Showing papers on "Enone published in 2016"
TL;DR: This Review provides an overview of reported methods for enantioselective and asymmetric syntheses of cyclopentenones, including chemical and enzymatic resolution, asymmetric synthesis via Pauson-Khand reaction, Nazarov cyclization and organocatalyzed reactions, asymmetrical functionalization of the existing cyclopENTenone unit, andfunctionalization of chiral building blocks.
Abstract: The cyclopentenone unit is a very powerful synthon for the synthesis of a variety of bioactive target molecules. This is due to the broad diversity of chemical modifications available for the enone structural motif. In particular, chiral cyclopentenones are important precursors in the asymmetric synthesis of target chiral molecules. This Review provides an overview of reported methods for enantioselective and asymmetric syntheses of cyclopentenones, including chemical and enzymatic resolution, asymmetric synthesis via Pauson-Khand reaction, Nazarov cyclization and organocatalyzed reactions, asymmetric functionalization of the existing cyclopentenone unit, and functionalization of chiral building blocks.
174 citations
TL;DR: The first copper-catalyzed direct β-functionalization of saturated ketones is reported, which proceeds via a novel radical-based dehydrogenation to enone and subsequent conjugate addition sequence.
Abstract: The first copper-catalyzed direct β-functionalization of saturated ketones is reported. This protocol enables diverse ketones to couple with a wide range of nitrogen, oxygen and carbon nucleophiles in generally good yields under operationally simple conditions. The detailed mechanistic studies including kinetic studies, KIE measurements, identification of reaction intermediates, EPR and UV–visible experiments were conducted, which reveal that this reaction proceeds via a novel radical-based dehydrogenation to enone and subsequent conjugate addition sequence.
138 citations
TL;DR: In this paper, the possible reaction mechanisms and origin of stereoselectivity in the reaction between saturated carbonyl compounds with enones generating cyclopentenes catalyzed by N-heterocyclic carbene (NHC) were investigated using density functional theory.
Abstract: Activation of inert sp3 β-C–H bonds has attracted widespread attention and been developed with significant progress in recent years, but understanding the mechanism of this kind of reaction continues to be one of the most challenging topics in organic chemistry. In this paper, the possible reaction mechanisms and origin of stereoselectivity in the reaction between saturated carbonyl compounds with enones generating cyclopentenes catalyzed by N-heterocyclic carbene (NHC) have been investigated using density functional theory. The computational results show that the additive DBU plays an important role in NHC-catalyzed C–H activation. Analyses of the natural bond orbital charge and global reaction index indicate that NHC can lower the energy barrier of the entire reaction by activating the α/β-C–H bond rather than by strengthening the nucleophilicity of the reactant as a Lewis base. This is remarkably at variance from previous reports. In addition, the π···π stacking between the phenyl of the enone and the ...
97 citations
TL;DR: Rh(iii)-catalyzed cascade addition of C–H bonds across alkene and carbonyl π-bonds to form two new σ C–C bonds is accomplished.
Abstract: The Rh(III)-catalyzed cascade addition of a C–H bond across alkene and carbonyl π-bonds is reported. The reaction proceeds under mild reaction conditions with low catalyst loading. A range of directing groups were shown to be effective as was the functionalization of alkenyl in addition to aromatic C(sp2)–H bonds. When the enone and aldehyde electrophile were tethered together, cyclic β-hydroxy ketones with three contiguous stereocenters were obtained with high diastereoselectivity. The intermolecular three-component cascade reaction was demonstrated for both aldehyde and imine electrophiles. Moreover, the first X-ray structure of a cationic Cp*Rh(III) enolate with interatomic distances consistent with an η3-bound enolate is reported.
84 citations
TL;DR: In this paper, a new model for asymmetric conjugate addition of aromatic thiols to cycloalkenones was proposed, based on quantum mechanics, which rationalizes the stereoselective outcome of Wynberg's reaction.
Abstract: Wynberg's report from 1977 that natural cinchona alkaloids catalyze the asymmetric conjugate addition of aromatic thiols to cycloalkenones is a landmark discovery in hydrogen bonding organocatalysis. Wynberg proposed that this reaction proceeded via the formation of a thiolate-alkylammonium tight ion pair and activation of the enone electrophile by a hydrogen bond from the catalyst's hydroxyl group. This reaction model provided the mechanistic basis for understanding Wynberg's reaction and many other asymmetric transformations since. Our quantum mechanical calculations reveal a different model should be used to explain the results: the alkylammonium ion activates the enone by Bronsted acid catalysis, and the catalyst's hydroxyl group orients the thiolate nucleophile. The new model rationalizes the stereoselective outcome of Wynberg's reaction and provides a new, general model for asymmetric cinchona organocatalysis.
