- Iron-Catalyzed Diastereoselective Synthesis of Disubstituted Morpholines via C-O or C-N Bond Formation
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The diastereoselective synthesis of 2,6- and 3,5-disubstituted morpholines was achieved from 1,2-amino ethers and 1,2-hydroxy amines substituted by an allylic alcohol using an iron(III) catalyst. The morpholines were obtained either by C-O or C-N bond formation. A plausible mechanism is suggested, involving a thermodynamic equilibrium to explain the formation of the cis diastereoisomer as the major product.
- Aubineau, Thomas,Dupas, Alexandre,Zeng, Tian,Cossy, Janine
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supporting information
p. 525 - 531
(2020/08/28)
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- Iron-catalyzed alkyne-carbonyl metathesis for the synthesis of 6,7-dihydro-5H-dibenzo[c,e]azonines
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The synthesis of nine-membered ringsviaalkyne-carbonyl metathesis is reported. The alkyne and acetal units contained in a biaryl substrate undergo the intramolecular alkyne-carbonyl metathesis reaction under FeCl3-catalysis to furnish the unexp
- Chakraborty, Baitan,Jana, Umasish
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supporting information
p. 10549 - 10553
(2021/12/27)
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- Copper-catalyzed cycloisomerization of unactivated allene-tethered O-propargyl oximes: A domino reaction sequence toward the synthesis of hexahydropyrrolo[3,4- b]azepin-5(4 H)-ones
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A novel copper-catalyzed cycloisomerization of unactivated allene-tethered O-propargyl oximes has been developed for the synthesis of hexahydropyrrolo[3,4-b]azepin-5(4H)-ones. This one-pot domino reaction proceeds via a [2,3]-sigmatropic rearrangement, a
- Nikbakht, Ali,Amiri, Kamran,Khosravi, Hormoz,Zhou, Yirong,Balalaie, Saeed,Breit, Bernhard
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supporting information
p. 3343 - 3348
(2021/05/07)
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- Palladium-Catalyzed C(sp3)?H Arylation of Primary Amines Using a Catalytic Alkyl Acetal to Form a Transient Directing Group
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C?H Functionalization of amines is a prominent challenge due to the strong complexation of amines to transition metal catalysts, and therefore typically requires derivatization at nitrogen with a directing group. Transient directing groups (TDGs) permit C?H functionalization in a single operation, without needing these additional steps for directing group installation and removal. Here we report a palladium catalyzed γ-C?H arylation of amines using catalytic amounts of alkyl acetals as transient activators (e.g. commercially available (2,2-dimethoxyethoxy)benzene). This simple additive enables arylation of amines with a wide range of aryl iodides. Key structural features of the novel TDG are examined, demonstrating an important role for the masked carbonyl and ether functionalities. Detailed kinetic (RPKA) and mechanistic investigations determine the order in all reagents, and identify cyclopalladation as the turnover limiting step. Finally, the discovery of an unprecedented off-cycle free-amine directed ?-cyclopalladation of the arylation product is reported.
- St John-Campbell, Sahra,Ou, Alex K.,Bull, James A.
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supporting information
p. 17838 - 17843
(2018/11/23)
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- Synthesis of Indole-Dihydroisoquinoline Sulfonyl Ureas via Three-Component Reactions
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Isoquinolines activated with sulfamoyl chlorides were reacted with indoles in a 3-component reaction to generate a library of dihydroisoquinoline derivatives. Using a differential protecting group strategy, products could be further derivatised. Synthesis of isoquinoline starting materials using several different methods is also described.
- Pearson, Stuart E.,Fillery, Shaun M.,Goldberg, Kristin,Demeritt, Julie E.,Eden, Jonathan,Finlayson, Jonathan,Patel, Anil
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p. 4963 - 4981
(2018/12/13)
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- α-Amino Aldehydes as Readily Available Chiral Aldehydes for Rh-Catalyzed Alkyne Hydroacylation
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Readily available α-amino aldehydes, incorporating a methylthiomethyl (MTM) protecting group on nitrogen, are shown to be efficient substrates in Rh-catalyzed alkyne hydroacylation reactions. The reactions are performed under mild conditions, employing a small-bite-angle bis-phosphine ligand, allowing for good functional group tolerance with high stereospecificity. Amino aldehydes derived from glycine, alanine, valine, leucine, phenylalanine, isoleucine, serine, tryptophan, methionine, and cysteine were successfully employed, as was an enantiomerically enriched α-OMTM-aldehyde derived from phenyllactic acid. The synthetic utility of the α-amino enone products is demonstrated in a short enantioselective synthesis of the natural product sphingosine.
- Hooper, Joel F.,Seo, Sangwon,Truscott, Fiona R.,Neuhaus, James D.,Willis, Michael C.
