- Construction of azacycles by intramolecular amination of organoboronates and organobis(boronates)
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Intramolecular amination of organoboronates occurs with a 1,2-metalate shift of an aminoboron ate complex to form azetidines, pyrrolidines, and piperidines. Bis(boronates) undergo site-selective amination to form boronate-containing azacycles. Enantiomerically enriched azacycles are formed with high stereospecificity.
- Xu, Peilin,Zhang, Mingkai,Ingoglia, Bryan,Allais, Christophe,Dechert-Schmitt, Anne-Marie R.,Singer, Robert A.,Morken, James P.
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p. 3379 - 3383
(2021/05/10)
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- O-benzoylhydroxylamines as alkyl nitrene precursors: Synthesis of saturated N-heterocycles from primary amines
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We introduce O-benzoylhydroxylamines as competent alkyl nitrene precursors. The combination of readily available, stable substrates and a proficient rhodium catalyst provides a straightforward means for the construction of various pyrrolidine rings from the corresponding primary amines. Preliminary mechanistic investigation suggests that the structure of the nitrene precursor plays a role in determining the nature of the resulting reactive intermediate.
- Noda, Hidetoshi,Asada, Yasuko,Shibasaki, Masakatsu
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supporting information
p. 8769 - 8773
(2020/10/12)
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- Basicities and Nucleophilicities of Pyrrolidines and Imidazolidinones Used as Organocatalysts
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The Br?nsted basicities pKaH (i.e., pKa of the conjugate acids) of 32 pyrrolidines and imidazolidinones, commonly used in organocatalytic reactions, have been determined photometrically in acetonitrile solution using CH acids as indicators. Most investigated pyrrolidines have basicities in the range 16 aH aH aH 12.6) and the 2-imidazoliummethyl-substituted pyrrolidine A21 (pKaH 11.1) are outside the typical range for pyrrolidines with basicities comparable to those of imidazolidinones. Kinetics of the reactions of these 32 organocatalysts with benzhydrylium ions (Ar2CH+) and structurally related quinone methides, common reference electrophiles for quantifying nucleophilic reactivities, have been measured photometrically. Most reactions followed second-order kinetics, first order in amine and first order in electrophile. More complex kinetics were observed for the reactions of imidazolidinones and several pyrrolidines carrying bulky 2-substituents, due to reversibility of the initial attack of the amines at the electrophiles followed by rate-determining deprotonation of the intermediate ammonium ions. In the presence of 2,4,6-collidine or 2,6-di-tert-butyl-4-methyl-pyridine, the deprotonation of the initial adducts became faster, which allowed the rate of the attack of the amines at the electrophiles to be determined. The resulting second-order rate constants k2 followed the correlation log?k2(20 °C) = sN(N + E), where electrophiles are characterized by one parameter (E) and nucleophiles are characterized by the two solvent-dependent parameters N and sN. In this way, the organocatalysts A1-A32 were integrated in our comprehensive nucleophilicity scale, which compares n-, -, and σ-nucleophiles. The nucleophilic reactivities of the title compounds correlate only poorly with their Br?nsted basicities.
- An, Feng,Maji, Biplab,Min, Elizabeth,Ofial, Armin R.,Mayr, Herbert
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supporting information
p. 1526 - 1547
(2020/02/04)
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- α-Functionalization of Cyclic Secondary Amines: Lewis Acid Promoted Addition of Organometallics to Transient Imines
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Cyclic imines, generated in situ from their corresponding N-lithiated amines and a ketone hydride acceptor, undergo reactions with a range of organometallic nucleophiles to generate α-functionalized amines in a single operation. Activation of the transient imines by Lewis acids that are compatible with the presence of lithium alkoxides was found to be crucial to accommodate a broad range of nucleophiles including lithium acetylides, Grignard reagents, and aryllithiums with attenuated reactivities.
- Paul, Anirudra,Seidel, Daniel
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supporting information
p. 8778 - 8782
(2019/06/07)
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- Tf2O-Promoted Intramolecular Schmidt Reaction of the ω-Azido Carboxylic Acids
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A designed Tf2O-promoted intramolecular Schmidt reaction of 2-substituted ω-azido carboxylic acids was demonstrated. Tf2O was used as an activation reagent for the carboxylic acid, and ω-azido anhydride was in situ generated, releasing a molecular TfOH, which acted as an acid promoter for the Schmidt process. A series of 2-substituted pyrrolidines was produced and acetylated for better purification. The strategy was also efficient for conversion of a 4-substituted ω-azido carboxylic acid to the tricyclic lactam.