67 citations
TL;DR: The first total synthesis of the alkaloid (-)-haliclonin A is reported, which relied on a novel organocatalytic asymmetric conjugate addition of nitromethane with 3-alkenyl cyclohex-2-enone to set the stereochemistry of the all-carbon quaternary stereogenic center.
Abstract: The first total synthesis of the alkaloid (−)-haliclonin A is reported. The asymmetric synthesis relied on a novel organocatalytic asymmetric conjugate addition of nitromethane with 3-alkenyl cyclohex-2-enone to set the stereochemistry of the all-carbon quaternary stereogenic center. The synthesis also features a Pd-promoted cyclization to form the 3-azabicyclo[3,3,1]nonane core, a SmI2-mediated intermolecular reductive coupling of enone with aldehyde to form the requisite secondary chiral alcohol, ring-closing alkene and alkyne metathesis reactions to build the two aza-macrocyclic ring systems, and an unprecedented direct transformation of enol into enone.
51 citations
TL;DR: An unprecedented sequential gold-catalyzed enone-formation and bifunctional tertiary amine mediated asymmetric cyanosilylation reaction is developed, allowing the highly enantioselective synthesis of 3-alkenyloxindole from diazooxindoles, furans and trimethylsilyl cyanide (TMSCN).
47 citations
TL;DR: This is the first enantioselective β-elimination reaction catalyzed by a chiral cation-binding polyether and allows an effective recycling and overall synthesis of chiral β-sulfonyl ketones in high yield and excellent enantiOSElectivity.
Abstract: Reported herein is the first enantioselective β-elimination reaction catalyzed by a chiral cation-binding polyether. By using this catalytic protocol, a wide range of β-sulfonyl ketones could be effectively resolved with high stereoselectivity (S up to >300). Key to the success of this process is the favorable secondary interactions of the catalyst with the Lewis basic groups on the sulfone substrate. The enone product of this process can be easily converted into the racemic starting material, and allows an effective recycling and overall synthesis of chiral β-sulfonyl ketones in high yield and excellent enantioselectivity.
45 citations
TL;DR: The synthetic utility of the α-amino enone products is demonstrated in a short enantioselective synthesis of the natural product sphingosine.
Abstract: Readily available α-amino aldehydes, incorporating a methylthiomethyl (MTM) protecting group on nitrogen, are shown to be efficient substrates in Rh-catalyzed alkyne hydroacylation reactions. The reactions are performed under mild conditions, employing a small-bite-angle bis-phosphine ligand, allowing for good functional group tolerance with high stereospecificity. Amino aldehydes derived from glycine, alanine, valine, leucine, phenylalanine, isoleucine, serine, tryptophan, methionine, and cysteine were successfully employed, as was an enantiomerically enriched α-OMTM-aldehyde derived from phenyllactic acid. The synthetic utility of the α-amino enone products is demonstrated in a short enantioselective synthesis of the natural product sphingosine.
42 citations
TL;DR: In this article, the effects of chemical composition and pretreatment on Mg-Al hydrotalcites and alumina-supported MgO were evaluated for the gas-phase, self-condensation reaction of C3-C5 biomass-derived methyl ketones.
Abstract: The effects of chemical composition and pretreatment on Mg–Al hydrotalcites and alumina-supported MgO were evaluated for the gas-phase, self-condensation reaction of C3–C5 biomass-derived methyl ketones. We show that the selectivity toward the acyclic dimer enone and the cyclic enone trimer can be tuned by controlling the temperature of hydrotalcite calcination. Methyl ketone cyclization is promoted by Lewis acidic sites present on the hydrotalcite catalysts. XRD and thermal decomposition analysis reveal that the formation of periclase MgO starts above 623 K accompanied by complete disappearance of the hydrotalcite structure and is accompanied by an increase in hydroxyl condensation as the formation of well-crystallized periclase. 27Al MQMAS and 25Mg MAS NMR show that at progressively higher temperatures, Al3+ cations diffuses out of the octahedral brucite layers and incorporate into the tetrahedral and octahedral sites of the MgO matrix thereby creating defects to compensate the excess positive charge ge...
33 citations
TL;DR: The key core of this alkaloid was constructed through a phosphoric acid promoted and highly stereocontrolled alkyne aza-Prins cyclization reaction, synchronously establishing the bridged B-ring and the C13 quaternary stereocenter.
