Showing papers on "Enone published in 1998"
TL;DR: In this paper, formal total synthesis of metacycloprodigiosin (2) and streptorubin B (3) is described, where the key step en route to their meta-bridged pyrrole core structures consists of a metathesis reaction of electron-deficient enynes catalyzed by either platinum halides, hard Lewis acids, or HBF4.
Abstract: Formal total syntheses of the antibiotics metacycloprodigiosin (2) and streptorubin B (3) are described, which are known to exhibit promising immunomodulating properties. The key step en route to their meta-bridged pyrrole core structures 5 and 7, respectively, consists of a metathesis reaction of electron-deficient enynes catalyzed by either platinum halides, hard Lewis acids, or HBF4. This transformation expands the pre-existing cycloalkene of the substrates by two C atoms, forges the bicyclic pyrrolophane structure of the targets, and simultaneously forms a bridgehead alkene function. The products of this skeletal rearrangement are converted into the targets by a sequence comprising (i) a stepwise reduction of their enone entity to the corresponding saturated alcohols and (ii) an aromatization of the N-tosylated dihydropyrroles 20 and 34 thus obtained via elimination of potassium sulfinate on exposure to KAPA (potassium 3-aminopropylamide). A careful analysis of the minor byproducts formed in the enyne...
300 citations
TL;DR: In this paper, the C-ring moiety was reduced under Birch conditions to the cyclohexadiene derivative, which was oxygenated by singlet oxygen from the convex β-face to give the C4β,C7β-diol stereoselectively.
Abstract: Enantioselective total synthesis of taxol has been accomplished. Coupling reaction of the optically pure A-ring hydroxy aldehyde with the aromatic C-ring fragment followed by Lewis acid mediated eight-membered B-ring cyclization gave the desired ABC endo-tricarbocycle. The C-ring moiety of this product was reduced under Birch conditions to the cyclohexadiene derivative, which was oxygenated by singlet oxygen from the convex β-face to give the C4β,C7β-diol stereoselectively. For introduction of the C19-methyl, the cyclopropyl ketone was prepared via cyclopropanation of the C-ring allylic alcohol or conjugate addition of a cyano group to the C-ring enone. Reductive cleavage of the cyclopropane ring followed by isomerization of the resulting enol to the corresponding ketone gave the crucial synthetic intermediate containing the C19-methyl group. Regioselective transformation of three hydroxyl groups of this intermediate, conversion of the C4-carbonyl group to the allyl chloride, and introduction of the C10-o...
214 citations
TL;DR: The first total synthesis of roseophilin was reported in this paper by means of a new palladium-catalyzed manifold for the formation of ansa-bridged pyrroles which proceeds via vinyl oxirane 8 and allyl lactone 11 as key intermediates.
Abstract: The first total synthesis of the antitumor agent roseophilin 1 is reported. Its intricate macrotricyclic core 2 is obtained by means of a new palladium-catalyzed manifold for the formation of ansa-bridged pyrroles which proceeds via vinyl oxirane 8 and allyl lactone 11 as key intermediates. After conversion of the latter into pyrrolophane 14, a base-induced elimination of the sulfone group followed by the Michael addition of a zincate onto the resulting enone 18 installs the isopropyl substituent in a stereoselective manner. The pyrrolylfuran side chain 3 of roseophilin is prepared from 4-methoxy-2(5H)-furanone (24) and methyl 4-chloropyrrole-2-carboxylate (26) as the starting materials. The appropriate building blocks 25a and 28 derived thereof are combined via a sequence comprising a directed metal−halogen exchange reaction, transmetalation of the resulting lithiopyrrole to the corresponding organozinc compound, a palladium-catalyzed cross coupling of the latter, and a subsequent acid-catalyzed closure ...
175 citations
TL;DR: A catalytic asymmetric synthesis of 11-deoxy-PGF1α has been achieved using a cascade Michael−aldol reaction as a key step, using an oxidative decarboxylation, an aldol reaction, and a Wharton reaction.
