- An Organocatalytic Access to Spiro[45]decanes and Spiro[4.6]undecanes Containing Aminolactones and 3-Aminopyrrolidines
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The organocatalyzed Mannich coupling of cyclic carboxaldehydes allowed the concise and simple preparation of spirocyclic aminolactones. Their conversion into pharmaceutically relevant spiro[4.5]cyclic and spiro[4.6]cyclic 3-aminopyrrolidines is also described.
- Cormier, Morgan,Chardon, Aurélien,Blanchet, Jér?me,Rouden, Jacques,Maddaluno, Jacques,De Paolis, Micha?l
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Read Online
- Methylene C(sp3)-H β,β′-Diarylation of Cyclohexanecarbaldehydes Promoted by a Transient Directing Group and Pyridone Ligand
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A hindered β-amino amide transient directing group effects di-trans-arylation of cyclohexanecarbaldehydes. The amide N-substituents are shown to affect yield and can enhance the rate of arylation compared with the α-amino acid. Addition of a pyridone ligand further enhanced reactivity. The reaction is successful for a range of aryl iodides, and various substituted cyclohexane carboxaldehydes, providing functionalized products from simple feedstocks. A mechanism is proposed evoking a transient enamine.
- Bull, James A.,St John-Campbell, Sahra,White, Andrew J. P.
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supporting information
(2020/03/10)
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- BIARYL PYRAZOLES AS NRF2 REGULATORS
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The present invention relates to biaryl pyrazole compounds, methods of making them, pharmaceutical compositions containing them and their use as NRF2 regulators.
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Page/Page column 539
(2017/08/01)
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- AMINE DERIVATIVE COMPOUNDS FOR TREATING OPHTHALMIC DISEASES AND DISORDERS
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Provided are amine derivative compounds, pharmaceutical compositions thereof, and methods of treating ophthalmic diseases and disorders, such as age-related macular degeneration and Stargardt's Disease, using said compounds and compositions.
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Paragraph 1895; 1897
(2016/08/07)
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- An Effective Pd-Catalyzed Regioselective Hydroformylation of Olefins with Formic Acid
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An effective palladium-catalyzed regioselective hydroformylation of olefins with formic acid is described. The ligand plays a crucial role in directing the reaction pathway. Linear aldehydes can be obtained in up to 93% yield with >20:1 regioselectivity using 1,3-bis(diphenylphosphino)propane (dppp) as the ligand. The reaction process is operationally simple and requires no syngas.
- Ren, Wenlong,Chang, Wenju,Dai, Jie,Shi, Yuan,Li, Jingfu,Shi, Yian
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supporting information
p. 14864 - 14867
(2016/11/29)
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- Enantioselective synthesis of gabapentin analogues via organocatalytic asymmetric Michael addition of α-branched aldehydes to β-nitroacrylates
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Michael addition reaction of α-branched aldehydes to β-nitroacrylates was successfully carried out by using a mixed catalyst consisting of a primary amino acid, l-phenylalanine, and its lithium salt to give β-formyl-β′-nitroesters having a quaternary carbon centre in good yields (up to 85%) with high enantioselectivity (up to 98% ee). By using benzyl β-nitroacrylates as Michael acceptors, the obtained β-formyl-β′-nitroesters were converted into various 4,4-disubstituted pyrrolidine-3-carboxylic acids including analogues of gabapentin (Neurotin) in one step from the Michael adducts in high yields. The Royal Society of Chemistry 2012.
- Yoshida, Masanori,Masaki, Erika,Ikehara, Hiroto,Hara, Shoji
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supporting information; experimental part
p. 5289 - 5297
(2012/08/08)
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- HERBICIDALLY ACTIVE 2-(SUBSTITUTED-PHENYL)-CYCLOPENTANE-1,3-DIONE DERIVATIVES
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Compounds of formula (I) are suitable for use as herbicides: wherein R is methyl, ethyl, vinyl, ethynyl or cyclopropyl, R1 is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C3-C7cycloalkyl, C1-C6alkoxy, C1-C6haloalkoxy, vinyl, propenyl, ethynyl, propynyl, halogen, or optionally substituted phenyl, R2 is methyl, ethyl, vinyl, ethynyl or methoxy, R3 and R4 are hydrogen or together form a double bond, A is C3-C7cycloalkyl which is unsubstituted or substituted once or twice by C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy, C1-C6alkylcarbonyloxy, C2-C6alkenyl, =0 or =N-R10, or A is cyclohexyl substituted once, at the 4-position, by one (C3-C6cycloalkyl)methoxy, C3-C6cycloalkyloxy, C2-C5alkenyl-CH2-oxy, or benzyloxy substituent, or A is decahydro-1-naphthyl or decahydro-2-naphthyl, or A is optionally substituted phenyl, and G is hydrogen or an agriculturally acceptable metal, sulfonium, ammonium or a latentiating group.