TL;DR: These syntheses enable the scalable preparation of the Kopsia alkaloids for biological studies and confirmed the absolute stereochemistry of both natural products.
Abstract: Enantioselective total syntheses of the Kopsia alkaloids (+)-grandilodine C and (+)-lapidilectine B were accomplished. A key intermediate, spirodiketone, was synthesized in 3 steps and converted into the chiral enone by enantioselective deprotonation followed by oxidation with up to 76 % ee. Lactone formation was achieved through stereoselective vinylation followed by allylation and ozonolysis. The total synthesis of (+)-grandilodine C was achieved by palladium-catalyzed intramolecular allylic amination and ring-closing metathesis to give 8- and 5-membered heterocycles, respectively. Selective reduction of a lactam carbonyl gave (+)-lapidilectine B. The absolute stereochemistry of both natural products was thereby confirmed. These syntheses enable the scalable preparation of the above alkaloids for biological studies.
TL;DR: The fused 6/7/5/6/ 6/6-membered (ABCDE) ring system of talatisamine was synthesized in 22 steps and the radical and cationic cyclizations were demonstrated to be highly chemoselective, and they significantly contributed to streamlining the route to the intricately fused pentacycle of Talatisamine.
Abstract: The fused 6/7/5/6/6-membered (ABCDE) ring system of talatisamine was synthesized in 22 steps. After preparation of the AE-ring structure from 2-(ethoxycarbonyl)cyclohexanone, elaboration of the carboskeleton was realized by sequential additions of allyl magnesium bromide and the lithiated C-ring. The C11-bridgehead radical derived from the ACE-ring underwent the 7-endo cyclization with the enone moiety to form the B-ring in C10-stereoselective and C11-stereospecific manners. The 6-endo cyclization of the remaining D-ring was in turn attained by using the silyl enol ether as the nucleophile and the PhSeCl-activated olefin as the electrophile. These radical and cationic cyclizations were demonstrated to be highly chemoselective, and they significantly contributed to streamlining the route to the intricately fused pentacycle of talatisamine.
TL;DR: The origin of stereoselectivity in the (3+2) annulation of allenes and enones catalyzed by an amino acid derived phosphine catalyst has been investigated by the use of dispersion-corrected density functional theory.
Abstract: The origin of stereoselectivity in the (3+2) annulation of allenes and enones catalyzed by an amino acid derived phosphine catalyst has been investigated by the use of dispersion-corrected density functional theory. An intermolecular hydrogen bond between the intermediate zwitterion and the enone was found to be the key interaction in the two enantiomeric transition states. Additional stabilization is provided by intermolecular hydrogen-bonding interactions between acidic positions on the catalyst backbone and the substrate. Enantioselectivity occurs because the intermolecular hydrogen bond in the transition state leading to the minor enantiomer is only possible at the expense of reactant distortion.
TL;DR: In this paper, the use of either 1,3-dicarbonyls, acyl benzothiazoles, or acyl benimidazoles as nucleophiles allows three distinct, diastereodivergent domino reaction pathways to be accessed to form various fused polycyclic cores containing multiple contiguous stereocentres.
Abstract: α,β-Unsaturated acyl ammoniums generated from the reaction of α,β-unsaturated 2,4,6-trichlorophenol (TCP) esters bearing a pendent enone with an isothiourea organocatalyst are versatile intermediates in a range of enantioselective nucleophile-dependent domino processes to form complex products of diverse topology with excellent stereoselectivity. Use of either 1,3-dicarbonyls, acyl benzothiazoles, or acyl benzimidazoles as nucleophiles allows three distinct, diastereodivergent domino reaction pathways to be accessed to form various fused polycyclic cores containing multiple contiguous stereocentres.
TL;DR: A total synthesis of the highly strained natural product aquatolide has been achieved and the eight-membered enone was built by a late-stage intramolecular Nozaki-Hiyama-Kishi vinylation reaction of steric bulky vinyl iodide and aldehyde.
TL;DR: The described chemistry sets the stage for large-scale production of Δ(12) -PGJ3 and designed analogues for further biological and pharmacological studies are designed.