Abstract: A catalytic asymmetric synthesis of 11-deoxy-PGF1α has been achieved using a cascade Michael−aldol reaction as a key step. This cascade reaction was efficiently promoted by a catalytic use of AlLibis[(S)-binaphthoxide] complex (ALB) to give the three-component coupling product at room temperature in 92% ee and in 84% yield. The three-component coupling product was then converted to (+)-11-deoxy-PGF1α through several steps, including an oxidative decarboxylation, an aldol reaction, and a Wharton reaction. Moreover, the racemic enone, 20 was transformed into 21, the three-component coupling product, a potential intermediate for PGF1α, in 97% ee and in 75% yield through catalytic kinetic resolution.
76 citations
TL;DR: In this paper, the synthesis of pancratistatin from the prochiral ketone 1 using a chiral base to generate chiral enolate derivative is described. But this work is restricted to the case where the chirality was introduced by deprotonation with the lithium salt of (+)-bis(α-methylbenzyl)amine.
63 citations
TL;DR: In this article, a sulfur-based strategy for synthesis of otonecine was described, which includes the thio-Diels−Alder trapping of thioketone 8 by the Danishefsky diene followed by conversion into the enone 27 a...
Abstract: A sulfur-based strategy for synthesis of otonecine is described. Key steps include the thio-Diels−Alder trapping of thioketone 8 by the Danishefsky diene, followed by conversion into the enone 27 a...
58 citations
TL;DR: The [2 + 2 + 2] cycloaddition of diynes and enones occurred in the presence of both nickel and zinc together and had two interesting features.
Abstract: The [2 + 2 + 2] cycloaddition of diynes and enones occurred in the presence of both nickel and zinc together. This binary metal-mediated reaction had two interesting features: (1) a terminally unsubstituted diyne reacted with an enone to give an aromatic compound with the concomitant incorporation of two hydrogen atoms abstracted from an expected 1,3-diene product into another molecule of the starting enone and (2) a trimethylsilyl-substituted diyne reacted with an equimolar amount of enone to regioselectively afford a 1,3-diene, in which the trimethylsilyl group is adjacent to the carbonyl group.
57 citations
TL;DR: In this article, the relative configuration of the peroxide/α-methylacetate moiety of 6, 9, and 10, was directly determined from their NMR spectra.
Abstract: Natural free carboxylic acids from the hadromerid sponge Diacarnus levii (Kelly-Borges and Vacelet) were esterified to yield the new cyclic norditerpene peroxides ent-muqubilin benzyl ester (= (αR,3S,6R)-α,6-dimethyl-6-[(E)-4-methyl-6-(2,6,6-trimethyl-cyclohex-1-en-1-yl)hex-3-enyl]-1,2-dioxan-3-acetic acid benzyl ester; 6, diacarnoate B methyl ester(= (αS,3R,6R)-α,6-dimethyl-6-{2-(4aS,8aS)-3,4,4a,5,6,7,8,8a-octahydro-3-oxo-2,5,5,8a-tetramethylnaphthalen-1-yl)ethyl}-1,2-dioxan-3-acetic acid methyl ester; 9), and deoxydiacarnoate B benzyl ester (= (αS,3R,6R)-α,6-dimethyl-6-{2-[(4aS,8aS)-3,4,4a,5,6,7,8,8a-octahydro-2,5,5,8a-tetramethyl-1-naphthalenyl]ethyl}-1,2-dioxan-3-acetic acid benzyl ester; 10), which were isolated following extensive chromatography. The relative configuration of the peroxide/α-methylacetate moiety of 6, 9, and 10, was directly determined from their NMR spectra. The absolute configurations of the peroxide/α-methylacetate moiety was deduced from comparative 1H-NMR data of the (S)- and (R)-phenylglycine methyl ester derivatives 7 and 8 as well as 11/13 and 12/14, all obtained from a mixture of the precursors of 3, 6, and 10. The absolute configuration at the carbobicyclic moiety of enone 9 and of 10, is identical, as established by chemical interconversion, 9 and 10 belong to the normal labdane series according to empirical CD rules, applied either directly to 9 or to the parent (+)-sclareolide-derived enone 20. In contrast, molar rotation additivity rules suggest the ent-labdane configuration for 9 and 10. The epidioxides 1–3, 6, and 10 proved active in vitro against the malaria parasite Plasmodium falciparum; especially the previously isolated methyl 3-epinuapapuanoate (2) was active against a chloroquine-resistant strain, and this with a good security index.