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supporting information
p. 1630 - 1634
(2016/02/20)
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- Gold-Catalyzed Fluorination–Hydration: Synthesis of α-Fluorobenzofuranones from 2-Alkynylphenol Derivatives
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The AuI-catalyzed fluorination–hydration of 2-alkynylphenol derivatives in the presence of Selectfluor [1-chloromethyl-4-fluoro-1,4-diazoniabicyclo-[2.2.2]octane bis(tetrafluoroborate)] has been developed. This method provides straightforward a
- Wang, Qiang,Jiang, Yu,Sun, Run,Tang, Xiang-Ying,Shi, Min
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supporting information
p. 14739 - 14745
(2016/10/03)
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- Access to Polyfunctionalized Chiral Piperidines through Enantioselective Addition-Carbocyclization Cascade Reaction Catalyzed by a Rhodium(I)-Diene Complex
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A new addition-carbocyclization cascade reaction initiated by arylboronic acids and catalyzed by a rhodium/chiral diene complex is described. Starting from N-bridged oxoenoate derivatives, highly functionalized piperidines bearing three contiguous stereogenic centers were obtained with excellent enantio- and diastereoselectivities.
- Serpier, Fabien,Brayer, Jean-Louis,Folléas, Beno?t,Darses, Sylvain
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supporting information
p. 5496 - 5499
(2015/11/18)
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- Vinyl dihydropyrans and dihydrooxazines: Cyclizations of catalytic ruthenium carbenes derived from alkynals and alkynones
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A novel synthesis of 2-vinyldihydropyrans and dihydro-1,4-oxazines (morpholine derivatives) from alkynals and alkynones has been developed. The cyclizations require a mild generation of catalytic ruthenium carbenes from terminal alkynes and (trimethylsilyl)diazomethane followed by trapping with carbonyl nucleophiles. Mechanistic aspects of the new cyclizations are discussed. Setting a trap: A novel synthesis of 2-vinyldihydropyrans and dihydro-1,4-oxazines (morpholine derivatives) from alkynals and alkynones has been developed. The cyclizations require a mild generation of catalytic ruthenium carbenes from terminal alkynes and (trimethylsilyl)diazomethane followed by trapping with carbonyl nucleophiles.
- Cambeiro, Fermin,Lopez, Susana,Varela, Jesus A.,Saa, Carlos
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supporting information
p. 5959 - 5963
(2014/06/10)
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- Gold-catalyzed intramolecular regio- and enantioselective cycloisomerization of 1,1-bis(indolyl)-5-alkynes
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Bis(indole) alkaloids analogues were prepared under mild conditions and in high yields through a gold-catalyzed cycloisomerization of 1,1-bis(indolyl)-5- alkynes (see scheme). The enan Copyright
- Huang, Long,Yang, Hai-Bin,Zhang, Di-Han,Zhang, Zhen,Tang, Xiang-Ying,Xu, Qin,Shi, Min
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supporting information
p. 6767 - 6771
(2013/07/25)
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- Diversity-oriented synthesis of hydrazine-derived compounds from amino isocyanates generated in situ
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Behind the mask: Nitrogen-substituted isocyanates are rare and their synthetic potential is virtually untapped. Simple masked precursors can form amphoteric amino isocyanate intermediates in situ, and allows the synthesis of complex hydrazine derivatives upon addition with amines. This reactivity was used in a cascade substitution/hydroamination sequence, and in the assembly of azadipeptide analogues. Copyright
- Clavette, Christian,Vincent Rocan, Jean-Francois,Beauchemin, Andre M.
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supporting information
p. 12705 - 12708
(2013/12/04)
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- Cationic rhodium(I)/H8-binap complex catalyzed [2+2+2] cycloadditions of 1,6- And 1,7-diynes with carbonyl compounds
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We have established that a cationic rhodium(I)/H8-binap complex catalyzes [2+2+2] cycloadditions of a variety of 1,6and 1,7-diynes with both electron-deficient and electron-rich carbonyl compounds, leading to dienones in high yield under mild reaction conditions. In the reactions with acyl phosphonates, the reactivity of 1,6- and 1,7-diynes was highly dependent on their own structures. The addition of chelating diethyl oxalate effectively promoted the [2+2+2] cycloadditions involving acyl phosphonates, presumably due to the equilibrium formation of the desired 1:1 rhodium complex of the diyne and the acyl phosphonate by facile ligand exchange between the diyne and weakly coordinated diethyl oxalate. In the reactions involving bifunctional carbonyl compounds or unsymmetrical 1,6-diynes, high chemo- or regioselectivities were observed. Wiley-VCH Verlag GmbH & Co. KGaA.