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Page/Page column 70-71
(2011/02/24)
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- Tandem metal and organocatalysis in sequential hydroformylation and enantioselective mannich reactions
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Metal-catalysed hydroformylation is successfully combined with an organocatalysed stereoselective Mannich reaction in a tandem reaction sequence. This novel type of "tandem catalysis" allows access to complex molecular systems with high levels of enantioselectivity, using simple starting materials and an amino acid as the chiral catalyst.
- Chercheja, Serghei,Rothenbuecher, Thomas,Eilbracht, Peter
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experimental part
p. 339 - 344
(2009/11/30)
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- ALKYNYL PHENYL DERIVATIVE COMPOUNDS FOR TREATING OPHTHALMIC DISEASES AND DISORDERS
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Provided are alkynyl phenyl derivative compounds, pharmaceutical compositions thereof, and methods of treating ophthalmic diseases and disorders, such as age-related macular degeneration and Stargardt's Disease, using said compounds and compositions.
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Page/Page column 181
(2009/03/07)
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- Phosphabarrelenes as ligands in rhodium-catalyzed hydroformylation of internal alkenes essentially free of alkene isomerization
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Despite significant research efforts in the past, one of the remaining problems to be solved in industrially important hydroformylation is the chemoselective low-pressure hydroformylation of internal alkenes. We report here on a new class of phosphabarrelene/rhodium catalysts 2 that display very high activity towards hydroformylation of internal alkenes with an unusually low tendency towards alkene isomerization. Preparation of new phosphabarrelene ligands, studies of their coordination properties, as well as results obtained in the rhodium-catalyzed hydroformylation of cyclic and acyclic internal alkenes are reported.
- Fuchs, Evelyn,Keller, Manfred,Breit, Bernhard
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p. 6930 - 6939
(2007/10/03)
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- DIARYL ETHERS AS OPIOID RECEPTOR ANTAGONIST
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A compound of the formula (I) wherein the variables X1 to X10, R1 to R7 including R3', E, v, y, z, A and B are as described, or a pharmaceutically acceptable salt, solvate, enantiomer, racemate, diastereomer or mixtures thereof, useful for the treatment, prevention or amelioration of obesity and Related Diseases is disclosed.
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Page/Page column 89
(2008/06/13)
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- Phosphabarrelene-rhodium complexes as highly active catalysts for isomerization free hydroformylation of internal alkenes
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A new class of phosphabarrelene-rhodium catalysts is described which allows for the first time hydroformylation of internal alkenes with very high activity and which proceeds essentially free of alkene isomerization.
- Breit, Bernhard,Fuchs, Evelyn
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p. 694 - 695
(2007/10/03)
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- Thermal reactions of oxiranes
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The pyrolytic reactions of tetramethylethylene oxide, cyclopentene oxide, cyclohexene oxide, cyclooctene oxide, 1,2-epoxyethylbenzene, 1,2-epoxy-2-phenylpropane, 1,2-epoxy-1-phenylpropane, and 1,2-epoxy-1,2-diphenylethane were investigated at 600 deg C using a conventional pyrolysis flow system.The products are mainly due to thermal cleavage of the oxirane ring followed by rearrangement to give carbonyl compounds.
- Oyewale, A. O.,Aitken, R. A.
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p. 919 - 922
(2007/10/02)
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- Rhodium complex catalyzed hydroformylation reactions of linear and cyclic mono- and diolefins
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The hydroformylation reactions of cyclopentene, cyclohexene, 4-vinylcyclohexene, cycloheptene and cyclooctene, catalyzed with a Rh(acac)2/P(OPh)3 (I) system at 80 deg C and 10 atm (CO+H2), have been studied.Only cyclopentene and 4-vinylcyclohexene undergo hydroformylation at 1 atm and 40 deg C.The hydroformylation of some cyclic dienes; (1,3- and 1,4-cyclohexadienes, 1,3- and 1,5-cyclooctadienes and 1,3-cyclopentadiene), at 10 atm and 80 deg C, was investigated in two catalytic systems: (I) and Rh(acac) (CO) (PPh3) / PPh3 (II).The main reaction products of cyclohexadienes and pentadiene (at 80 deg C, 10 atm) are unsaturated monoaldehydes.In hydroformylation of 1,5-cyclooctadiene the main product is formylcyclooctane.Key words: Rhodium; Olefins; Hydroformylation
- Trzeciak, Anna M.,Ziolkowski, Jozef J.