47 citations
TL;DR: In this paper, the series of furyl enone esters, 4a−c, were synthesized from furan or furfural by straightforward routes, and their thermal intramolecular Diels−Alder reactions to give the tricyclic ketones 5a−C were...
Abstract: The series of furyl enone esters, 4a−c, were synthesized from furan or furfural by straightforward routes. Their thermal intramolecular Diels−Alder reactions to give the tricyclic ketones 5a−c were...
41 citations
TL;DR: An alpha-carbonyl radical cyclization approach toward synthesis of angular triquinanes is described and gas chromatographic analysis with a chiral column proved that 1 has high enantiomeric purity.
Abstract: An α-carbonyl radical cyclization approach toward synthesis of angular triquinanes is described. As a model study, conjugate addition of 4-(trimethylsilyl)-3-butynylmagnesium chloride to enone 7 followed by trapping of the enolate with chlorotrimethylsilane gave trimethysilyl enol ether 8. Iodination of 8 with a mixture of NaI and m-CPBA afforded iodo ketone 6. Radical cyclization of 6 effected by Bu3SnH and AIBN gave 5. Epoxidation of 5 with m-CPBA yielded epoxy ketone 9. Desilylation and rearrangement of 9 by formic acid gave aldehyde 4. Aldol condensation and dehydration furnished angular triquinane skeleton 3. Total synthesis of (−)-5-oxosilphiperfol-6-ene (1) was accomplished in 12 steps starting from keto ester 14 based on this route. Conjugate addition of 3-hexynylmagnesium bromide to chiral ester 13 followed by treatment with chlorotrimethylsilane gave intermediate 15. Iodination of 15 with a mixture of NaI and m-CPBA gave α-iodo ester 12. Intramolecular radical cyclization of 12 gave ester 11. Re...
39 citations
TL;DR: The total synthesis of (-)-ilimaquinone, a metabolite isolated from sea sponges, is described, where the key step of the synthesis is the attachment of the quinone moiety to the drimane skeleton.
Abstract: The total synthesis of (-)-ilimaquinone, a metabolite isolated from sea sponges, is described. The key step of the synthesis is the attachment of the quinone moiety to the drimane skeleton. Alkylation of enone 11 obtained in four steps from the readily available diketone 8, with tetramethoxybenzyl bromide 15 as the alkylating agent, led to addition product 16 in excellent yield. The presence of the tetramethoxybenzyl group induced stereoselective hydrogenation of the exo olefin 18, leading to the required isomer in a 9:1 ratio. Treatment of compound 21 with ceric ammonium nitrate (CAN) afforded formation of the quinone and deprotection of only one methyl ether in one step to furnish the desired ilimaquinone 1.
TL;DR: Taxol side chains 4, 7, 9 and 11, optically active protected N-benzoylphenylisoserines, were successfully synthesized by enantioselective aldol reaction from two achiral starting materials, benzaldehyde and an enol silyl ether derived from S-ethyl benzyloxyethanethioate as mentioned in this paper.
Abstract: Total asymmetric synthesis of Taxol was completed by dehydration condensation between a protected N-benzoylphenylisoserine 4 or 9 and 7-TES baccatin III which was prepared from 8-membered ring enone. Taxol side chains 4, 7, 9 and 11, optically active protected N-benzoylphenylisoserines, were successfully synthesized by enantioselective aldol reaction from two achiral starting materials, benzaldehyde and an enol silyl ether derived from S-ethyl benzyloxyethanethioate.
TL;DR: In this article, a diastereoselective synthesis of the octahydroquinoline enone precursor of pumiliotoxin C was achieved via tandem Mannich-Michael reaction on N-galactosyl imines.
TL;DR: The reaction of heterocyclic ketene animals with enones proceeds via an aza-ene addition followed by intramolecular cyclization to give imidazo[1,2-a]pyridine and imidaze[ 1,2,3-ij] [1,8]naphthyridine derivatives.