Abstract: The total synthesis of Δ(12) -prostaglandin J3 (Δ(12) -PGJ3 , 1), a reported leukemia stem cell ablator, through a number of strategies and tactics is described. The signature cross-conjugated dienone structural motif of 1 was forged by an aldol reaction/dehydration sequence from key building blocks enone 13 and aldehyde 14, whose lone stereocenters were generated by an asymmetric Tsuji-Trost reaction and an asymmetric Mukaiyama aldol reaction, respectively. During this program, a substituent-governed regioselectivity pattern for the Rh-catalyzed C-H functionalization of cyclopentenes and related olefins was discovered. The evolution of the synthesis of 1 from the original strategy to the final streamlined process proceeded through improvements in the construction of both fragments 13 and 14, exploration of the chemistry of the hitherto underutilized chiral lactone synthon 57, and a diastereoselective alkylation of a cyclopentenone intermediate. The described chemistry sets the stage for large-scale production of Δ(12) -PGJ3 and designed analogues for further biological and pharmacological studies.
TL;DR: An "on water" hydroquinine-based primary amine-benzoic acid organocatalyst system was found to be best suited to produce 3,4,5-trisubstituted cyclohexanones with a nitro group in the 4-position from enones and nitro dienes under ambient conditions in good yield, with good diastereoselectivity, and with excellent enantioselectivities.
TL;DR: In this article, an asymmetric asymmetric domino reaction of γ-nitro ketones and enones has been developed for the construction of functionalized cyclohexane skeletons with four stereogenic carbon atoms, including one tetrasubstituted carbon stereocenter.
TL;DR: The isothiourea-catalysed enantioselective synthesis of cis-pyrrolizines is explored synthetically and computationally.
Abstract: The catalytic enantioselective synthesis of a range of cis-pyrrolizine carboxylate derivatives with outstanding stereocontrol (14 examples, >95 : 5 dr, >98 : 2 er) through an isothiourea-catalyzed intramolecular Michael addition-lactonisation and ring-opening approach from the corresponding enone acid is reported. An optimised and straightforward three-step synthetic route to the enone acid starting materials from readily available pyrrole-2-carboxaldehydes is delineated, with benzotetramisole (5 mol%) proving the optimal catalyst for the enantioselective process. Ring-opening of the pyrrolizine dihydropyranone products with either MeOH or a range of amines leads to the desired products in excellent yield and enantioselectivity. Computation has been used to probe the factors leading to high stereocontrol, with the formation of the observed cis-steroisomer predicted to be kinetically and thermodynamically favoured.
TL;DR: A palladium‐catalyzed oxidative functionalization of alkynes to generate α‐acetoxylated enones in one step is reported, and a range of functional groups are well‐tolerated in this reaction.
Abstract: We report a palladium-catalyzed oxidative functionalization of alkynes to generate α-acetoxylated enones in one step. A range of functional groups are well-tolerated in this reaction. Mechanistic studies, including the use of (18) O-labeled DMSO, revealed that the ketone oxygen atom in the product originates from DMSO.
TL;DR: A radical-based strategy for regioselective γ-C-C bond formation/oxa-conjugate addition, forming the tetrahydrobenzofuran core common to many bioactive natural products is described.
Abstract: A radical-based strategy for regioselective γ-C-C bond formation/oxa-conjugate addition, forming the tetrahydrobenzofuran core common to many bioactive natural products is described. The technique utilizes readily available enone derivatives and 1,3-dicarbonyl compounds as coupling partners in an oxidative formal [3+2] cycloaddition mediated by Mn(III) . The transformation delivers polycyclic products in good yields and proceeds with complete regiocontrol and excellent stereoselectivity. Sterically encumbered substrates are notably well-tolerated and bond formation occurs readily to form neopentyl and all-carbon quaternary centers in good yields. Several stereo- and chemoselective transformations of the products are described.
TL;DR: An expedient approach to highly functionalized cis- and trans-decalines that could function as key structural subunits toward the synthesis of various classes of terpenoids is reported.
Abstract: We report an expedient approach to highly functionalized cis- and trans-decalines that could function as key structural subunits toward the synthesis of various classes of terpenoids. Key to the strategy is an organocatalyzed Robinson annulation reaction of the Nazarov reagent that affords chiral enone building blocks with high enantioselectivities. The quaternary carbon stereogenic center can direct the subsequent reactions and allow the rapid and diastereoconvergent assembly of complex decalines with contiguous stereocenters.
TL;DR: Carbonyl compounds bearing a γ-amino group are valuable pharmacologically active targets and the amination reaction occurs readily with sterically demanding nucleophiles and is stereoselective.
TL;DR: The multiconfiguration perturbation theory associated with energy-consistent relativistic pseudopotentials offers a mechanistic comparison between representative coumarin and enone substrates for asymmetric catalysis of the intramolecular enone photocycloaddition reaction.