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p. 213 - 216
(2007/10/02)
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- Isomerization of Cyclooctene and Cyclododecene Oxides Catalyzed by Solid Acids and Bases
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The title reactions were carried out over seven catalysts.From cyclooctene oxide a large amount of 7-octenal was formed together with 3-cycloocten-1-ol over SiO2-Al2O3 and SiO2-TiO2, 3-cycloocten-1-ol over solid H3PO4, and cyclooctanone over FeSO4.Most catalysts except for NiSO4, Al2O3, and Tio2-ZrO2 produced 1,3-cyclododecadiene, cyclododecanone, and 2-cyclododecen-1-ol uniformly from cyclododecene oxide.Allylic alcohols were preferentially given by Al2O3 and TiO2-ZrO2.
- Arata, Kazushi,Nakamura, Hideo,Nakamura, Yuki
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p. 2351 - 2353
(2007/10/02)
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- Studies on the chemistry of diols and cyclic ethers-53. Dehydration of 1,1-bishydroxymethylcycloalkanes: A quest for a 1,3-hydride shift
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A study of the sulphuric acid-catalysed dehydrations of 1,1-bishydroxymethyl-cyclopropane, - cyclobutane, - cyclopentane and -cyclohexane (1a-1d) revealed that the product distributions are determined by the relative stabilities of carbenium ions and der kinetic control furnished evidence of a 1,3-hydride shift.
- Molnar, Arpad,Bucsi, Imre,Bartok, Mihaly
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p. 4929 - 4936
(2007/10/02)
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- 18-Cycloalkyl Analogues of Enisoprost
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By use of standard cuprate methodology, a series of 18-cycloalkyl analogues of enisoprost was prepared in an effort to impede ω chain metabolism and prolong duration of gastric antisecretory activity.An initial product of ω chain oxidation, the C-20 hydroxy analogue, was also synthesized for pharmacological comparison.The cyclopropyl, cyclobutyl, and cyclopentyl analogues were approximately one-fourth as potent as enisoprost in inhibiting gastric acid secretion, while the cyclohexyl and cycloheptyl analogues showed very weak activity, and the 20-hydroxy compound was inactive at a dose 100 times the ED 50 of enisoprost.The cyclobutyl compound had a longer duration of antisecretory action than enisoprost and the other cycloalkyl analogues.The cycloalkyl analogues unexpectedly possessed low diarrheogenic activity in rats.
- Collins, Paul W.,Gasiecki, Alan F.,Perkins, Willam E.,Gullikson, Gary W.,Jones, Peter H.,Bauer, Raymond F.
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p. 1001 - 1006
(2007/10/02)
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- ISOMERIZATION OF cis-1,2-EPOXY-5-CYCLOOCTENE AND cis-EPOXYCYCLOOCTANE BY ACTION OF LITHIUM AND MAGNESIUM SALTS
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During the isomerization of cis-1,2-epoxy-5-cyclooctene by the action of lithium bromide and lithium iodide and of magnesium bromide etherate and magnesium iodide etherate cis-4-cycloocten-1-one or cis-1-formyl-4-cycloheptene or their mixture are formed predominantly, depending on the conditions.Cyclooctanone is formed with high yields during the isomerization of cis-epoxy-cyclooctane by the action of lithium bromide and lithium iodide.
- Zakharkin, L. I.,Guseva, V. V.,Kamernitskii, D. A.
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- A Convenient Synthesis of Aldehydes by Rearrangement of Cyclic Epoxides with Lithium Bromide on Alumina
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Epoxides can be converted effectively to aldehydes by rearrangement with lithium bromide supported on alumina.In the case of the alicyclic epoxides, ring contracted cycloalkanecarbaldehydes can be formed.The conversion is achieved by gas-phase reaction or in toluene as solvent.
- Suga, Hisashi,Miyake, Hajimu
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p. 394 - 395
(2007/10/02)
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- REACTION OF α,β-UNSATURATED ALDEHYDES WITH HYDROGEN PEROXIDE CATALYSED BY BENZENESELENINIC ACIDS AND THEIR PRECURSORS
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Oxidation of α,β-unsaturated aldehydes with hydrogen perixide catalysed by benzeneselenic acids and their precursors has been investigated.Bis 2-nitrophenyl diselenide has proved to be the most effective catalyst.The major products resulting from the oxidation are vinyl formates (a) which on hydrolysis give saturated aldehydes or ketones (g) having the carbon chain shortened by one carbon atom, compared with the starting aldehydes.The minor products are formyloxyoxiranes (b), α-hydroxycarbonyl (e) and α-formyloxycarbonyl (f) compounds with the carbon chain shortened by one carbon atom.Carbonyl compounds d, formally derived from an oxidative fission of the carbon-carbon double bond, have been also isolated.Diformyloxy (4c) and formyloxyacetoxy phenylmethane (5c) have been isolated when cinnamaldehyde (4) or 1-phenyl-2-formyloxypropane (5a) were oxidized, respectively.Possible mechanisms of formation of these products are discussed.Similar products resulted when α,β-unsaturated aldehydes were oxidized with organic peroxy acids.
