- Studies Targeting Ryanodol Result in an Annulation Reaction for the Synthesis of a Variety of Fused Carbocycles
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An annulation reaction is described to access a range of polycyclic and highly oxygenated carbocycles. First developed in an approach to the synthesis of ryanodol, metallacycle-mediated annulative diketone-alkyne coupling defines a framework for realization of new retrosynthetic relationships for complex molecule synthesis. In addition to demonstrating this reaction in the context of forging distinct carbocyclic systems, including those featuring a seven-membered ring, the choice of quenching reagent leads to unique reaction outcomes.
- Karmakar, Rajdip,Rheingold, Arnold L.,Micalizio, Glenn C.
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Read Online
- Mechanistic study of samarium diiodide-HMPA initiated 5-exo-trig ketyl-olefin coupling: The role of HMPA in post-electron transfer steps
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The mechanistic importance of HMPA and proton donors (methanol, 2-methyl-2-propanol, and 2,2,2-trifluoroethanol) on SmI2-initiated 5-exo-trig ketyl-olefin cyclizations has been examined using stopped-flow spectrophotometric studies. In the pres
- Sadasivam, Dhandapani V.,Sudhadevi Antharjanam,Prasad, Edamana,Flowers II, Robert A.
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Read Online
- Tertiary Enamide-Triggered SEAr: Domino Allylation and Enamine-Type Addition
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Two unprecedented domino reactions are described, starting from ketospiro-enesulfonamides. By treatment with ZrCl4 and allylsilane, an intramolecular electrophilic aromatic substitution and subsequent allylation is observed. By treatment with TiCl4 and allylsilane, a double enamine-type reaction takes place, thus creating simultaneously four contiguous stereogenic centers diastereoselectively.
- Beltran, Frédéric,Miesch, Laurence
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supporting information
p. 1569 - 1573
(2019/03/12)
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- Mechanistic Study and Development of Catalytic Reactions of Sm(II)
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Samarium diiodide (SmI2) is one of the most widely used single-electron reductants available to organic chemists because it is effective in reducing and coupling a wide range of functional groups. Despite the broad utility and application of SmI2 in synthesis, the reagent is used in stoichiometric amounts and has a high molecular weight, resulting in a large amount of material being used for reactions requiring one or more equivalents of electrons. Although few approaches to develop catalytic reactions have been designed, they are not widely used or require specialized conditions. As a consequence, general solutions to develop catalytic reactions of Sm(II) remain elusive. Herein, we report mechanistic studies on catalytic reactions of Sm(II) employing a terminal magnesium reductant and trimethylsilyl chloride in concert with a noncoordinating proton donor source. Reactions using this approach permitted reductions with as little as 1 mol % Sm. Mechanistic studies provide strong evidence that during the reaction, SmI2 transforms into SmCl2, therefore broadening the scope of accessible reactions. Furthermore, this mechanistic approach enabled catalysis employing HMPA as a ligand, facilitating the development of catalytic Sm(II) 5-exo-trig ketyl olefin cyclization reactions. The initial work described herein will enable further development of both useful and user-friendly catalytic reactions, a long-standing, but elusive goal in Sm(II) chemistry.
- Maity, Sandeepan,Flowers, Robert A.
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supporting information
p. 3207 - 3216
(2019/02/19)
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- (Poly)cationic λ3-Iodane-Mediated Oxidative Ring Expansion of Secondary Alcohols
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Herein, a simplified approach to the synthesis of medium-ring ethers through the electrophilic activation of secondary alcohols with (poly)cationic λ3-iodanes (N-HVIs) is reported. Excellent levels of selectivity are achieved for C–O bond migration over established α-elimination pathways, enabled by the unique reactivity of a novel 2-OMe-pyridine-ligated N-HVI. The resulting hexafluoroisopropanol (HFIP) acetals are readily derivatized with a range of nucleophiles, providing a versatile functional handle for subsequent manipulations. The utility of this methodology for late-stage natural product derivatization was also demonstrated, providing a new tool for diversity-oriented synthesis and complexity-to-diversity (CTD) efforts. Preliminary mechanistic investigations reveal a strong effect of alcohol conformation on the reactive pathway, thus providing a predictive power in the application of this approach to complex molecule synthesis.
- Walters, Jennifer C.,Tierno, Anthony F.,Dubin, Aimee H.,Wengryniuk, Sarah E.
