- Facile synthesis of fluorovinyl-containing lactams via ring-closing metathesis of N-substituted 2-fluoroallylamides
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A cost-efficient method for the preparation of a series of N-substituted 2-fluoroallylamines and their application in the synthesis of fluoroalkene-containing lactams are described. N-substituted 2-fluoroallylamine could be readily synthesized from methyl 2-fluoroacrylate via aminolysis and subsequently selective reduction of the amide group. These amines were further converted into the corresponding amides with diverse acids bearing a terminal double bond. The Ring-Closing Metathesis (RCM) of the resulting amides led to the formation fluorovinyl-containing lactams in good yields.
- Li, Yang,Li, Kai,Wu, Yue,Ma, Qiaoning,Lei, Xinsheng
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- Substrate encapsulation: An efficient strategy for the RCM synthesis of unsaturated ε-lactones
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(Chemical Equation Presented) A facile substrate-encapsulated RCM-based synthesis of 7-membered lactones is reported. Coordination of the α,ω-dienyl ester precursor to the bulky Lewis acid (LA) aluminum tris(2,6-diphenylphenoxide) (ATPH) provides a protective extended steric pocket to the olefin moieties, thereby favoring intramolecular RCM over intermolecular ADMET oligomerization. The LA-encapsulated esters undergo ring-closure in the presence of Ru-based olefin metathesis catalysts to give previously difficult-to-access 7-membered β,γ- and γ,δ-unsaturated lactones in good yields.
- Pentzer, Emily B.,Gadzikwa, Tendai,Nguyen, Sonbinh T.
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- Synthesis of 1,3-bridged β-lactams embedded in a macrocyclic structure
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A new approach to N1-C3 bridged macrocyclic β-lactams has been developed. Orthogonal functional groups' protection combined with RCM has allowed the construction of the bicyclic systems bearing a β-lactam motif. These systems could represent a structural alternative to the actual lactamic antibiotics and may be further transformed into a broad variety of compounds.
- Sierra, Miguel A.,Rodríguez-Fernández, Mamen,Manche?o, María José,Casarrubios, Luis,Gómez-Gallego, Mar
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- Sulfoxide ligand metal catalyzed oxidation of olefins
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The enantioselective synthesis of isochroman motifs has been accomplished via Pd(II)-catalyzed allylic C—H oxidation from terminal olefin precursors. Critical to the success of this goal was the development and utilization of a novel chiral aryl sulfoxide-oxazoline (ArSOX) ligand. The allylic C—H oxidation reaction proceeds with the broadest scope and highest levels asymmetric induction reported to date (avg. 92% ee, 13 examples ≥90% ee). Additionally, C(sp3)-N fragment coupling reaction between abundant terminal olefins and N-triflyl protected aliphatic and aromatic amines via Pd(II)/sulfoxide (SOX) catalyzed intermolecular allylic C—H amination is disclosed. A range of 52 allylic amines are furnished in good yields (avg. 76%) and excellent regio- and stereoselectivity (avg. >20:1 linear:branched, >20:1 E:Z). For the first time, a variety of singly activated aromatic and aliphatic nitrogen nucleophiles, including ones with stereochemical elements, can be used in fragment coupling stiochiometries for intermolecular C—H amination reactions.
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Page/Page column 127
(2019/05/09)
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- C-H to C-N Cross-Coupling of Sulfonamides with Olefins
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Cross-coupling of nitrogen with hydrocarbons under fragment coupling conditions stands to significantly impact chemical synthesis. Herein, we disclose a C(sp3)-N fragment coupling reaction between terminal olefins and N-triflyl protected aliphatic and aromatic amines via Pd(II)/SOX (sulfoxide-oxazoline) catalyzed intermolecular allylic C-H amination. A range of (56) allylic amines are furnished in good yields (avg. 75%) and excellent regio- and stereoselectivity (avg. >20:1 linear:branched, >20:1 E:Z). Mechanistic studies reveal that the SOX ligand framework is effective at promoting functionalization by supporting cationic π-allyl Pd.
- Ma, Rulin,Christina White
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supporting information
p. 3202 - 3205
(2018/03/13)
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- Dehydrogenative Allylic Aminations of But-3-enoic Acid Derivatives
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Two complementary Pd-catalyzed protocols enabling the γ-selective intermolecular allylic amination of but-3-enoic acid derivatives are reported. These transformations can be successfully achieved via either a direct Pd(II)-catalyzed protocol or by way of a one-pot Pd(II)/Pd(0)-catalyzed sequence, depending on the nature of the nitrogen nucleophile used.
