Showing papers on "Enone published in 2006"
TL;DR: The first enantioselective organocatalytic transfer hydrogenation of cyclic enones has been accomplished and the sense of asymmetric induction is in complete accord with the stereochemical model first reported in conjunction with the use of catalyst 4 for enantiOSElective ketone Diels-Alder reactions.
Abstract: The first enantioselective organocatalytic transfer hydrogenation of cyclic enones has been accomplished. The use of iminium catalysis has provided a new organocatalytic strategy for the enantioselective reduction of β,β-substituted α,β-unsaturated cycloalkenones, to generate β-stereogenic cyclic ketones. The use of imidazolidinone 4 as the asymmetric catalyst has been found to mediate the hydrogenation of a large class of enone substrates with tert-butyl Hantzsch ester serving as an inexpensive source of hydrogen. The capacity of catalyst 4 to enable enantioselective transfer hydrogenation of cycloalkenones has been extended to five-, six-, and seven-membered ring systems. The sense of asymmetric induction is in complete accord with the stereochemical model first reported in conjunction with the use of catalyst 4 for enantioselective ketone Diels−Alder reactions.
192 citations
178 citations
TL;DR: A series of 2- and 3-alkyl-substituted 2-cyclohexenones were shown to be substrates for the old yellow enzyme of Saccharomyces carlsbergensis expressed in Escherichia coli cells, supporting the notion that enzymes of this family may be useful in stereoselective organic synthesis.
Abstract: A series of 2- and 3-alkyl-substituted 2-cyclohexenones were shown to be substrates for the old yellow enzyme of Saccharomyces carlsbergensis expressed in Escherichia coli cells. Chemo- and stereoselective alkene reductions were observed, and the absolute configurations of the products could be predicted from the X-ray crystal structure of the protein. No competing carbonyl reductions were detected. These results support the notion that enzymes of this family may be useful in stereoselective organic synthesis.
86 citations
TL;DR: A series of neutral Ni(II) complexes derived from anilino-substituted enone ligands bearing electron-withdrawing trifluoromethyl groups have been synthesized and characterized in this paper.
75 citations
TL;DR: The first key step, tandem closure in which stereochemistry is controlled by geometric constraints, was followed by an unprecedented reductive hydroamination, completing the synthesis of (-)-dihydroisocodeine ((-)-17) in 13 steps from commercially available materials.
Abstract: [reaction: see text] The radical cyclization approach to the morphine alkaloids has been applied in an asymmetric synthesis of (-)-dihydrocodeinone. A chiral cyclohexenol (R-32), from the CBS reduction of the enone, is the source of chirality. The first key step, tandem closure in which stereochemistry is controlled by geometric constraints, (-)-15b --> (+)-16, was followed by an unprecedented reductive hydroamination, completing the synthesis of (-)-dihydroisocodeine ((-)-17) in 13 steps from commercially available materials.
73 citations
TL;DR: An approach to the total synthesis of the antimicrotubule agent welwistatin is described and key transformations include an intramolecular cyclization of acetic acid derivative 18 to give rise to indole 19.
72 citations
TL;DR: In this article, the authors describe the total synthesis of (+)- and (−)-galbulimima alkaloid 13 and describe the CDE-ring system in complex galbulimma alkaloids with complete diastereoselection.
Abstract: We describe the total synthesis of (+)- and (−)-galbulimima alkaloid 13. The absolute stereochemistry of natural (−)-galbulimima alkaloid 13 is revised to 2S. Sequential use of catalytic cross-coupling and cross-metathesis reactions followed by an intramolecular Diels−Alder reaction provided the required trans-decalin AB-ring system and masked the C16 carbonyl as an N-vinyl carbamate for late-stage unveiling in the form of the necessary C16 enone. A vinyl radical cyclization secured the C-ring, while successful execution of our strategy for introduction of the CDE-ring system in complex galbulimima alkaloids provided the target pentacycle with complete diastereoselection.
71 citations
TL;DR: The use of beta-S-substituted aldehydes in rhodium-catalyzed intermolecular hydroacylation reactions is reported, and the reactions with electron-poor alkenes and alkynes provide enone products with excellent selectivity for the E-isomers.
