- Acid-Catalyzed Hydration of α-Cyano and α-Trifluoromethyl Vinyl Ethers. Additivity of Strongly Activating and Strongly Deactivating Substituent Effects
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The reactivities of 1-cyano-1-ethoxyethylene (1) and 1-(trifluoromethyl)-1-ethoxypentene (2) in aqueous H2SO4 and D2SO4 have been measured.The kinetics and products establish the mechanism of these reactions as rate-limiting protonation on the double bond.The observed rates are predicted with surprising accuracy by the previously introduced correlation logkH+ = -10.5Σp+ - 8.92.
- Allen, Annette D.,Shahidi,, Fereidoon,Tidwell, Thomas T.
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- Stereocontrolled entry to β-C-glycosides and bis-C,C-glycosides from C-glycals: preparation of a highly functionalized triene from D-mannose
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The C(3) hydroxyl group of C-glycals can be readily converted into mixed halo-acetals of 2-bromo-acetaldehyde. Radical reaction of the latter mediated by tri-n-butyltin hydride, with or without a radical acceptor, led diastereoselectively to either P-C-glycosides or bis-C,C-glycosides, respectively. The latter have been transformed into a highly functionalized triene, which is a potential precursor in a proposed synthesis of labdane type diterpenes from D-mannose.
- Gornez, Ana M.,Casillas, Marta,Valverde, Serafin,Lopez, J. Cristobal
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- TOTAL SYNTHESIS OF (-)-ISOAVENACIOLIDE AND (-)-ETHISOLIDE
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Natural isoavenaciolide and ethisolide were obtained from two bis-butyrolactone intermediates derived from a common bicyclic ester 8, prepared from D-ribose.
- Wee, Andrew G. H.
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- Chiral β-lithio enol ethers: Synthesis and properties
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Chiral lithio enol ethers 1 obtained from corresponding Z-bromo enol ethers react with alkyliodides, acylchlorides, leading to new chiral enol ethers of controlled configuration 5-8.
- Godebout, Virginie,Lecomte, Sandrine,Levasseur, Frederic,Duhamel, Lucette
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- Copper(I)-Catalyzed Stereo- and Chemoselective Borylative Radical Cyclization of Alkyl Halides Bearing an Alkene Moiety
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The stereoselective borylative radical cyclization of alkyl halides containing an alkene moiety was developed using a copper(I)/diboron catalyst system. The optimized reaction conditions allowed us to control the chemoselectivity between the allylic substitution and the borylative radical cyclization. The borylation products were subsequently converted to highly functionalized organic compounds by derivatization of the newly formed C-B bond. This borylative radical cyclization offers a novel methodology for the stereoselective synthesis of various heterocyclic compounds.
- Iwamoto, Hiroaki,Akiyama, Sota,Hayama, Keiichi,Ito, Hajime
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supporting information
p. 2614 - 2617
(2017/05/24)
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- Total synthesis of (±)-sacidumlignans D and A through Ueno-Stork radical cyclization reaction
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Efficient synthesis of (±)-sacidumlignan D (4) has been successfully achieved employing Ueno-Stork radical cyclization of α-bromo acetal 21 as a key step. Two synthetic approaches for the symmetrical diaryl ketone 19 have been discussed in detail. Notably, sacidumlignan A (1) can be also efficiently synthesized in only 7 steps with 25% overall yield, where acid triggered tandem reaction starting from analogous Ueno-Stork cyclization product 27 played an important role. Moreover, potentially biomimetic conversion from (±)-sacidumlignan D (4) to sacidumlignan A (1) could be realized. The Royal Society of Chemistry 2013.
- Zhang, Jian-Jian,Yan, Chang-Song,Peng, Yu,Luo, Zhen-Biao,Xu, Xiao-Bo,Wang, Ya-Wen
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p. 2498 - 2513
(2013/06/26)
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- Concise synthesis of the Hasubanan Alkaloid (±)-cepharatine A using a Suzuki coupling reaction to effect o,p -phenolic coupling
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Suzuki coupling of 10 and 11 resulted in 9, which was O-alkylated to provide 12. Treatment of 12 with CsF in DMF resulted in the formation of the completed core structure 13 in a single step. Reductive amination of 13 completed the synthesis of (±)-cepharatine A, 4.