- Otake, Yousuke,Tanaka, Rie,Tanaka, Ken
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supporting information; experimental part
p. 2737 - 2747
(2009/08/09)
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- Hydrazides as tunable reagents for alkene hydroamination and aminocarbonylation
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(Chemical Equation Presented) Benzoic hydrazides (R = Ph), which are remarkably bench and thermally stable reagents (often up to 230°C), afford intramolecular hydroamination products upon heating at high temperatures (120-235°C). A concerted Cope-type hydroamination event, followed by a hydrazide-mediated proton transfer step of the hydrazinium ylide intermediate, is proposed and supported by DFT calculations. In contrast, a simple modification of the reagent structure (R = Ot-Bu or NH2) favors the formation of aminocarbonylation products at 200°C, and the latter reaction is shown to be stereospecific. Copyright
- Roveda, Jean-Gregoire,Clavette, Christian,Hunt, Ashley D.,Gorelsky, Serge I.,Whipp, Christopher J.,Beauchemin, Andre M.
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supporting information; experimental part
p. 8740 - 8741
(2009/12/04)
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- 5-SUBSTITUTED 2H-PYRAZOLE-3-CARBOXYLIC ACID DERIVATIVES AS AGONISTS FOR THE NICOTINIC ACID RECEPTOR RUP25 FOR THE TREATMENT OF DYSLIPIDEMIA AND RELATED DISEASES
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The present invention relates to certain pyrazole carboxylic acid and ester derivatives, and pharmaceutically acceptable salts thereof, which exhibit useful pharmaceutical properties, for example as agonists for the RUP25 receptor. (I) Also provided by the present invention are pharmaceutical compositions containing compounds of the invention, and methods of using the compounds and compositions of the invention in the prophylaxis or treatment of metabolic-related disorders, including dyslipidemia, atherosclerosis, coronary heart disease, insulin resistance, type 2 diabetes, Syndrome-X and the like. In addition, the present invention also provides for the use of the compounds of the invention in combination with other active agents such as those belonging to the class of α -glucosidase inhibitors, aldose reductase inhibitors, biguanides, HMG-CoA reductase inhibitors, squalene synthesis inhibitors, fibrates, LDL catabolism enhancers, angiotensin converting enzyme (ACE) inhibitors, insulin secretion enhancers and the like.the substituents are defined in claim 1.
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Page/Page column 91
(2008/06/13)
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- Catalytic Asymmetric Intramolecular α-Alkylation of Aldehydes
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The development of a general catalytic asymmetric aldehyde α-alkylation reaction constitutes a major challenge in organic synthesis. Here, we report the first and successful approach toward its solution: (S)-α-methyl proline catalyzes the intramolecular a
- Vignola, Nicola,List, Benjamin
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p. 450 - 451
(2007/10/03)
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- Radical cyclization in heterocycle synthesis. Part 13: Sulfanyl radical addition-cyclization of oxime ethers and hydrazones connected with alkenes for synthesis of cyclic β-amino acids
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A combination of sulfanyl radical addition-cyclization of the oxime ethers and hydrazones connected with alkenes and subsequent conversion of a phenylsulfanylmethyl group to a carboxyl group provides a novel method for the construction of the cyclic β-amino acids. Upon treatment with thiophenol in the presence of AIBN, the oxime ethers and hydrazones smoothly underwent sulfanyl radical addition-cyclization to give the 2-(phenylsulfanylmethyl)cycloalkylamine. This method was successfully applied to the practical synthesis of 2-aminocyclopentanecarboxylic acid and 4-amino-3-pyrrolidinecarboxylic acid.
- Miyata, Okiko,Muroya, Kanami,Kobayashi, Tomoko,Yamanaka, Rina,Kajisa, Seiko,Koide, Junko,Naito, Takeaki
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p. 4459 - 4479
(2007/10/03)
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- AMINOISOQUINOLINE DERIVATIVES
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Aminoisoquinoline derivatives represented by formulae (I and II), analogs thereof or pharmaceutically acceptable salts of the same. Because of having excellent inhibitory effects on activated blood coagulation factor X, these compounds are useful as active ingredients in anticoagulants or preventives/remedies for thrombosis or embolism.
