent affords the corresponding alcohols without affecting yield and enantioselectivity. The synthetic potential of this reaction is explored through gram-scale reactions and further chemoselective transformations on products. DFT calculations explain the requirement of the base in an equimolar ratio in the reaction, as it leads to the formation of a lithium-enolate complex to undergo C-C bond formation via a chair-like transition state, with a barrier that is 22.5 kcal/mol more favourable than that of the copper-enolate complex.
8 citations
TL;DR: In this article , a deep sea water-derived actinomycete, Actinomadura sp. KD439, was used to identify seven new angucyclinones, designated as kumemicinones A-G (1-7) and miaosporone E.
Abstract: Chemical investigation of the fermentation products of a deep sea water-derived actinomycete, Actinomadura sp. KD439, identified seven new angucyclinones, designated as kumemicinones A-G (1-7), together with the known SF2315B and miaosporone E. NMR and MS spectroscopic analyses, combined with X-ray crystallography and quantum chemical calculations of NMR chemical shifts and electronic circular dichroism (ECD) spectra, uncovered the structures of new angucyclinones as regioisomers of SF2315B at the allyl alcohol unit (1 and 2), an epoxy ring-opened γ-hydroxy enone isomer (3), a B/C-ring-rearranged product (4), or dimers with a new mode of bridging (5-7), adding new structural variation to this antibiotic group. The absolute configuration of SF2315B was also determined by comparison of ECD spectra with those of 1 and 2. All the angucyclinones exhibited cytotoxicity against P388 murine leukemia cells, with IC50 values ranging from 1.8 to 53 μM.
8 citations
TL;DR: A rhodium/chiral diene catalytic system is reported for the reaction of enone-diones and arylboronic acids that allows the switchable synthesis of chiral bicyclic products and acyclic products in a controlled manner.
8 citations
TL;DR: In this article , the enantioselective Cu(I)-catalyzed β-borylation/Michael addition on prochiral enone-tethered 2,5-cyclohexadienones was reported.
Abstract: The catalytic asymmetric borylation of conjugated carbonyls followed by stereoselective intramolecular cascade cyclizations with in situ generated chiral enolates are extremely rare. Herein, we report the enantioselective Cu(I)-catalyzed β-borylation/Michael addition on prochiral enone-tethered 2,5-cyclohexadienones. This asymmetric desymmetrization strategy has a broad range of substrate scope to generate densely functionalized bicyclic enones bearing four contiguous stereocenters with excellent yield, enantioselectivity, and diastereoselectivity. One-pot borylation/cyclization/oxidation via the sequential addition of sodium perborate reagent affords the corresponding alcohols without affecting yield and enantioselectivity. The synthetic potential of this reaction is explored through gram-scale reactions and further chemoselective transformations on products. DFT calculations explain the requirement of the base in an equimolar ratio in the reaction, as it leads to the formation of a lithium-enolate complex to undergo C-C bond formation via a chair-like transition state, with a barrier that is 22.5 kcal/mol more favourable than that of the copper-enolate complex.
7 citations
TL;DR: The first bioinspired, enantioselective, and protecting group free total synthesis of the antibacterial sesquiterpenoid (-)-antroalbocin A (1) has been achieved in 12 steps (5.4% overall yield) from dimedone as mentioned in this paper .
4 citations
TL;DR: In this article, a bis-acrylate functionalized enone derivative (C3POAC) was synthesized and characterized, which is expected to serve not only as a photoinitiator but also as a crosslinker.
4 citations
TL;DR: In this article , a bis-acrylate functionalized enone derivative (C3POAC) was synthesized and characterized, which is expected to serve not only as a photoinitiator but also as a crosslinker.
4 citations
TL;DR: In this paper , cyclohept-2-enone is a reactive dienophile in thermal [4 + 2] cycloaddition reactions with various dienes.