- Diamante, Daria,Gabrieli, Sara,Benincori, Tiziana,Broggini, Gianluigi,Oble, Julie,Poli, Giovanni
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supporting information
p. 3400 - 3412
(2016/09/12)
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- Synthesis of α-chiral-β,γ-unsaturated carboxylic acid derivatives using chiral auxiliaries
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We report an efficient and reliable method for the synthesis of α-chiral-β,γ-unsaturated carboxylic acid derivatives using chiral auxiliaries and vinylacetic acid. Two well-established chiral auxiliaries ((S,S)-pseudoephedrine and (R)-benzyl-oxazolidinone) were chosen to test the merits of this method. Six different electrophiles were examined in the diastereoselective alkylation with both auxiliaries. The pseudoephedrine auxiliary provided isolated yields between 61 and 85% and diastereomeric ratios all greater than 96:4. Employing the same reactions as with the pseudoephedrine derivative, the corresponding oxazolidinone auxiliary provided isolated yields between 0 and 80% with diastereomeric ratios from 80:20 to 93:7.
- Poremba, Kelsey E.,Lee, Victoria A.,Sculimbrene, Bianca R.
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p. 5463 - 5467
(2015/03/30)
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- Platinum-catalyzed intramolecular hydrohydrazination: Evidence for alkene insertion into a Pt-n bond
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Dicationic (bpy)Pt(II) complexes were found to catalyze the intramolecular hydrohydrazination of alkenes. Reaction optimization revealed Pt(bpy)Cl 2 (10 mol %) and AgOTf (20 mol %) in DMF-d7 to be an effective catalyst system for the conversion of substituted hydrazides to five- and six-membered N-amino lactams (N-amino = N-acetamido at 120 A°C, N-phthalimido at 80 A°C, -OTf = trifluoromethanesulfonate). Of the four possible regioisomeric products, only the product of 5-exo cyclization at the proximal nitrogen is formed, without reaction at the distal nitrogen or 6-endo cyclization. The resting states were found to be a 2:1 Pt-amidate complex (25, for N-acetamido) of the deprotonated hydrazide and a Pt-alkyl complex of the cyclized pyrrolidinone (20 for N-phthalimido). Both complexes are catalytically competent. Catalysis using 25 as the precatalyst shows no rate dependence on added acid (HOTf) or base (2,6-lutidine). The available mechanistic data are all consistent with a mechanism involving N-H activation of the hydrazide, followed by insertion of the alkene into the Pt-N bond, and finally protonation of the resulting cyclized alkyl complex by hydrazide to release the hydrohydrazination product and regenerate the active Pt-amidate catalyst.
- Hoover, Jessica M.,Dipasquale, Antonio,Mayer, James M.,Michael, Forrest E.
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supporting information; body text
p. 5043 - 5053
(2010/06/13)
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- Synthesis of oxazinyl analogues of fosmidomycin using RCM methodology
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Fosmidomycin is a promising antimalarial compound with a novel mode of action, the inhibition of 1-deoxy-D-xylulose 5-phosphate reductoisomerase, a key enzyme in the biosynthesis of isoprenoids through the nonmevalonate pathway. This paper describes the synthesis of a series of analogues in which the hydroxamate moiety is incorporated in a ring structure, leaving the complexation with the enzyme up to the oxygen lone pairs instead of the free hydroxyl group. The antimalarial activities of the different analogues are currently under investigation. Georg Thieme Verlag Stuttgart.
- Van Der Jeught, Sarah,Stevens, Christian V.,Dieltiens, Nicolai
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p. 3183 - 3187
(2008/09/19)
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- Ligand effects in the synthesis of N-heterocycles by intramolecular Heck reactions
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Chemo- and regioselectivity of intramolecular Heck reactions are dependent on the type of ligand employed. Six- to eight-membered benzolactams are produced in good yields using PPh3 as ligand. In contrast, a biaryl coupling occurred preferentially under ligandless conditions to form a dihydrophenanthridine product. Conformations of the seven- and eight-membered benzolactams in the solid state were examined by X-ray crystallography.
- Cropper, Emma L.,White, Andrew J. P.,Ford, Agnes,Hii, King Kuok
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p. 1732 - 1735
(2007/10/03)
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- Homolytic fragmentation of allyloxychlorocarbene
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(Chemical Equation Presented) The decomposition of allyloxychlorocarbene in hydrocarbon solvents leads via homolysis to allyl and COCl radicals, which recombine to 3-butenoyl chloride or (after scission of ?COCl to CO and ?Cl) to all
- Moss, Robert A.,Ma, Yan,Fu, Xiaolin,Sauers, Ronald R.