- Magnus, Philip,Seipp, Charles
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supporting information
p. 4870 - 4871
(2013/10/08)
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- Synthesis of the gymnodimine tetrahydrofuran core through a Ueno-Stork radical cyclization
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A straightforward access to the C10-C20 skeleton of gymnodimine, incorporating a tetrahydrofuran fragment, is described. The elaboration of the THF moiety is based on a stereocontrolled Ueno-Stork cyclization. A Lewis-acid mediated allylation of the resulting acetal at C13 and a Horner-Wadsworth-Emmons olefination on the ketone at C17 complete the synthesis.
- Toumieux, Sylvestre,Beniazza, Redouane,Desvergnes, Valerie,Araoz, Romulo,Molgo, Jordi,Landais, Yannick
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supporting information; experimental part
p. 3726 - 3732
(2011/06/27)
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- An efficient synthesis of a potential (-)-reserpine intermediate from (-)-shikimic acid of the chiral pool
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A highly stereoselective route to the polysubstituted chiral octahydrobenzofuran 12, a potential synthon for the E-ring core in the (-)-reserpine synthesis, is described. The α-bromo acetal 11 was obtained from inexpensive (-)-shikimic acid (3) through a series of highly stereoselective chemical reactions (Scheme). Et3B/Bu 3SnH-Mediated intramolecular radical cyclization of 11 led to compound 12 with the required configuration.
- Huang, Jian,Chen, Fen-Er
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p. 1366 - 1372
(2008/02/07)
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- Total synthesis and bioactivity of an unnatural enantiomer of merrilactone A: Development of an enantioselective desymmetrization strategy
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(Chemical Equation Presented) (-)-Merrilactone A [(-)-1], isolated from Illicium merrillianum in 2000, possesses neurite outgrowth activity in cultures of fetal rat cortical neurons, and, therefore, is expected to show therapeutic potential for the treatment of neurodegeneration associated with Alzheimer's and Parkinson's diseases. A part from its biological aspects, the caged pentacyclic skeleton of 1 poses interesting synthetic challenges. Here, we report the total synthesis of the unnatural enantiomer of merrilactone A [(+)-1], based on a novel desymmetrization strategy. The chiral lithium amide 16g promoted an enantioselective transannular aldol reaction of eight-membered meso-diketone 3d, establishing the absolute stereochemistries of four chiral centers of the cis-bicyclo[3.3.0]octane framework of 1 in a single step. The obtained compound 4d served as a platform for the subsequent functional group manipulations necessary for the construction of (+)-1. Surprisingly, both the natural and unnatural enantiomers of synthetic merrilactone A equally promoted neurite outgrowth in primary neuronal cultures.
- Inoue, Masayuki,Lee, Nayoung,Kasuya, Satoshi,Sato, Takaaki,Hirama, Masahiro,Moriyama, Miyako,Fukuyama, Yoshiyasu
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p. 3065 - 3075
(2008/02/07)
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- Asymmetric total synthesis of (-)-merrilactone A: Use of a bulky protecting group as long-range stereocontrolling element
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(Chemical Equation Presented) Designer elegance: The transannular aldol reaction of a cyclooctene diketone is the key step in this total synthesis of the natural enantiomer of merrilactone A (see scheme). The configuration of the two stereocenters generated in the formation of the central bicyclo[3.3.0]octane framework of the natural product was established using a specially designed bulky protecting group.