Abstract: The use of β-S-substituted aldehydes in rhodium-catalyzed intermolecular hydroacylation reactions is reported. Aldehydes substituted with either sulfide or thioacetal groups undergo efficient hydroacylation with a variety of electron-poor alkenes, such as enoates, in Stetter-like processes and with both electron-poor and neutral alkynes. In general, the reactions with electron-poor alkenes demonstrate good selectivity for the linear regioisomer, and the reactions with alkynes provide enone products with excellent selectivity for the E-isomers. The scope of the process was shown to be broad, tolerating a variety of substitution patterns and functional groups on both reaction components. A novel CN-directing effect was shown to be responsible for reversing the regioselectivity in a number of alkyne hydroacylation reactions. Catalyst loadings as low as 0.1 mol % were achievable.
67 citations
TL;DR: The potential of photomediated reactions for the generation of radicals from unusual precursors and the synthetic significance of this method are discussed in this paper, where the synthesis of β-cycloalkylketones is discussed.
57 citations
TL;DR: The conjugate addition of alkynylboronates to enones catalyzed by binaphthols has been studied theoretically with DFT methods and the competing hetero-Diels-Alder reactions are computed to be kinetically disfavored relative to alkynyborations.
Abstract: The conjugate addition of alkynylboronates to enones catalyzed by binaphthols has been studied theoretically with DFT methods. The high reactivity of the alkynylboronate derived from binaphthol seems to arise from electronic effects since its acidic boron atom binds tightly to the enone carbonyl and lowers the activation energy of the alkynylboration step. Steric clashes between the atoms of the ligands on boron and the enone can be invoked to account for the observed facial diastereoselectivity. The competing hetero-Diels−Alder reactions are computed to be kinetically disfavored relative to alkynylborations.
54 citations
TL;DR: In this paper, an enantioselective synthesis of acyclic β-diaryl ketones and esters via 1,4-addition of arylboronic acids to β-aryl-α,β-unsaturated ketones or esters is described.
TL;DR: A convenient method for the preparation of 5-hydroxy-5-trihalo-4,5-dihydroisoxazoles and beta-enamino trihalomethyl ketones from the reaction of 1,1,1-triHalo- 4-alkoxy-3-alken-2-ones with hydroxylamine and anilines using water as solvent and under ultrasound irradiation is reported.
TL;DR: A carbonyl ylide cycloaddition approach to the squalene synthase inhibitors zaragozic acids A and C is described.
Abstract: A carbonyl ylide cycloaddition approach to the squalene synthase inhibitors zaragozic acids A and C is described. The carbonyl ylide precursor 8 was synthesized starting from di-tert-butyl D-tartrate (47) via an eleven-step sequence involving the regioselective reduction of the mono-MPM (MPM = 4-methoxybenzyl) ether 48 with LiBH4 and the diastereoselective addition of sodium tert-butyl diazoacetate to α-keto ester 10. The reaction of α-diazo ester 8 with 3-butyn-2-one (40) in the presence of a catalytic amount of [Rh2(OAc)4] gave the desired cycloadduct 59 as a single diastereomer. The dihydroxylation of enone 59 followed by sequential transformations permitted the construction of the fully functionalized 2,8-dioxabicyclo[3.2.1]octane core 5. Alkene 79 derived from 5 serves as a common precursor to zaragozic acids A (1) and C (2), since the elongation of the C1 alkyl side chain can be attained by olefin cross-metathesis, especially under the influence of Blechert's catalyst (85).
TL;DR: In this paper, a cyclopentenone possessing the α-chain at the γ position was transformed in five steps into the key cyclopentinone possessing α-chains at the α position.
TL;DR: In this paper, aryl transfer to the transiently generated (β-phosphonio)enolate to provide α-arylated enone was proposed, which represents a regiochemical complement to the Mizoroki-Heck arylation, and is used strategically in concise formal and enantioselective total syntheses of the blockbuster antidepressant (−)-paroxetine (PAXIL).
TL;DR: In this article, the sulfur linkage of β-(14)-thiodisaccharides was constructed with excellent diastereoselectivity by Michael addition of 2,3,4,6-tetra-O-acetyl-1-thio-β-D-galactose or its β-Dglucose isomer to sugar-derived (2S, 6S)-6-acetoxymethyl-2-(2-propyloxy)-2H-pyran-3(6H)-one.
TL;DR: A study of the effect of Michael acceptor stereochemistry on the efficiency of intramolecular Morita-Baylis-Hillman reactions has been performed, and it is proposed that steric effects are a possible source of this dramatic difference in reactivity.