Abstract: Upon irradiation at λ = 350 nm, cyclohept-2-enone undergoes an isomerization to the strained (E)-isomer. The process was studied by XMS-CASPT2 calculations and found to proceed by two competitive reaction channels on either the singlet or the triplet hypersurface. (E)-Cyclohept-2-enone is a reactive dienophile in thermal [4 + 2] cycloaddition reactions with various dienes. Ten different dienes were probed, most of which─except for 1,3-cyclohexadiene─underwent a clean Diels-Alder reaction and gave the respective trans-fused six-membered rings in good yields (68-98%). The reactions with furan were studied in detail, both experimentally and by DLPNO-CCSD(T) calculations. Two diastereoisomers were formed in a ratio of 63/35 with the exo-product prevailing, and the configuration of both diastereoisomers was corroborated by single crystal X-ray crystallography. The outcome of the photoinduced Diels-Alder reaction matched both qualitatively and quantitatively the calculated reaction pathway. Apart from cyclohept-2-enone, five additional cyclic hept-2-enones and cyclooct-2-enone were employed in their (E)-form as dienophiles in the Diels-Alder reaction with 1,3-cyclopentadiene (80-98% yield). The method was eventually applied to a concise total synthesis of racemic trans-α-himachalene (four steps, 14% overall yield).
3 citations
TL;DR: In this article , a simple, highly efficient, and phosphine-free N,C-Ru and N,N-Ru catalysts for ligand-controlled borrowing-hydrogen (BH) and interrupted-borrowing-Hydrogen (I-BH), respectively, were reported.
Abstract: Herein we report simple, highly efficient, and phosphine-free N,C-Ru and N,N-Ru catalysts for ligand-controlled borrowing-hydrogen (BH) and interrupted-borrowing-hydrogen (I-BH) methods, respectively. This protocol has been employed on a variety of ketones using MeOH as a green, sustainable, and alternative C1 source to form a C-C bond through the BH and I-BH methods. Reasonably good substrate scope, functional group tolerance, and good-to-excellent yields at 70 °C are the added highlights of these methodologies. Controlled experiments reveal that an in situ formed formaldehyde is one of the crucial elements in this ligand-controlled selective protocol, which upon reaction with a ketone generates an enone as an intermediate. This enone in the presence of the N,C-Ru catalyst and N,N-Ru catalyst through the BH and I-BH pathways yields methylated ketones and 1,5-diketones, respectively.
TL;DR: In this paper , a weak enone carbonyl/ketone-assisted aerobic C-H olefination of aromatics with unactivated alkenes has been developed.
Abstract: A Rh(III)-catalyzed weak enone carbonyl/ketone-assisted aerobic oxidative C-H olefination of aromatics with unactivated alkenes has been developed. This protocol involves cross-dehydrogenative Heck-type olefination reaction of various substituted biologically relevant chalcones and aromatic ketones such as acetophenones and chromones with various functionalized unactivated olefins in moderate to good yields. Further, ortho-alkylation of chalcones with norbornene is also demonstrated. A possible reaction mechanism involving weak chelation-assisted C-H activation/insertion/β-hydride elimination was proposed and supported by the deuterium labeling studies.
TL;DR: In this article , the highly enantioselective aza-Michael reaction of tert-butyl β-naphthylmethoxycarbamate to cyclic enones has been accomplished by using a new cinchona alkaloid derived C(9)-urea ammonium catalyst under phase-transfer catalysis conditions with up to 98% ee at 0 °C.
TL;DR: In this article , the BC ring moiety of brachialactone, a fusicoccane-type diterpene isolated from the tropical forage grass Brachiaria humidicola and found to inhibit nitrification by soil microbes, is described.
TL;DR: The palladium(0)-catalyzed decarboxylative oxa-Michael addition/remote α-allylation/1,3- migration of prochiral allyl carbonate-tethered cyclohexadienones in good yields is reported.