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supporting information
p. 1460 - 1464
(2018/04/06)
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- Synthesis of Highly Oxygenated Carbocycles by Stereoselective Coupling of Alkynes to 1,3- and 1,4-Dicarbonyl Systems
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Densely substituted and highly oxygenated carbocycles are challenging targets for synthesis. In particular, those possessing numerous contiguous, fully substituted carbon atoms (i.e., tertiary alcohols and quaternary centers) are often not accessible in a direct fashion, necessitating the strategic decoupling of ring-formation from the establishment of functionality about the system. Here, we describe an approach to the construction of highly oxygenated mono-, di-, and polycyclic carbocycles from the reaction of disubstituted alkynes with β- or γ-dicarbonyl systems. These processes embrace a variant of metallacycle-mediated annulation chemistry where initial alkyne-carbonyl coupling is followed by a second, now intramolecular, stereoselective C-C bond-forming event. In addition to revealing the basic reactivity pattern in intermolecular settings, we demonstrate that this class of reactivity is quite powerful in a fully intramolecular context and, when terminated by a stereoselective oxidation process, can be used to generate polycyclic systems containing a fully substituted and highly oxygenated five-membered ring.
- Kier, Matthew J.,Leon, Robert M.,O'Rourke, Natasha F.,Rheingold, Arnold L.,Micalizio, Glenn C.
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supporting information
p. 12374 - 12377
(2017/09/23)
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- Direct spirocyclization from keto-sulfonamides: An approach to azaspiro compounds
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Spontaneous spirocyclization of keto-sulfonamides via ynamides through a one-pot process is presented. Push-pull ynamides were obtained through Michael addition/elimination without Cu. The obtained azaspiro compounds are building blocks for indole alkaloids. Theoretical studies provide insights into the mechanism of the formal Conia-ene reaction.
- Beltran, Frédéric,Fabre, Indira,Ciofini, Ilaria,Miesch, Laurence
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supporting information
p. 5042 - 5045
(2017/11/06)
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- Cyclohexyl-4H,6H-5-oxa-2,3,10b-triaza-benzo[e]azulenes as V1a antagonists
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The present invention provides 4H,6H-5-oxa-2,3,10b-triaza-benzo[e]azulenes, which act as V1a receptor modulators, and in particular as V1a receptor antagonists, their manufacture, pharmaceutical compositions containing them and their use as medicaments. The active compounds of the present invention are useful as therapeutics acting peripherally and centrally in the conditions of dysmenorrhea, male or female sexual dysfunction, hypertension, chronic heart failure, inappropriate secretion of vasopressin, liver cirrhosis, nephrotic syndrome, anxiety, depressive disorders, obsessive compulsive disorder, autistic spectrum disorders, schizophrenia, and aggressive behavior.
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Paragraph 0174
(2014/08/19)
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- CYCLOHEXYL-4H,6H-5-OXA-2,3,10B-TRIAZA-BENZO[E]AZULENES AS V1A ANTAGONISTS
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The present invention provides 4H,6H-5-oxa-2,3,10b-triaza-benzo[e]azulenes, which act as V1a receptor modulators, and in particular as V1a receptor antagonists, their manufacture, pharmaceutical compositions containing them and their use as medicaments. The active compounds of the present invention are useful as therapeutics acting peripherally and centrally in the conditions of dysmenorrhea, male or female sexual dysfunction, hypertension, chronic heart failure, inappropriate secretion of vasopressin, liver cirrhosis, nephrotic syndrome, anxiety, depressive disorders, obsessive compulsive disorder, autistic spectrum disorders, schizophrenia, and aggressive behavior.
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Page/Page column 40
(2013/04/24)
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- Intramolecular reductive ketone-alkynoate coupling reaction promoted by (η2-propene)titanium
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Intramolecular reductive coupling of cycloalkanones tethered to alkynoates in the presence of (η2-propene)titanium was successfully performed to provide hydroxy-esters in a diastereoselective manner. Subsequent lactonization afforded angularly
- Schaefer, Christian,Miesch, Michel,Miesch, Laurence
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supporting information; scheme or table
p. 3253 - 3257
(2012/06/01)
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- Catalytic asymmetric hydrolysis: Asymmetric hydrolytic protonation of enol esters catalyzed by phase-transfer catalysts
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Like an enzyme: Asymmetric hydrolysis of enol esters is accomplished by chiral phase-transfer catalysts under biphasic base hydrolysis conditions. Stoichiometric reactions support the generation of a well-organized chiral ammonium hydroxide species (Q+OH-). Copyright
- Yamamoto, Eiji,Nagai, Ayano,Hamasaki, Akiyuki,Tokunaga, Makoto
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supporting information; experimental part
p. 7178 - 7182
(2011/08/03)
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- HETEROARYL-CYCLOHEXYL-TETRAAZABENZO[E]AZULENES
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The present invention provides heteroaryl-cyclohexyl-tetraazabenzo[e]azulenes of formula I wherein R1, R2 and R3 are as described herein. The compounds according to the invention act as V1a receptor modulators, and in particular as V1a receptor antagonists, their manufacture, pharmaceutical compositions containing them and their use as medicaments. The active compounds of the present invention are useful as therapeutics acting peripherally and centrally in the conditions of dysmenorrhea, male or female sexual dysfunction, hypertension, chronic heart failure, inappropriate secretion of vasopressin, liver cirrhosis, nephrotic syndrome, anxiety, depressive disorders, obsessive compulsive disorder, autistic spectrum disorders, schizophrenia, and aggressive behavior.