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- Preparation and cyclopropanation of selected oxapolycycles
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The Diels-Alder reaction of dimethyl furandicarboxylate 6 with DMAD is investigated and the exo-exo bisadduct 8 is fully characterized. Monoadduct 7, 8, and test system 12 are cyclopropanated with diazomethane giving 10, 11, and 14. Then 7, 8, and 12 are
- Sander, Michael,Dehmlow, Eckehard Volker,Neumann, Beate,Stammler, Hans-Georg
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p. 13395 - 13406
(2007/10/03)
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- Reductive Cyclization of Ketones Tethered to Activated Olefins Mediated by Magnesium in Methanol
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The reductive cyclization of various ketones tethered to activated olefins such as α,β-unsaturated esters, nitriles, sulfoxides, and sulfides mediated by magnesium in dry methanol in the presence of mercuric chloride.When traeted with magnesium in dry methanol at -23 deg C all of the ketones except nitrile 9 (42percent) and 5-oxa-8-keto-2-enoate 5 (13percent) gave excellent yields (79-98percent) of mono- and bicyclic alcohol products resulting from carbon-carbon bond formation between the β-carbon of the activated olefin and the carbonyl carbon.The reaction was accelerated by the catalytic amount of mercuric chloride, although the stereoselectivity was not affected by the catalyst.For all the substrates except 8-keto-2-enoate 3 and 5-aza-8-keto-2-enoate 6, the configuration of the major product was trans between the hydroxy and (methoxycarbonyl)methyl groups.The product isomer ratios were independent of the substrate geometry (E or Z).In contrast to the ketones, aldehydes tethered to α,β-unsaturated esters gave products of simple reduction of the double bond and/or saturated alcohols instead of the cyclized products.When the reaction temperature was lowered, the yields of cyclized product were significantly affected by the production of appreciable amounts of saturated product, but the stereoselectivity was not improved.Under the same reaction conditions α,β-unsaturated sulfoxide 16 gave deoxygenated sulfide 18 (85percent) as the major product along with a small amount (9percent) of cyclized product 19t.In contrast, sulfone 17 underwent desulfonylation instead of cyclization to give olefin 20 (54percent).With excess magnesium (15 equiv), however, α,β-unsaturated sulfoxide 16 gave cyclized sulfide 19t (95percent) via deoxygenated sulfide 18.Both 16Z and 16E afforded product 19t as a single isomer.It is suggested that the reductive cyclization of the α,β-unsaturated esters and nitriles proceed by means of nucleophilic attack of a β-carbon radical anion, formed by initial electron transfer from magnesium metal to the activated olefin, on the carbonyl group.The cyclization of the α,β-unsaturated sulfide proceeds by nucleophilic attack of the ketyl on the olefinic double bond.
- Lee, Ge Hyeong,Choi, Eun Bok,Lee, Eun,Pak, Chwang Siek
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p. 1428 - 1443
(2007/10/02)
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- Electroorganic chemistry. 120. New patterns of anodic oxidation of amides. Synthesis of α-amino aldehyde acetals and pyrrolidines from amines
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Anodic oxidation of N-alkyltosylamides 1 in methanol containing KX (X = Br, I) gave two types of products, α-(tosylamino) aldehyde acetals 2 and pyrrolidine derivatives 3, and each of the products could selectively be formed by modifying the reaction conditions when the alkyl group on the nitrogen of 1 was not branched at its α-position. Namely, anodic oxidation ot N-(α-unbranched alkyl)tosylamides 1a-g in methanol containing NaOMe and KI at -10°C followed by further anodic oxidation at 25°C afforded 2 in good yields, while that of 1 in a two-layer system consisting of cyclohexane and water containing KOH and KBr under heating yielded solely 3. On the other hand, N-(α-branched alkyl)tosylamides 1h-j gave always 3. Two types of reaction routes leading to each of the products were proposed.
- Shono, Tatsuya,Matsumura, Yoshihiro,Katoh, Susumu,Takeuchi, Kei,Sasaki, Katsushi,Kamada, Tohru,Shimizu, Rie
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p. 2368 - 2372
(2007/10/02)
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- ELECTROOXIDATIVE REARRANGEMENT OF TOSYLAMINO GROUP: FACILE SYNTHESIS OF α-AMINO ALDEHYDES FROM PRIMARY AMINES
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Anodic axidation of primary N-tosylamines in methanol containing halide ion gave α-(N-tosylamino) aldehyde dimethyl acetals, synthetically useful intermediates equivalent to α-amino aldehydes.
- Shono, Tatsuya,Matsumura, Yoshihiro,Katoh, Susumu,Inoue, Kenji,Matsumoto, Yonetatsu
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p. 6083 - 6086
(2007/10/02)
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- A SIMPLIFIED ISOQUINOLINE SYNTHESIS
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A simple variation of the Pomeranz-Fritsch cyclization provides a short, efficient route to isoquinolines.Treatment of benzylic halides or mesylates 1 with the sodium anion of N-tosyl aminoacetaldehyde dimethyl acetal (2) followed by acid-catalyzed cyclization provides an effective, two-step preparation of isoquinolines 4.
- Boger, Dale L.,Brotherton, Christine E.,Kelley, Marshall D.
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p. 3977 - 3980
(2007/10/02)
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