Abstract: Herein we have reported the palladium(0)-catalyzed decarboxylative oxa-Michael addition/remote α-allylation/1,3- migration of prochiral allyl carbonate-tethered cyclohexadienones in good yields. This unconventional intramolecular rearrangement is triggered by the base-mediated retro-Michael ring-opening reaction (β-elimination) and subsequent syn-selective oxa-Michael addition on the less substituted enone functionality. The generality of tandem decarboxylative allylation was examined with various substrates and in the gram-scale reaction.
TL;DR: The authors achieved a concise total synthesis of salimabromide by using a novel intramolecular radical cyclization to simultaneously construct the unique benzo-fused [4.3.1] carbon skeleton and the vicinal quaternary stereocenters.
Abstract: We achieved a concise total synthesis of salimabromide by using a novel intramolecular radical cyclization to simultaneously construct the unique benzo-fused [4.3.1] carbon skeleton and the vicinal quaternary stereocenters. Other notable transformations include a tandem Michael/Mukaiyama aldol reaction to introduce most of the molecule's structural elements, along with hidden information for late-stage transformations, an intriguing tandem oxidative cyclization of a diene to form the bridged butyrolactone and enone moieties spontaneously, and a highly enantioselective hydrogenation of a cycloheptenone derivative (97% ee) that paved the way for the asymmetric synthesis of salimabromide.
20 Feb 2022
TL;DR: In this paper , a new [Rh(cod)OMe]2 catalyzed 1,2-addition containing (R)-BINAP and different aluminium organyles to cyclic en-1,4-diones was found.
Abstract: The following thesis is divided into two sections. The first part deals with the total synthesis of Mansouramycin A-E. The second part shows a new high enantioselective rhodium catalyzed 1,2-addition of aluminum-organyles to cyclic enones and en-1,4-diones. The Mansouramycines where isolated in the Laatsch group at the department of Chemistry in Göttingen. They show a high cytotoxicity against many human cancer cell lines with an IC50 up to 0.089 μM for lung cancer. The total synthesis started with a Henry reaction of a 2,5-dimethoxybenzaldehyde to give after reduction the corresponding amine. This was cyclized by a Pictet-Spengler reaction and oxidized at palladium to give the isochinoline. After oxidation with CAN the resulting chinolindione was selectively aminated to give the corresponding Mansouramycine in a total yield of 7-32%. A high enantioselektive rhodium catalyzed 1,2-addition of aluminum organyles to cyclic enones and en-1,4-diones was developed in the Zezschwitz group at the university of Marburg. In this thesis a new [Rh(cod)OMe]2 catalyzed 1,2-adition containing (R)-BINAP and different aluminium organyles to cyclic en-1,4-diones was found. The corresponding tertiary alcohols where isolated with an ee up to 98%. The diones could be functionalized at both centres without any 1,4-additions and yields from 40-90% where optained.
TL;DR: In this article , an enone oxidoreductase from Naumovozyma dairenensis CBS 421 (NDEO) was used for HEMF production for the first time.
Abstract: Owing to its unique fragrance, 4-hydroxy-2(or 5)-ethyl-5(or 2)-methyl-3(2H)-furanone (HEMF) is widely used as a food flavoring agent and has high demand. Enone oxidoreductase is a vital enzyme involved in HEMF production. In this study, an enone oxidoreductase from Naumovozyma dairenensis CBS 421 (NDEO) was used for HEMF production for the first time. The mutant NDEOT183W,K290W was obtained through semirational protein engineering, which increased the HEMF yield by 75.2%. Finally, the engineered strain BM4 produced the highest HEMF yield, 194.42 mg L-1 in 132 h. Our study revealed that HEMF production can be improved in Saccharomyces cerevisiae and that this is an efficient method to improve the activity of enone oxidoreductase, which is important for the industrial synthesis of furanone.
TL;DR: In this article , the relative conformation of the C=C and C=O double bonds in the central enone group is s-cisoid ; there is a trans configuration about the C =C bond.