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Page/Page column 54
(2011/11/13)
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- HETEROARYL-CYCLOHEXYL-TETRAAZABENZO[E]AZULENES
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The present invention is concerned with heteroaryl-cyclohexyl-tetraazabenzo[e]azulenes of formula (I) wherein R1, R2 and R3 are as described herein. The compounds according to the invention act as Via receptor modulators, and in particular as Via receptor antagonists, their manufacture, pharmaceutical compositions containing them and their use as medicaments. The active compounds of the present invention are useful as therapeutics acting peripherally and centrally in the conditions of dysmenorrhea, male or female sexual dysfunction, hypertension, chronic heart failure, inappropriate secretion of vasopressin, liver cirrhosis, nephrotic syndrome, anxiety, depressive disorders, obsessive compulsive disorder, autistic spectrum disorders, schizophrenia, and aggressive behavior.
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Page/Page column 104; 105
(2011/12/02)
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- Gold-catalyzed 1,3-acyloxy migration/5-exo-dig cyclization/1,5-acyl migration of diynyl esters
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Working three shifts: Polyconjugated δ-diketones are formed stereoselectively in high yields by the gold-catalyzed rearrangement of 1,6-diyn-3-yl esters. This cascade involves a 1,3-sigmatropic acyloxy shift, a 5-exo-dig cyclization of the resulting allenyne, and an unprecedented 1,5-sigmatropic shift of an acyl fragment. The usefulness of the products was shown by an efficient acid-catalyzed transformation into a complex polycyclic framework. Copyright
- Lebuf, David,Simonneau, Antoine,Aubert, Corinne,Malacria, Max,Gandon, Vincent,Fensterbank, Louis
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supporting information; experimental part
p. 6868 - 6871
(2011/08/06)
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- Catalytic hydrophosphorylation of alkyl- and acylhydrazones
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N-Boc- and N-acylhydrazino phosphonates were obtained for the first time by hydrophos- phorylation of the appropriate hydrazones of aliphatic and aromatic aldehydes and heterocyclic and aliphatic ketones in the presence of [tetra(tert-butyl)phthalocyanine
- Matveeva,Podrugina,Kolesnikova,Prisyazhnoi,Karateev,Zefirov
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experimental part
p. 418 - 424
(2011/02/17)
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- Photoinduced atom-transfer cyclization of α-iodocycloalkanones bearing an allenyl side chain
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(Chemical Equation Presented) Irradiation of α-iodocycloalkanones bearing an allenyl side chain with a sunlamp effected atom-transfer cyclization to give cyclized products in good yield. A mechanism, involving radical atom-transfer cyclization accompanied
- Lin, Hsien-Hsun,Chang, Wen-Sheng,Luo, Shun-Yuan,Sha, Chin-Kang
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p. 3289 - 3292
(2007/10/03)
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- New cascade reactions starting from acetylenic ω-ketoesters: An easy access to electrophilic allenes and to 1,3-bridgehead ketones
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Acetylenic ω-ketoesters bearing a three carbon-carbon bond spacer reacted smoothly with tetra-n-butylammonium fluoride and with potassium tert-butoxide to afford either electrophilic allenes or 1,3-bridgehead ketones, the latter being potentially useful m
- Klein, Aurélie,Miesch, Michel
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p. 4483 - 4485
(2007/10/03)
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- Enzymatic resolution of bicyclo[n.1.0]alkan-1-ols derivatives: Preparation of optically active α-substituted α-methylcycloalkanones
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Optically active α-methyl α-substituted cycloalkanones are prepared by a chemoenzymatic sequence which involves a Lipozyme-catalyzed transesterification of 1-(chloroacetoxy)bicyclo[n.1.0]alkanes and ring opening of these cyclopropanol derivatives.