TL;DR: The aplyronine C1C11 subunit 4, containing 4 stereocentres and the (E,E)-diene system, was prepared in 7 steps from ethyl ketone (R)-8 using a boron-mediated anti aldol reaction and CBS enone reduction.
TL;DR: In this paper, polyleucine catalyzes the asymmetric epoxidation of enone in a non-aqueous medium to provide epoxy-ketones (2 ) and (3 ) (81 and 84% yields respectively; >98% ee ).
TL;DR: A formal synthesis of carbacylin was achieved by preparing a known advanced intermediate 15 via Zr-promoted enyne bicyclization-carbonylation, Pd-catalyzed α-alkenylation of bicyclic enones, and conjugate reduction as mentioned in this paper.
TL;DR: In this paper, a new protocol for the stereoselective conversion of glucose into an enantiomerically pure cyclopentane aldehyde was proposed, which achieved a 90% yield of enone.
Abstract: Methods for the annulation of carbohydrates have found extensive applications in organic synthesis. We report here a new protocol for the stereoselective conversion of glucose into an enantiomerically pure cyclopentane aldehyde 22. The readily available epoxide 15 was reacted with allyl Grignard to produce alcohol 16 in 86% yield. Swern oxidation followed by epimerization using triethylamine in N,N-dimethylformamide furnished the ketone 17 also in 86% yield. Regioselective deprotonation with lithium hexamethyldisilazane in THF was followed by methylation with methyl iodide and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidone as cosolvent to give 80% yield of ketone 18. Oxidation of ketone 18 by the Wacker procedure gave the 1,4-diketone 19 in 56% yield. Intramolecular aldol condensation occurred readily on treatment of diketone 19 with potassium tert-butoxide in toluene to furnish a 90% yield of enone 20. Treatment with N-bromosuccinimide produced the bromoester 21 in 72% yield, which was reduced to a mix...
TL;DR: In this article, the photodimerizable α,β-unsaturated ketone moiety of poly(meth)acrylates were characterized by ultraviolet, infrared, 1 H-nuclear magnetic resonance (NMR), and 13 C-NMR spectra, and gel permeation chromatography.
Abstract: Acrylate and methacrylate monomers with the photodimerizable α,β-unsaturated ketone moiety, such as 4-cinnamoylphenyl, 4-(4-methoxycinnamoyl)phenyl, 4-(4-nitrocinnamoyl)phenyl, or 4-(4-chlorocinnamoyl)phenyl, were prepared and homopolymerized using benzoyl peroxide as the initiator at 70°C in methyl ethyl ketone. The poly(meth)acrylates were characterized by ultraviolet, infrared, 1 H-nuclear magnetic resonance (NMR), and 13 C-NMR spectra, and gel permeation chromatography. Their thermal properties were studied by thermogravimetric analyses in air and nitrogen, and differential scanning calorimetry. The photocrosslinking properties of the polymers were investigated as thin films and in solution in the presence and absence of sensitizer.
TL;DR: The s-azido functionalization reaction provides a mechanistically different enone synthesis that involves treatment of 2 with fluoride anion to effect desilylation and concomitant s-elimination to give 3.
Abstract: The s-azido functionalization reaction provides a mechanistically different enone synthesis that involves treatment of 2 with fluoride anion to effect desilylation and concomitant s-elimination to give 3. Table 1 lists a number of examples of the direct conversion of a TIPS enol ether into the corresponding a,s-enone via a s-azido TIPS enol ether. The s-azido group can be ionized with Me3Al or Me2AlCl and the intermediate enonium ion trapped by a variety of nucleophiles such as an allylstannane, electron-rich aromatics, TMS enol ethers, Et2AlCN, Me2AlCCR, Me4AlLi, and vinylaluminum reagents to give the products listed in Table 2. The diastereoselectivity of the reaction of a 4-substituted enonium ion with indole shows an unusual increase of selectivity with increasing temperature. Reduction of the azide 2 provides access to s-amino TIPS enol ethers 5, which, for example, can be converted into a cinnamide derivative and cyclized via a putative “ene” process into a ?-lactam.