- Syper, Ludwik
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p. 2853 - 2872
(2007/10/02)
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- Syntheses with Aliphatic Dialdehydes, XXXVIII. - Synthesis and Properties of Cycloalkylmalonaldehydes
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Vilsmeier formylation of cycloalkyl-substituted enol ethers (7,14a - c,23) yields the cycloalkylmalonaldehydes 1 - 5 for the first time.In solution 1 - 5 exist in the (E)-s-(E) enol form as vinylogous carboxylic acids.The reaction of 1 - 5 with suitable electrophiles and nucleophiles leads to cycloalkyl-substituted open-chain (29,30), carbocyclic (31) as well as heterocyclic compounds (32-40) with peculiar properties due to the presence of the lipophilic cycloalkyl group.
- Reichardt, Christian,Ferwanah, Abdel-Rahman,Pressler, Wilfried,Yun, Kyeong-Yeol
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p. 649 - 679
(2007/10/02)
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- SILICON IN SYTHESIS-17 CHLROMETHYL(TRIMETHYLSILYL)LITHIUM-A NEW REAGENT FOR THE DIRECT CONVERSION OF ALDEHYDES AND KETONES INTO α,β-EPOXYTRIMETHYLSILANES
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Treatment of chloromethyltrimethylsilane 1 with sec-BuLi at -78 deg produces chloromethyl(trimethylsilyl)lithium 4.Treatment of 4 with a wide range of aldehydes and ketones gives α,β-epoxytrimethylsilanes 5-28, which on acidic hydrolysis give homologated aldehydes.
- Burford, Clifford,Cooke, Frank,Roy, Glenn,Magnus, Philip
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p. 867 - 876
(2007/10/02)
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- Importance of the Aromatic Ring in Andrenergic Amines. 5. Nonaromatic Analogues of Phenylethanolamine as Inhibitors of Phenylethanolamine N-Methyltransferase: Role of Hydrophobic and Steric Interactions
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The synthesis of five classes of nonaromatic analogues of β-phenylethanolamine and an evaluation of their inhibitory potency (IC50) for phenylethanolamine N-methyltransferase (PNMT) are described.The key intermediates for the synthesis of the ethanolamines were the appropriate aldehydes or ketones.The aldehydes 11a (cyclobutyl) and 13a (cycloheptyl) of type A were prepared from the correspondingacids by reduction of the acid to the alcohol with lithium aluminum hydride and oxidation of the alcohol to the aldehyde with pyridinium chlorochromate (PCC).The aldehydes 15a (cycloundecyl) and 41a (adamantyl) of type A were prepared by oxidation of the corresponding alcohols with PCC.The first reported synthesis of cyclononanecarboxaldehyde (type A, 14a) is described.This aldehyde was prepared via a multistep route beginning with a Favorskii rearrangement of 2-bromocyclodecanone to cyclononanecarboxylic acid.The acid was reduced with lithium aluminum hydride to the corresponding alcohol, which was subsequently oxidized to the aldehyde with PCC.The aldehydes or ketones were converted (with trimethylsilyl cyanide) into their cyanohydrin ethers, which were subsequently reduced to the desired ethanolamine with lithium aluminum hydride.The ethanolamines were tested as inhibitors (LCEC assay) of PNMT.The most potent inhibitors were the type A compounds 8 (cyclooctyl), 13c (cycloheptyl), 14c (cyclononyl), and 15c (cycloundecyl) and the type D compounds 26c (cyclononyl) and 27c (cycloundecyl) with IC50 values from 6 to 17 μM.It isconcluded that the binding site of PNMT accepts hydrophobic groups of an optimal length (ca. 6.4 Angstroem) and width (ca. 2.5 Angstroem) and has a significant height restriction for the hydrophobic group.The ethanolamine side chain prefers to lie away from and in the longitudinal axis of the hydrophobic group.An ethanolamine side chain attached to a cycloalkyl ring of n carbon atoms (types A and D) is almost always considerably more potent at inhibiting PNMT than the open-chain compounds of n total carbon atoms (types B, C, and E).
- Vincek, William C.,Aldrich, Constance S.,Borchardt, Ronald T.,Grunewald, Gary L.
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