- Wang, Xue-Juan,Su, Yan,Li, Rui,Gu, Peiming
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p. 5816 - 5824
(2018/05/14)
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- Enantioselective synthesis of amines by combining photoredox and enzymatic catalysis in a cyclic reaction network
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Visible light-driven reduction of imines to enantioenriched amines in aqueous solution is demonstrated for the first time. Excitation of a new water-soluble variant of the widely used [Ir(ppy)3] (ppy = 2-phenylpyridine) photosensitizer in the p
- Guo, Xingwei,Okamoto, Yasunori,Schreier, Mirjam R.,Ward, Thomas R.,Wenger, Oliver S.
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p. 5052 - 5056
(2018/06/12)
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- Redox-Triggered α-C-H Functionalization of Pyrrolidines: Synthesis of Unsymmetrically 2,5-Disubstituted Pyrrolidines
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By using o-benzoquinone as an internal oxidant, the regio- and diastereoselective functionalization of the secondary over the tertiary α-C-H bond of 2-substituted pyrrolidines is first realized. Subsequent intermolecular addition of a nucleophile to the g
- Cheng, Yong-Feng,Rong, Hao-Jie,Yi, Cheng-Bo,Yao, Jun-Jun,Qu, Jin
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supporting information
p. 4758 - 4761
(2015/10/12)
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- Catalytic olefin hydroamination with aminium radical cations: A photoredox method for direct C-N bond formation
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While olefin amination with aminium radical cations is a classical method for C-N bond formation, catalytic variants that utilize simple 2° amine precursors remain largely undeveloped. Herein we report a new visible-light photoredox protocol for the intramolecular anti-Markovnikov hydroamination of aryl olefins that proceeds through catalytically generated aminium radical intermediates. Mechanistic studies are consistent with a process involving amine oxidation via electron transfer, turnover-limiting C-N bond formation, and a second electron transfer step to reduce a carbon-centered radical, rendering the overall process redox-neutral. A range of structurally diverse N-aryl heterocycles can be prepared in good to excellent yields under conditions significantly milder than those required by conventional aminium-based protocols.
- Musacchio, Andrew J.,Nguyen, Lucas Q.,Beard, G. Hudson,Knowles, Robert R.
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p. 12217 - 12220
(2014/12/09)
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- Synthesis of 2-substituted pyrrolidines from nitriles
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A novel and synthetically facile production of 2-substituted pyrrolidines from commercially available nitriles is reported herein. This methodology is operationally simple, and only requires the use of an extraction and a single chromatographic purificati
- Ramachandran, P. Veeraraghavan,Mitsuhashi, Wataru,Nicponski, Daniel R.
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p. 5001 - 5003
(2013/08/28)
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- HETEROCYCLIC COMPOUNDS AND METHODS FOR THEIR USE
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The present invention relates to heterocyclic compounds useful for antagonising angiotensin II Type 2 (AT2) receptor. More particularly the invention relates to pyrrolidine and azetidine compounds, compositions containing them and their use in methods of treating or preventing disorders or diseases associated with AT2 receptor function including neuropathic pain, inflammatory pain, conditions associated with neuronal hypersensitivity, impaired nerve conduction velocity, cell proliferation disorders, disorders associated with an imbalance between bone resorption and bone formation and disorders associated with aberrant nerve regeneration.
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Page/Page column 95; 96
(2013/07/19)
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- 2-(CYCLIC AMINO)-PYRIMIDONE DERIVATIVES AS TPK1 INHIBITORS
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A compound represented by the formula (I), an optically active isomer thereof, or a pharmaceutical acceptable salt thereof (I) wherein R2 represents a hydrogen or the like; R3 represents methyl group or the like; R20 represents a halogen atom or the like; q represents an integer of 0 to 3; Z represent nitrogen atom, CH, or the like; R4 represents hydrogen or the like; R5 represents hydrogen or the like; R6 represents a substituted alkyloxy and the like; p represents an integer of 0 to 3; X represents bond, CH2, oxygen atom, NH, or the like; any one or more of R5 and R6, R5 and R4, R6 and R4, X and R5, X and R4, X and R6, and R6 and R6 may combine to each other to form a ring, which is used for preventive and/or therapeutic treatment of a disease caused by tau protein kinase 1 hyperactivity such as a neurodegenerative diseases (e.g. Alzheimer disease).