TL;DR: It is demonstrated that reaction design has a critical influence on the stereoselectivity and outcome of antibody-catalyzed aldol condensations.
Abstract: Enolate- and enamine-mediated versions of the aldol condensation can be catalyzed by antibodies. Antibody 78H6, an antibody against the quaternary ammonium hapten 1, catalyzes the enolate-mediated condensation of keto-aldehyde 2 to form aldol 3a and 3b and the subsequent β-elimination to form enone 4. Catalysis of both steps is promoted by a carboxylate side-chain on the antibody acting as a general base. Antibody 78H6 catalyzes this process 104 times more efficiently than acetate. Despite of this efficiency, stereochemical control occurs only in the elimination step by kinetic resolution. The stereochemistry of the carbon–carbon bond forming step from 2 to 3, which is not rate-limiting in this system, cannot be controlled by the antibody. Antibody 72D4, another antibody raised against hapten 1, can be combined with primary amine 5 to form an artificial aldolase catalyzing the aldol condensation of aldehydes such as 6 with acetone to form aldols 7a/b. Catalysis occurs via a covalent enamine mechanism, whereby condensation of the amine cofactor 5 with acetone to form the corresponding enamine 9, is promoted within the hydrophobic binding pocket of the antibodies by exclusion of water. In contrast to the enolate mediated reaction, the carbon–carbon bond formation is rate-limiting in the enamine mechanism, and the antibody shows a high level of stereoselectivity in this step. Stereoselectivity is a consequence of conformational control by a hydrogen bonding group on the antibody that activates the aldehyde carbonyl. This activation furthermore allows chemoselective catalysis of aldolization over β-elimination to occur. These experiments demonstrate that reaction design has a critical influence on the stereoselectivity and outcome of antibody-catalyzed aldol condensations.
TL;DR: In this article, the saturation of the double bond strictly depends from the substituent α to the carbonyl group and the saturated ketone is then oxidised in a Baeyer-Villiger type reaction.
Abstract: α,β-unsaturated aryl ketones, 1a–12 , have been submitted to the action of the fungus Beauveria bassiana (ATCC 7159) in growing conditions. The saturation of the double bond strictly depends from the substituent α to the carbonyl group. The saturated ketone is then oxidised in a Baeyer-Villiger type reaction. This new oxidative capacity of the fungus has been studied and the adaptability of the micro organism towards structural modifications has been investigated.
TL;DR: The first bis-protected enones with (4R, 5S)-stereochemistry were reported in this paper. But the enones were derived from D-(−)-quinic acid.
Abstract: The asymmetric synthesis of (4R,5S)- and (4S,5R)-4,5-bis(tert-butyldimethylsilyloxy)cyclohex-2-enone are described. Such bis-protected enones are useful intermediates in synthesis, and compounds with (4S,5R)-stereochemistry have previously been prepared from D-(–)-quinic acid. This paper reports the first synthesis of enones with (4R,5S)-stereochemistry. The route to the bis-protected enones involves chiral base-mediated rearrangement of meso-cyclohexene oxides to allylic alcohols followed by PDC oxidation. Two new chiral base reactions are described: rearrangement of a trans-epoxide generates an allylic alcohol of 76% ee (93% yield) whilst that of a cis-epoxide produces an allylic alcohol of 92% ee (38% yield); suggestions for the observed differences in yield and enantioselectivities are proposed.
TL;DR: In this paper, the sulfoxide esters 14 and 20d were successfully annulated with bicyclic enone 8 in the presence of tBuOLi to provide the pentacyclic ketones 9a and 21a respectively in good yields (≥70%).
TL;DR: The procedure of selective hydrogenation with gaseous tritium of 16α,17α-cyclohex-3'-en-pregna-1,4-dien-3,20-dione (StO) has been elaborated in this article.
Abstract: The procedure of selective hydrogenation with gaseous tritium of 16α,17α-cyclohex-3'-en-pregna-1,4-dien-3,20-dione (StO) has been elaborated, and isotopically labelled 16a,17a-cyclohexanopregna-1,4-dien-3,20-dione (St1), 16α, 1 7α-cyclohex-3'-en-pregn-4-en-3,20-dione (St2), 16α,17α-cyclohexanopregn-4-en-3,20-dione (St3) with molar radioactivity of 41, 44, 85 Cilmmol, respectively, obtained. By hydrogenation with gaseous hydrogen, tritium labelled (St3) was converted to 16α, 17α-cyclonexano-5α-pregnan-3,20-dion (5α-St4) and 16α,17α-cyclohexano-5β-pregnan-3,20-dione (5β-St4).