- Inoue, Masayuki,Sato, Takaaki,Hirama, Masahiro
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p. 4843 - 4848
(2007/10/03)
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- Synthesis of optically pure (+)-puraquinonic acid and assignment of absolute configuration to natural (-)-puraquinonic acid. Use of radical cyclization for asymmetric generation of a quaternary center
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An asymmetric aldol reaction between aldehyde 31 and imide 32, followed at a later stage by ring-closing metathesis (38 → 40), are key reactions used to make optically pure allylic alcohol 40. Radical cyclization of the derived Stork bromo acetals gives lactol ethers 43, which were degraded to generate a quaternary center carrying a methoxycarboxyl group (44 → 47). Compound 47 was converted into (+)-puraquinonic acid; and comparison with a natural sample established that the configuration of the natural compound is 2R (1).
- Clive, Derrick L. J.,Yu, Maolin,Sannigrahi, Mousumi
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p. 4116 - 4125
(2007/10/03)
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- Total synthesis of merrilactone A
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Merrilactone A (1) has been shown to possess neurotrophic activity and thus is expected to hold therapeutic potential in the treatment of neurodegeneration diseases. In this paper, we report the total synthesis of (±)-1, employing, as key steps, a novel desymmetrization protocol of meso-diketone to construct the core cis-bicyclo[3.3.0]octyl system of 1 (3 → 2) and a radical cyclization to install the highly congested C9-quaternary carbon (16 → 17). Copyright
- Inoue, Masayuki,Sato, Takaaki,Hirama, Masahiro
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p. 10772 - 10773
(2007/10/03)
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- Approach towards an EPC synthesis of nodusmicin. Part 5: Stereoselective introduction of a side chain at the cis-decalin part of nodusmicin
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The introduction of the side chain at C-4 of cis-decalin 2 and closure of the oxygen bridge are reported. Partial dehydrogenation of 2 was followed by oxymercuration and halogen-mercury exchange. Intermolecular radical addition to acrylic ester occurred from the convex face of the tricyclic compounds 7a and 7b. Consecutive epimerization failed. Therefore, two methods using intramolecular attachment of the side chain were developed. Formation of the β-iodoacetal of the cyclic allylic alcohol 21 permitted intramolecular radical addition generating the desired configuration at C-4 of the decalin. Likewise formation of the β bromoacetal with the exo-cyclic hydroxy group of tricycle 12 led via SN2-reaction to tetrahydropyrans with the desired configuration at C-4. The oxygen bridge was introduced by dehydration of the exo-cyclic alcohol and consecutive oxymercuration. Mercury-oxygen exchange completed the reaction sequence.
- G?ssinger, Edda,Schwartz, Alexander,Sereinig, Natascha
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p. 3045 - 3061
(2007/10/03)
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- Serial radical reactions of glycals: Ready routes to highly functionalized C-glycosyl derivatives
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The C3-OH of partially protected glycals can be readily converted into mixed acetals of 2-bromoacetaldehyde or into silylmethylene bromides. Reaction of these derivatives with tri-n-butyltin hydride gives a radical that cyclizes efficiently to generate a stabilized radical at C1. The latter can be trapped very efficiently with acrylonitrile, tert-butyl isocyanide, allyltri-n-butyltin, tributyltin acrylates, or a complex pyranoside enone to afford C-glycosides in which a 1,2 disubstitution has taken place. The stereochemistry of the resulting 1,2 disubstituted product is dependent, at C-2, on the stereochemistry of the C3-OH and at the anomeric center (C-1) upon the interplay of (a) steric effects and (b) the electronic bias of the radical anomeric effect.