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p. 2055 - 2058
(2007/10/03)
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- Comparative reactivity of N′-(5-benzoyl/ethoxycarbonyl)thiazol-2-yl- N,N-dimethylformamidines with ketenes
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The comparative account of the reactivities of N′-[(5-benzoyl and ethoxycarbonyl)thiazol-2-yl]-N,N-dimethylformamidines (1a and 1b), tremendously influenced by the electronic nature of the substituents on C-5 of the thiazolic ring with various monosubstituted and conjugated ketenes is reported herein. The DA cycloadditions of the dienyl pyrimidinone 3h with both symmetrical as well as unsymmetrical dienophiles leading to the formation of various thiazolic pyrimidinone derivatives are also reported.
- Singh, Parvesh,Marwaha, Alka,Singh, Harmeet,Mahajan, Mohinder P.
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p. 11999 - 12005
(2007/10/03)
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- Inhibitors of type I MetAPs containing pyridine-2-carboxylic acid thiazol-2-ylamide. Part 1: SAR studies on the determination of the key scaffold
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Systematic SAR studies on the HTS hit pyridine-2-carboxylic acid thiazol-2-ylamide (PACT) analogues revealed that the scaffold of PCAT is indispensable for the inhibition of type I MetAP. For effective inhibition of the enzyme, the most suitable position to modify is the 3-position of the pyridine ring of PCAT, and the best substituents are those containing O or N atoms connected directly with the pyridine ring. These findings provide useful information for the design and discovery of more potent inhibitors of type I MetAPs.
- Luo, Qun-Li,Li, Jing-Ya,Liu, Zhi-Ying,Chen, Ling-Ling,Li, Jia,Ye, Qi-Zhuang,Nan, Fa-Jun
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p. 635 - 638
(2007/10/03)
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- Aniline disulfide derivatives for treating allergic diseases
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Methods and compositions for preventing or treating allergic diseases of the eye, nose, skin, ear, gastrointestinal tract, airways or lung and preventing or treating manifestations of systemic mastocytosis are disclosed. The compositions contain a mast cell stabilizing disulfide derivative as an active ingredient.
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- 2-cyano-3-hydroxy-enamides
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A compound selected from the group consisting of a compound of the formula STR1 wherein R1 is selected from the group consisting of STR2 R13, R14 and R15 are individually selected from the group consisting of hydrogen, halogen and alkyl of 1 to 3 carbon atoms, n is an integer from 1 to 3, R2 is hydrogen or alkyl of 1 to 3 carbon atoms, R3, R4 R5, R6 and R7 are individually selected from the group consisting of hydrogen, halogen, --NO2, --CN, alkyl, alkylthio and alkoxy of 1 to 6 carbon atoms, alkylcarbonyl of 2 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, STR3 m is 0, 1, 2 or 3, n is 1, 2 or 3; Hal, Hal1, Hal2 and Hal3 are individually halogen and STR4 R8, R9, R10, R11 and R12 are individually any of the groups defined above for R3, R4, R5, R6 and R7 or R4 and R5 together form --O--CH2 --O-- and their non-toxic, pharmaceutically acceptable base addition salts having anti-inflammatory activity.
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- Stereoselective syntheses of substituted 5,6-dihydro-2(1H)-pyridinones in polyphosphate media
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δ-Lactams have been synthesized with excellent stereocontrol of substituents by condensing 3-alkenamides with aryl aldehydes in polyphosphoric ester. The scope of the condensation of 3-alkenamides with aryl aldehydes in several phosphate media is examined, and a rationale is proposed regarding γ-lactam versus δ-lactam formation.
- Marson,Grabowska,Fallah,Walsgrove,Eggleston,Baures
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p. 291 - 296
(2007/10/02)
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- Chlorocarbonylation of Unsaturated Substrates Catalysed by Palladium Complexes in the Presence of Anhydrous HCl
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Chloroacyl halides are obtained under mild conditions by catalytic carbonylation of allylic halides or ethene and allyl chloride under CO and anhydrous HCl pressure; excellent selectivities for formation of dichloroacyl and chloroacyl derivatives are achi
- Benard, Nathalie,Bonnet, Michel C.,Lecolier, Serge,Tkatchenko, Igor
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p. 1448 - 1450
(2007/10/02)
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- Intramolecular and intermolecular Diels-Alder reactions of acylhydrazones derived from methacrolein and ethylacrolein
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The intramolecular Diels-Alder reactions of hydrazones derived from methacrolein or ethylacrolein and terminally unsaturated N-acyl-N-methylhydrazines have been investigated. The hydrazones 7b and 7c derived from N-methyl-N-pent-4-enoylhydrazine 3b were found to undergo intramolecular [4 + 2] cycloaddition above 140°C and the pyridopyridazones 12 were isolated. The corresponding hydrazones 8b and 8c from N-methyl N-pent-4-ynoylhydrazone 4a reacted similarly and gave as the final products the pyridines 13. The scope of the reaction is limited, as was shown by the failure of several other terminally unsaturated hydrazones of αβ-unsaturated aldehydes to undergo intramolecular cycloaddition. These hydrazones did, however, undergo intermolecular [4 + 2] cycloaddition to N-phenylmaleimide. Other hydrazones 15 of methacrolein, including the benzoylhydrazone and the phenylhydrazone, also reacted with N-phenylmaleimide to give the pyridine 14b by way of an isolable dihydropyridine 16.