TL;DR: In this article , a dinickel catalyst was used to promote the cycloaddition of two aldehyde equivalents and a vinylidene and the resulting methylenedioxolane products can be deprotected in one pot under acidic conditions to reveal α-hydroxy ketones.
Abstract: A dinickel catalyst promotes the [2 + 2 + 1]-cycloaddition of two aldehyde equivalents and a vinylidene. The resulting methylenedioxolane products can be deprotected in one pot under acidic conditions to reveal α-hydroxy ketones. This method provides convenient access to unsymmetrical alkyl-substituted α-hydroxy ketones, which are challenging to synthesize selectively using cross-benzoin reactions. Mechanistic studies are consistent with an initial migratory insertion of the aldehyde into a dinickel bridging vinylidene. Insertion of the second aldehyde followed by C–O reductive elimination furnishes the cycloadduct. Under dilute conditions, an enone side product is generated due to a competing β-hydride elimination from the proposed metallacyclic intermediate. A DFT model consistent with the concentration-dependent formation of the methylenedioxolane and enone is presented.
TL;DR: A Rh2(esp)2-catalyzed diastereoselective synthesis of highly functionalized β-lactams is developed and extension of this method to the [2+2]-cycloaddition of PMB-protected imines and diazoacetoacetate enones catalyzed by Rh2
Abstract: A Rh2(esp)2-catalyzed diastereoselective synthesis of highly functionalized β-lactams is developed. By employing Rh2(esp)2 as the catalyst, a reaction cascade operates by reducing an N-methyl nitrone to the corresponding N-methyl imine in the presence of a first molecule of the diazoacetoacetate enone. A second molecule of the diazoacetoacetate enone sensing a change in the reaction medium undergoes a Wolff rearrangement to afford a vinyl ketene. This vinyl ketene then reacts with the in situ generated N-methyl imine to diastereoselectively furnish a β-lactam with two contiguous stereogenic centers. Extension of this method to the [2+2]-cycloaddition of PMB-protected imines and diazoacetoacetate enones catalyzed by Rh2(esp)2 is also reported.
TL;DR: A Diels-Alder reaction leading to 4-nitrophenylcyclohexanones followed by base-mediated reductive cyclization of the resulting ketone tethered to the nitrobenzene moiety gives access to the hexahydro-2,6-methano-1-benzazocine ring system present in several biologically interesting natural products such as aspernomine as discussed by the authors .
Abstract: A Diels–Alder reaction leading to 4-nitrophenylcyclohexanones followed by a newly developed base-mediated reductive cyclization of the resulting ketone tethered to the nitrobenzene moiety gives access to the hexahydro-2,6-methano-1-benzazocine ring system present in several biologically interesting natural products such as aspernomine. The scope of the reaction was explored with eight substituted nitrobenzenes, obtaining yields of up to 87%. The highest cytotoxicity was observed in benzazocine 4h, bearing an enone moiety, which was active against eight cancer cell lines.
TL;DR: The first total synthesis of penicyclone A, a novel deep-sea fungus-derived polyketide, and a reevaluation of its antimicrobial activity was described in this paper .
Abstract: We describe the first total synthesis of penicyclone A, a novel deep-sea fungus-derived polyketide, and a reevaluation of its antimicrobial activity. The synthesis of this unique spirolactone was achieved in 10 steps starting from a known d-ribose derivative. The key steps include a double Grignard reaction for the diastereoselective construction of the chiral tertiary alcohol intermediate, tandem oxidation/cyclization, and photooxygenation, followed by an oxidative rearrangement to introduce the enone functionality.
TL;DR: In this paper , a two-carbon insertion into β-ketoesters with vinylmetal has been developed for the rapid synthesis of δ-ketoeppers, which features high efficiency, simple operation, and mild conditions without the usage of bases and catalysts.