- Morisson,Barnier,Blanco
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p. 7749 - 7764
(2007/10/03)
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- Synthesis of Medium Ring Ethers. Part 2. Synthesis of the Fully Saturated Carbon Skeleton of Laurencia Non-terpenoid Ether Metabolites Containing Seven-, Eight- and Nine-membered Rings
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A general method for the construction of medium ring ethers is described in which a 2-substituted cycloalkanone was subjected to a Baeyer-Villiger ring expansion to the lactone, Tebbe methylenation of which afforded the enol ether which was subjected to a hydroboration-oxidation sequence to afford the 2,n-disubstituted oxacycle (n = ring size).Application of this procedure has led to efficient syntheses of the fully saturated skeletons corresponding to the naturally occurring Laurencia metabolites containing 2,n-dialkyl substituted seven- (isolaurepan), eight- (lauthisan and laurenan) and nine-membered (obtusan) ethers.
- Carling, Robert W.,Clark, J. Stephen,Holmes, Andrew B.
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- Formation of 1,2,3,4-Tetrahydro-2-pyridones by Aza-Annulation of Imines with Acrylate Derivatives
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The aza-annulation of imines with activated acrylate derivatives was studied as a means of preparing the corresponding 1,2,3,4-tetrahydro-2-pyridones.Through the use of reagents known to facilitate the formation of amide bonds from carboxylic acids, several methods of activating the acrylate species were compared.The acrylate derivatives studied were acryloyl chloride and acrylic anhydride as well as acrylic acid activated by reaction with EtO2CCl, (PhO)2P(O)N3, or MCPI.Optimum annulation was obtained with imines derived from cyclohexanone to produce octahydro-2-quinolone products.The N-isobutylimine prepared from cyclopentanone also produced selective ring annulation to efficiently produce the corresponding bicyclic product, but the reaction with the imine of n-butanal produced lower yields of cyclic product.Ring formation was relatively unaffected by substituents at the α-position of the acrylate derivative, demonstrated by the use of methacrylate, but β-substituents hindered the annulation process and, in turn, increased the amounts of byproduct resulting from only N-acylation of the imine.Increasing the steric bulk of the imine alkyl substituent produced the opposite effect; the relative amount of N-acylation compared to complete aza-annulation was diminished as the size of the substituent was increased.Mechanistic features of the reaction are discussed in terms of product distribution and competition experiments.
- Paulvannan, K.,Stille, John R.
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p. 5319 - 5328
(2007/10/02)
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- Synthesis of β-lactams via cycloaddition of hydrazones with phenoxyketene
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Phenoxyketene is capable of annelating the disubstituted hydrazones to afford stereoselectivity cis-monocyclic β-lactams with a 1-amino functionality. The ease of cycloaddition is governed by substitutents on the azomethine carbon as well as on the hydraz
- Sharma,Pandhi
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p. 2196 - 2200
(2007/10/02)
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- A Three-Step Pyridoannelation of Carbonyl Compounds
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The elaboration of a pyridine nucleus onto an α-methylene carbonyl compound can be accomplished through a three step reaction sequence based on the regiospecific alkylation of N,N-dimethylhydrazones with bromoethyl-1,3-dioxolane.Scope and limitations of the new method are considered.
- Marchetti, Mauro
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p. 1761 - 1765
(2007/10/02)
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- CO-OLIGOMERISATION DE BUTADIENE ET D'HETERODIENES AZOTES CATALYSEE PAR LE NICKEL CONTROLE DE LA SELECTIVITE
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Nickel (0) catalysed co-oligomerization of butadiene with heterodienes and hetero-olefins is described.It is shown how the selectivity of these reactions can be controlled by the position of the heteroatom in the heteropartner and also by the nature of th
- Brun, P.,Tenaglia, A,Waegell, B
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p. 5019 - 5030
(2007/10/02)
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- Novel hydrazinocarboxamide derivatives and preparation thereof
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α-Hydrazinocarboxamide and α-(α'-acylhydrazino)-carboxamide derivatives of formula I STR1 in which R1 and R2 each are lower alkyl or R1 and R2 together with the nitrogen atom to which they are joined form a pipe
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- Derivatives of imidazolidin-2-ones and -2-thiones
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There are disclosed herein derivatives of imidazolidin-2-ones and -2-thiones of the formula I SPC1 and their acid addition salts with pharmacologically acceptable acids, in which R1 is hydrogen or lower alkyl; R2 is lower alkyl, nitr
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