TL;DR: In this article, the reaction of (S,E)-3-(p-tolylsulfinyl)pent-3-en-2-one with an isopropyl radical was shown to give an unexpected α-(arylsulfanyl) enone which is formed through a radical addition and subsequent Pummerer-type rearrangement.
Abstract: The reaction of (S,E)-3-(p-tolylsulfinyl)pent-3-en-2-one with an isopropyl radical, generated from isopropyl iodide and triethylborane, gives the non-stereoselective addition product and an unexpected α-(arylsulfanyl) enone which is formed through a radical addition and subsequent Pummerer-type rearrangement. The formation of the α-(arylsulfanyl) enone depends upon the additives used as well as the aryl group on the sulfur.
TL;DR: The first enantiospecific total synthesis of (+)-2-pupukeanone and 5-epi-2pukeanones has been achieved starting from (R)-carvone, employing a radical cyclisation reaction based approach.
Abstract: The first enantiospecific total synthesis of (+)-2-pupukeanone and 5-epi-2-pupukeanone has been achieved starting from (R)-carvone, employing a radical cyclisation reaction based approach. (R)-Carvone has been transformed into the bicyclo[2.2.2]octenone 12 via kinetic alkylation, bromination of the isopropenyl moiety and intramolecular alkylation, which on further alkylation with prenyl bromide leads to bicyclo[2.2.2]octenone 16, The 5-exo-trig radical cyclisation of the bromohydrin 17, obtained from 16, furnishes an epimeric mixture of the isotwistanes 19 and 20 along with a minor amount of the rearranged product 21. Ozonolytic cleavage of the exomethylene moiety, dehydration of the tertiary alcohol and regioselective Wolff-Kishner reduction transforms the isotwistanes 19 and 20 into the enone 24, Alternatively, kinetic alkylation of the bicyclo[2.2.2]octenone 12 with 1,4-dibromo-2-methylbut-2-ene followed by 5-exo-trig allyl radical cyclisation of 35 and selective functional group transformations generates the isotwistane 23 and a minor amount of the rearranged product 29. Finally, catalytic hydrogenation transforms the enone 24 into (+)-2-pupukeanone 5 and its C-5 epimer 6.
TL;DR: In this article, the structural identities and stereochemistry of cyclized products have been determined by X-ray diffraction, and the diastereoselectivity in the formation of the 7-membered ring bislactam product was found to be 91.6% de.
Abstract: Organoselenium-induced cyclofunctionalization of the (S)-N-(α,β-unsaturated) acylprolinamides 1, 7 and 14 has been found to produce the 7-membered bislactam products 2 and 15, or the 6-membered phenylselenolactam products 8 and 9 depending on the substitution pattern of the enone moiety of the starting material. The structural identities and stereochemistry of the cyclized products have been determined by X-ray diffraction, and the diastereoselectivity in the formation of the 7-membered ring bislactam product was found to be 91.6% de. The mechanism of the cyclolactamization is discussed.
TL;DR: The mechanism and level of regioselectivity depend on both the substitution pattern of the substrates and the reaction conditions as mentioned in this paper, and the least bulky substituent is attached at the β position of the enone, usually higher than that from equivalent β-diketones.
Abstract: β-Aminoenones react with monoalkyl hydrazines to give regioselectively 1,3,5-trisubstituted pyrazoles. The mechanism and level of regioselectivity depend on both the substitution pattern of the substrates and the reaction conditions. When the least bulky substituent is attached at the β-position of the enone, a high regioselectivity is obtained, usually higher than that from equivalent β-diketones. If the β-substituent is the bulkiest group, the regioselectivity decreases. Nevertheless, in the conditions reported in this paper, it is possible to prepare pyrazoles not obtainable from β-diketones.