Abstract: The asymmetric catalysis of the intramolecular enone [2 + 2] photocycloaddition reaction relies on a complicated regulation mechanism to control its reactivity and selectivity as well as quantum yield. The multiconfiguration perturbation theory associated with energy-consistent relativistic pseudopotentials offers a mechanistic comparison between representative coumarin and enone substrates. A pair of bright ππ* states govern the unselective background reaction of the free coumarin through the direct cycloaddition in the singlet hypersurface and the elimination of the reaction channel in the triplet manifold due to the existence of anti El Sayed type singlet–triplet crossing. The opening of a reaction channel in the triplet state is repeatedly verified to depend on the presence of relativistic effects, i.e., spin–orbit coupling due to heavy atoms in the chiral Lewis acid catalyst.
TL;DR: Light-induced transformation of atropisomeric and achiral enones displays divergent reactivity and selectivity and detailed photochemical, photophysical, and theoretical investigations have provided insight.
Abstract: Light-induced transformation of atropisomeric and achiral enones displays divergent reactivity. Photocyclization leading to 3,4-dihydroquinolin-2-one was observed with achiral enone carboxamide, whereas the atropisomeric enone carboxamides underwent hydrogen abstraction leading to spiro-β-lactams. Detailed photochemical, photophysical, and theoretical investigations have provided insight into this divergent reactivity and selectivity.
TL;DR: The direct oxidative coupling strategy for ligation of the core of propindilactone G with its side chain may find application in the syntheses of other natural products and complex molecules.
Abstract: Two independent synthetic approaches were evaluated for the final phase of the asymmetric total synthesis of propindilactone G (1). The key steps that led to the completion of the asymmetric total synthesis included: 1) an intermolecular oxidative heterocoupling reaction of enolsilanes to link the core structure to the side chain; 2) an intermolecular Wittig reaction for the formation of the α,β,γ,δ-unsaturated ester; and 3) a regio- and stereoselective OsO4 -catalyzed dihydroxylation of an α,β,γ,δ-unsaturated enone, followed by an intramolecular lactonization reaction to afford the final product. These reactions enabled the synthesis of (+)-propindilactone G in only 20 steps. As a consequence of our synthetic studies, the structure of (+)-propindilactone G has been revised. Furthermore, the direct oxidative coupling strategy for ligation of the core of propindilactone G with its side chain may find application in the syntheses of other natural products and complex molecules.
TL;DR: This is the first example of transition metal-catalyzed enaminone C-N bond conversion for the generation of a new C-C(aryl) structure.
Abstract: The syntheses of β,β-diaryl aryl propiophenones have been realized via palladium-catalyzed domino reactions of dimethyl amino functionalized enaminones and aryl boronic acids. This is the first example of transition metal-catalyzed enaminone C–N bond conversion for the generation of a new C–C(aryl) structure.
TL;DR: Catalytic asymmetric three-component coupling reactions of terminal alkynes, α,β-unsaturated ketones, and aldehydes were studied to produce various functional molecules from commercially available substrates in a one-pot procedure with moderate to good enantioselectivities.
Abstract: Catalytic asymmetric three-component coupling reactions of terminal alkynes, α,β-unsaturated ketones, and aldehydes were studied. The chiral ruthenium complexes containing bis(oxazolinyl)phenyl ligands were found to serve as efficient catalysts for a tandem reaction based on conjugate addition of terminal alkynes to α,β-unsaturated ketones and subsequent aldol reaction with aldehydes, giving β-hydroxyketone derivatives containing α-propargyl groups in high yields with moderate to good enantioselectivities. This method can produce various functional molecules from commercially available substrates in a one-pot procedure. The absolute configuration of the major product was determined by X-ray analysis. The control experiments suggested that a ruthenium enolate species generated in situ by conjugate addition could be involved as an intermediate for the aldol coupling with an aldehyde.
TL;DR: A direct enantioselective reaction of cyclopent-2-enone-derived Morita–Baylis–Hillman alcohols with 4-hydroxycoumarins has been developed under the catalysis of a chiral primary amine derived from cinchonine in combination with a Bronsted acid.
Abstract: A direct enantioselective reaction of cyclopent-2-enone-derived Morita–Baylis–Hillman alcohols with 4-hydroxycoumarins has been developed under the catalysis of a chiral primary amine derived from cinchonine in combination with a Bronsted acid. The reaction provides pyranocoumarin products with three vicinal chiral carbon centers in highly regio-, diastereo- and enantioselectivities through a tandem allylic alkylation/intramolecular oxa-Michael addition.