- Cristobal Lopez,Gomez,Fraser-Reid
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p. 3871 - 3878
(2007/10/02)
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- Inversion of an Asymmetric Center in Carbocyclic Inhibitors of 3-Dehydroquinate Synthase: Examining and Exploiting the Mechanism for syn-Elimination during Substrate Turnover
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Conversion of 3-deoxy-D-arabino-heptulosonic acid 7-phosphate (DAHP) into 3-dehydroquinate (DHQ) by the enzyme DHQ synthase has been proposed to proceed through a step where the phosphate monoester of a reactive intermediate mediates its own elimination.This hypothesis was tested by challenging DHQ synthase with a series of carbocyclic substrate analogues possessing an inverted methine carbon relative to the same asymmetric center in substrate DAHP which loses a proton during elimination of inorganic phosphate.Despite the stereochemical alternation, epicarbocyclic substrate analogues 5--5-deoxyquinate, 5-(phosphonomethyl)-5-deoxyquinate, 5-(phosphonoethyl)-5-deoxyquinate, and 3-(phosphonooxy)quinate inhibited DHQ synthase with respective inhibition constants (Ki) of 30 nM, 55 nM, 30 μM, and 53 μM.These inhibitors were synthesized from quinic acid and with the exception of 3-(phosphonooxy)quinate, were assembled via a strategy employing intramolecular, radical cyclization to establish the stereocenter where the (phosphonooxy)methyl, phosphonomethyl, and phosphonoethyl moieties were attached to the carbocyclic ring.The observed diastereomeric promiscuity in the binding of epicarbocyclic substrate analogues by DHQ synthase is consistent with the hypothesized nonenzymic syn-elimination of inorganic phosphate during substrate turnover.
- Montchamp, Jean-Luc,Peng, Jirong,Frost, J. W.
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p. 6999 - 7007
(2007/10/02)
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- RADICAL CYCLIZATION ONTO 2(5H)-FURANONE AND MALEATE ELECTROPHORES. AN APPROACH TO THE SPIRO- AND LINEAR-FUSED γ-LACTONE RING SYSTEMS FOUND IN THE GINKGOLIDES
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Intramolecular radical cyclizations involving α-acetal methyl centres, and 2(5H)-furanone and maleate electrophores, allow the facile synthesis of spiro- and linear-fused γ-lactone ring systems e.g. (5), (6), (7) and (8) present in the 'ginkgolides' viz (1) and (2) produced by the ginko tree Ginkgo biloba.
- Harrison, Timothy,Myers, Peter L.,Pattenden, Gerald
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p. 5247 - 5262
(2007/10/02)
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- A RADICAL CYCLISATION ROUTE TO (+/-)-ANDIROLACTONE, A SPIRO-γ-BUTYROLACTONE
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Synthesis of Andirolactone (1), starting from 4-methyl cyclohex-3-en-1-one (5), via the radical cyclisation of the bromoacetal (7), is described.
- Srikrishna, A.,Veera Raghava Sharma, G.
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p. 6487 - 6488
(2007/10/02)
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- Intramolecular Free Radical Cyclisations onto Enol Ethers. A General Synthesis of α-Alkyl-β-oxy- and α-Methylene-β-oxy-γ-butyrolactones
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Radical cyclisation of the enol ether bromoacetals (26), (28a-c), (29), and (37) in the presence of tributylstannane, produces precursors to the β-oxy-γ-butyrolactones (33), (34a-c), (35), and the α-methylene-β-oxy-γ-butyrolactone (39) in high overall yields.By contrast, treatment of (26) and (28a-b) with the cobalt(I) reagent derived from bis(dimethylglyoximato)(pyridine)cobalt(III) chloride (40), followed by oxidation of the intermediates (43) leads to the corresponding unsaturated β-oxy-γ-butyrolactones (42).
- Begley, Michael J.,Landlow, Mark,Pattenden, Gerald
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p. 1095 - 1106
(2007/10/02)
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- Dehydrobromination of 1,2-Dibromoethoxyethane Using Various Amine Bases
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1,2-Dibromoethoxyethane was treated with a number of basic reagents, mainly tertiary amines, to accomplish dehydrobromination to 1-bromo-2-ethoxyethene, a precursor to an acetaldehyde carbanion equivalent.The yield of this vinyl bromide and the other common byproducts of reaction varied markedly depending on the base and reaction conditions employed.Direct distillation of the product under reduced pressure from a tertiary amine solution was the method of choice, showing little if any effect of temperature and giving reproducible results.Following this procedure, N,N-dimethyldodecylamine was the preffered base for this reaction.This paper presents results of the dehydrobromination reaction using more than 30 different bases and conditions
- Stalick, Wayne M.,Khorrami, Ali,Hatton, Kimi S.