- Allcock,Gilchrist,Shuttleworth,King
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p. 10053 - 10064
(2007/10/02)
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- Influence of the β-Substitution on the Photochemistry of α,2-Diacetoxystyrenes. Irradiatin of Phenyl, Vinyl, and Benzyl Derivatives
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β-Substitution shows a pronounced influence on the photochemistry of α,2-diacetoxystyrenes.As in the case of the parent compound, intramolecular cyclization with participation of the neighbouring 2-acetoxy group takes place upon irradiation of the enol esters 4a-c; however other processes are also observed, depending on the substrate.The phenyl derivative 4a gives the E isomer 7a and the phenanthrene 9.The vinyl derivative 4b also undergoes cis-trans isomerization and/or photooxidation, to afford 7b and 10.Finally, a 1,4-acyl migratin occurs in the benzyl derivative 4c, whereby the 1,4-diketone 12 is formed.
- Alvaro, Mercedes,Baldovi, Vicenta,Garcia, Hermenegildo,Miranda, Miguel, A.,Primo, Jaime
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p. 267 - 274
(2007/10/02)
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- A New Synthesis of (R)-GABOB and (R)-Oxiracetam
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The synthesis of both (R)-GABOB 1 and (R)-Oxiracetam 2 through the same diastereomer intermediate 8a is reported.
- Orena, Mario,Porzi, Gianni,Sandri, Sergio
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p. 2701 - 2711
(2007/10/02)
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- Synthesis and Reactions of Iodo Lactams
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The synthesis of a series of iodo lactams has been achieved by a new cyclization method that depends on generating N,O-bis(trimethylsilyl)imidate derivatives as intermediates.Treatment of an unsaturated amide with trimethylsilyl triflate in pentane and then iodine in tetrahydrofuran gives the iodo lactam.Some reactions of this new difunctional group with bases, nucleophiles, and Michael acceptors leading to functionalized or elaborated lactams are presented.In general, iodo lactams undergo direct SN2 reactions with reactive (but weakly basic) nucleophiles like azide and triphenylphosphine and elimination or decomposition in the presence of bases or basic nucleophiles.Sodium hydride may be used to generate an N-acylaziridine intermediate, which can be opened with azide to deliver an azido lactam with overall retention of stereochemistry.Silver-assisted solvolysis of iodo lactams gives the hydroxy lactams with retention of configuration, probably also because of participation by the lactam nitrogen.The sodium salt of 5-(iodomethyl)-2-pyrrolidinone (3), generated at -20 deg C, undergoes an annulation reaction with unsaturated esters (but not sulfones), leading to pyrrolizidine derivatives.
- Knapp, Spencer,Levorse, Anthony T.
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p. 4006 - 4014
(2007/10/02)
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- INTRAMOLECULAR DIELS-ALDER CYCLOADDITIONS OF VINYLKETENIMINES. A CONVERGENT ROUTE TO CARBAZOLES AND PYRIDOCARBAZOLE ALKALOIDS
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The intramolecular Diels-Alder cycloaddition of acetylenic vinylketenimines is the key step of a highly convergent synthesis of carbazoles.A facile synthesis of N-methyl-tetrahydroellipticine has been completed in five isolated steps from N-methyl piperidone.
- Differding, Edmond,Ghosez, Leon
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p. 1647 - 1650
(2007/10/02)
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- 2-Oxocephems and 2-acetylpenems - Selective Formation in an Intramolecular Wittig Reaction
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Selective formation - in intramolecular Wittig condensations - of the 2-oxocephem-4-carboxylate 8a and of the 2-acetylpenem-3-carboxylate 9, respectively, was observed as a consequence of different carbonyl reactivities in two homologous α-oxoacylthio groupings.Free, racemic and 7-unsubstituted 2-oxocephem-4-carboxylic acid (10) was prepared from 8a for biological testing.Attempts to prepare the free 2-acetylpenem-3-carboxylic acid from 9 failed, probably due to the high lability of the β-lactam system.
- Ernest, Ivan,Main, Alan J.,Woodward, Robert B.
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p. 1303 - 1311
(2007/10/02)
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