Abstract: A study of the effect of Michael acceptor stereochemistry on the efficiency of intramolecular Morita−Baylis−Hillman (MBH) reactions has been performed. The reactions were catalyzed by a phosphine, and the reaction substrates studied were enones containing a pendant aldehyde moiety attached at the β-position of the alkene group. In all cases examined with PPh3 as the catalyst, cyclization substrates possessing (Z)-alkene stereochemistry afforded a much higher yield of the desired product than did the E isomeric substrates under identical reaction conditions. This was also true when a polymer-supported phosphine catalyst was used. While both alkene isomers afforded the same product, in parallel reactions, the Z isomer afforded 2.5−8.5 times higher yield than did the corresponding E isomer. It is proposed that steric effects are a possible source of this dramatic difference in reactivity. Substrates where the β-substituent is cis to the electron-withdrawing substituent are relatively more accessible to react...
TL;DR: In this article, the authors proposed a 12-step naphthaldehyde synthesis with a high yield of 9.5% using an aryne cycloaddition and a subsequent regioselective ring-opening of the tricyclic adduct.
TL;DR: A modular asymmetric synthesis of medium-sized carbocycles and lactones has been developed that affords highly substituted 7-, 9-, and 11-membered rings.
Abstract: A modular asymmetric synthesis of medium-sized carbocycles and lactones has been developed that affords highly substituted 7-, 9-, and 11-membered rings. The key steps are (1) the highly diastereoselective synthesis of sulfoximine-substituted homoallylic alcohols from allylic sulfoximines and unsaturated as well as saturated aldehydes, (2) an E-stereoselective alkylation and hydroxyalkylation of sulfoximine-substituted alkenyllithium derivatives, (3) the esterification of sulfoximine-substituted homoallylic alcohols, and (4) the ring-closing metathesis reaction of sulfoximine-substituted trienes with the ruthenium catalyst 8. Two examples for the further synthetic elaboration of the sulfoximine-substituted carbocycles are provided. The selective cleavage of the tert-butyldimethylsilyl group of 12 in the presence of the triethylsilyl group afforded the allylic alcohol 18 which was oxidized to enone 19. A cross-coupling reaction of the sulfoximine-substituted carbocycle 9 with LiCuMe2 furnished the methyl-s...
TL;DR: Highly stereoselective methods have been developed that allow the generation of disaccharide mimetics with a high molecular diversity.
TL;DR: Formation of aryl ethers via a unique radical addition to the oxygen atom of the enone system is the main reaction when bulky secondary and tertiary alkyl radicals are used.
TL;DR: An enantioselective synthesis of the fully elaborated tricyclic decahydrofluorene core (ABC-ring system) of GKK1032s, novel antimicrobial and antitumor agents, has been accomplished for the first time by employing a highly diastereoselectives intramolecular Diels-Alder (IMDA) reaction.
Abstract: An enantioselective synthesis of the fully elaborated tricyclic decahydrofluorene core (ABC-ring system) of GKK1032s, novel antimicrobial and antitumor agents, has been accomplished for the first time by employing a highly diastereoselective intramolecular Diels−Alder (IMDA) reaction. The key substrate for the IMDA reaction was efficiently prepared through (i) an intermolecular Diels−Alder reaction between a siloxydiene and an optically active enone derived from d-mannitol to construct the appropriately functionalized C-ring and (ii) CuCl-promoted Stille coupling of an (E)-vinyl iodide and a vinylstannane to install the requisite triene side chain as the crucial steps.
TL;DR: Using the intermediates without N-protection as the substrates is essential because the corresponding N-Boc intermediates give poor diastereoselectivity.
Abstract: Condensation of a l-alanine derived δ-bromo-β-silyloxy-propylamine with 1,3-cyclohexadione followed by alkylative cyclization produces a bicyclic enone. Diastereoselective Pt/C-catalyzed hydrogenation of this enone in HOAc provides a 5-oxo-cis-fused decahydroquinoline. Wittig olefination of this decahydroquinoline and subsequent epimerization of the resulting 5-formyl intermediate gives rise to a 5-β-formyl decahydroquinoline exclusively. In a parallel procedure, Peterson reaction of this decahydroquinoline and subsequent hydrogenation of the generated 5-exo-olefin provides a decahydroquinoline with a 5-α-substituent predominantly. For these two diastereoselective processes, using the intermediates without N-protection as the substrates is essential because the corresponding N-Boc intermediates give poor diastereoselectivity. The intermediate with β-form side chain is further converted into lepadins A−C via carbon chain elongation, while the intermediate with α-form side chain is transformed into lepadins...