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p. 3577 - 3581
(2007/10/02)
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- THERMOLYSIS OF THE CHLOROFLUOROCARBENE 1-ETHOXY-1-PHENOXYETHYLENE ADDUCT TO PHENYL 2-FLUOROACRYLATE
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The preparation of 1-ethoxy-1-phenoxyethylene 1 is described.Its condensation with chlorofluorocarbene gives 2,2-chlorofluorocyclopropanone acetal 2, thermolysis of which leads to phenyl 2-fluoroacrylate 3.
- Nguyen, T.,Molines, H.,Wakselman, C.
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p. 925 - 930
(2007/10/02)
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- INTRAMOLECULAR FREE RADICAL CYCLISATIONS ONTO VINYL ETHERS. A METHOD FOR THE SYNTHESIS OF β-OXY-γ-BUTYROLACTONES
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Radical cyclisation of the vinyl ether bromides (2) and (7) in the presence of tri-n-butylstannane produces precursors to the β-oxy-γ-butyrolactones (6) and (9) in high yields (>80percent).By contrast, treatment of (2) and (7) with bis-(dimethylglyoximato)(pyridine)cobalt(I) chloride followed by oxidation of the intermediates (5) and (11) led to the corresponding unsaturated β-oxy-γ-butyrolactones (4) and (12) respectively.
- Ladlow, Mark,Pattenden, Gerald
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p. 4317 - 4320
(2007/10/02)
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- 15-Deoxy-16-hydroxy-16-(1'fluorovinyl) prostaglandins and derivatives
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15-Deoxy-16-(halovinyl)-16-hydroxy prostaglandins have been prepared.
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- 1-Hydroxymethyl-1-oxo-prostane-derivatives of the E, A and F-series
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The invention disclosed herein relates to pharmacologically active prostaglandin derivatives of the E, F, or A series having on the terminal methylene carbon of the alpha chain a substituent selected from the group consisting of: STR1 wherein R is an alkyl group and R15 is C1 -C4 alkyl, di-C1 -C4 -alkylamino, C1 -C4 alkoxy, and phenyl or phenyl substituted with one or more substituents from the group consisting of C1 -C4, OR, SR, F, or Cl wherein R is as previously defined.
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- 1-Substituted-1-oxo-prostane-derivatives of the E, A and F series
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The invention disclosed herein relates to pharmacologically active prostaglandin derivatives of the E, F, or A series having on the terminal methylene carbon of the alpha chain, a substituent selected from the group consisting of: STR1 wherein R is C1 to C6 alkyl, and phenyl or phenyl substituted with one or more substituents selected from the group consisting of C1 -C4 alkyl, OR16, SR16, F, or Cl, and R16 is C1 to C6 alkyl.
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- 15-Deoxy-16-hydroxy-16-(1'fluorovinyl) prostaglandins and derivatives
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15-Deoxy-16-hydroxy-16-(1 halovinyl) prostaglandins have been prepared.
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- Terpenes and Terpene Derivatives, XI. - Synthesis and Reductions of β-Santalenone hept-2-yl)-3-penten-2-one>
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Starting from cyclopentadiene (2) and 2-butynoic acid (3), and via the acids 5 and 7, the allyl alcohol 9 has been prepared. 9 reacts with the dienol ether 10 to give β-santalenone 11.Reduction of 11 with LiAlH4/AlCl3 yields, depending on the reaction temperature various amounts of hydrocarbons 25, 26, and β-santalenone (1), of the ketone 27 and of the alcohol 28.With NaBH4 the alcohols 28 and 29 have been obtained.
- Simmross, Frank-Michael,Weyerstahl, Peter
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p. 1089 - 1099
(2007/10/02)
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