TL;DR: Analysis of cells following 24 h exposure to these drugs showed cell cycle arrest in the S and G2/M phase, in a dose‐dependent manner, and data indicate that the β′‐acyloxy‐α,β‐unsaturated ketones cause permanent damage to the cells and induce apoptosis.
Abstract: A series of β′-hydroxy-α,β-unsaturated ketones were prepared by means of an iron(III) catalyzed domino process. The in vitro antiproliferative activities were examined in the human solid tumor cell lines A2780, SW1573, and WiDr. The results showed that β′-hydroxy-α,β-unsaturated ketones were more potent than α,β-unsaturated ketones. The best activity profiles were obtained for the derivatives bearing cyclic or branched substituents on the side chains.
TL;DR: Beta-fluoroalkylated enones are efficient dienophiles in Diels-Alder cycloadditions to prepare various fluorinated cylic compounds, but the presence of the fluoroalksyl moiety modifies the reactivity and the selectivity of these cycloadDitions.
Abstract: β-Fluoroalkylated enones are efficient dienophiles in Diels−Alder cycloadditions to prepare various fluorinated cylic compounds. However, the presence of the fluoroalkyl moiety modifies the reactiv...
TL;DR: The cycloaddition between 1,3-cyclohexadiene and various enones and enals is accomplished at room temperature in yields ranging from 51 to 68% without the use of Lewis acids, high pressures, or microwave reactors.
Abstract: The cycloaddition between 1,3-cyclohexadiene and various enones and enals (methyl vinyl ketone, ethyl vinyl ketone, methacrolien) is accomplished at room temperature in yields ranging from 51 to 68% without the use of Lewis acids, high pressures, or microwave reactors. This normally sluggish cyclization is accomplished by precoordination of the diene to a π-basic molybdenum complex. The η2-bound metal is thought to promote a Michael reaction between the uncoordinated portion of the diene and the enone, and the resulting enolate then closes to form the cycloalkene product. The organic cycloadduct is removed by oxidation with air or with silver triflate in nearly quantitative yield. For more sterically hindered enones (e.g., mesityl oxide) and for methyl acrylate, the desired outcome requires the use of BF3·OEt2, and yields are significantly lower (15−35%)
TL;DR: The reaction of enone 1, bearing an internal nucleophilic moiety, i.e., furan or pyrrole (X = O, NR'), with isocyanides is presented and the formation of products resulting from the reaction of the zwitterionic intermediate 2 with a second equivalent of isOCyanide prior to cyclization to give 3.
TL;DR: The carbocyclic ring system of the aquariolide diterpenes has been synthesized by two routes involving a diastereoselective Pauson-Khand reaction and subsequent ring expansion.
TL;DR: In this paper, a two-step annulation strategy is proposed for synthesizing annulated versions of these heterocycles, which is based on the initial conjugate addition of a heteroaryl organometallic to an enone with trapping of the enolate as the silyl enolether.
TL;DR: A series of novel 3(5)-aryl/ferrocenyl-5(3)-phenothiazinylpyrazoles and pyrazolines were obtained by substituent-dependent regioselective condensation of the corresponding (E)-3-(2-alkyl-10H- phenothiazin-3-yl)-1-aryl/ ferrocene-2-en-1-one with hydrazine or methylhydrazine in acetic acid
Abstract: A series of novel 3(5)-aryl/ferrocenyl-5(3)-phenothiazinylpyrazoles and pyrazolines were obtained by substituent-dependent regioselective condensation of the corresponding (E)-3-(2-alkyl-10H-phenothiazin-3-yl)-1-aryl/ferrocenylprop-2-en-1-one with hydrazine or methylhydrazine in acetic acid. The different propensity of the primary formed β-hydrazino adducts to undergo competitive retro-Mannich reaction was interpreted in terms of tautomerisation equilibrium constants calculated by DFT using a solvent model. The regioselectivity of the cyclisation reactions with methylhydrazine and the substituent-dependent redox properties of pyrazolines were also rationalized by comparative DFT calculations performed for simplified model molecules. On the effect of ultrasound-promoted oxidation with copper(II)nitrate phenothiazine-containing pyrazolines, enones and oxo-compounds were selectively transformed into sulfoxides. Only one sulfoxide enone was partially converted into an oxirane derivative. The structure of the novel products was determined by IR and NMR spectroscopy including COSY, HSQC, HMBC and DNOE measurements.