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Page/Page column 218; 219
(2008/06/13)
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- Bis(phosphinimino)methanide rare earth amides: Synthesis, structure, and catalysis of hydroamination/cyclization, hydrosilylation, and sequential hydroamination/hydrosilylation
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A series of yttrium and lanthanide amido complexes [Ln{N-(SiHMe 2)2}2{CH(PPh2NSiMe3) 2}] (Ln = Y, La, Sm, Ho, Lu) were synthesized by three different pathways. The title compounds can be obtained either from [Ln{N(SiHMe 2)2}3(thf)2] and [CH 2(PPh2NSiMe3)2] or from KN-(SiHMe2)2 and [Ln(CH(PPh2NSiMe 3)2}-Cl2]2, while in a third approach the lanthanum compound was synthesized in a one-pot reaction starting from K{CH(PPh2NSiMe3)2}, LaCl3, and KN-(SiHMe2)2. All the complexes have been characterized by single-crystal X-ray diffraction. The new complexes, [Ln{N(SiHMe 2)2}2{CH(PPh2NSiMe3) 2}], were used as catalysts for hydroamination/cyclization and hydrosilylation reactions. A clear dependence of the reaction rate on the ionic radius of the center metal was observed, showing the lanthanum compound to be the most active one in both reactions. Furthermore, a combination of both reactions - a sequential hydroamination/hydrosilylation reaction - was also investigated.
- Rastaetter, Marcus,Zulys, Agustino,Roesky, Peter W.
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p. 3606 - 3616
(2008/02/10)
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- Pd(OAc)2-catalyzed carbonylation of amines
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A phosphine-free catalytic system [Pd(OAc)2-Cu(OAc) 2-air] induced a substrate-specific carbonylation of amines in boiling toluene under CO gas (1 atm). Symmetrical N,N′-dialkylureas were obtained by the carbonylation of primary amines. N,N,N′-Trialkylureas were selectively formed by addition of a secondary amine to the above reaction vessel. Secondary amines did not give tetraalkylureas. However, dialkylamines with a phenyl group on their alkyl chains, such as N-monoalkylated benzylic amine or phenethylamine derivatives, underwent a direct aromatic carbonylation to afford five- or six-membered benzolactams. In the carbonylation, the chelation effect or steric repulsion between Pd(II) and the meta-substituent in the ortho-palladation and the ring sizes of cyclopalladation products that were formed prior to carbonylation were found to generate good site selectivity and increase the reaction rate. In contrast, carbonylation of ω- arylalkylamines with a hydroxyl group gave neither ureas nor benzolactams but instead produced 1,3-oxazolidinones smoothly. Hydrochlorides of amines also underwent carbonylation to afford the corresponding amides under the conditions used. This procedure made it possible to prepare ureas of amino acid esters and N-alkylcarbamates in practical yields.
- Orito, Kazuhiko,Miyazawa, Mamoru,Nakamura, Takatoshi,Horibata, Akiyoshi,Ushito, Harumi,Nagasaki, Hideo,Yuguchi, Motoki,Yamashita, Satoshi,Yamazaki, Tetsuro,Tokuda, Masao
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p. 5951 - 5958
(2007/10/03)
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- The Cp2TiMe2-catalyzed intramolecular hydroamination/cyclization of aminoalkynes
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Cp2TiMe2 has been found to be a competent catalyst for the intramolecular hydroamination/cyclization of aminoalkynes. In the presence of 5.0 mol% Cp2TiMe2, the hydroamination reactions proceed smoothly at 100-110°C to give five- and six-membered cyclic imines within 4-6 h. After subsequent reduction performed with zinc-modified NaBH3CN at room temperature cyclic amines can be isolated in good yields.
- Bytschkov, Igor,Doye, Sven
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p. 3715 - 3718
(2007/10/03)
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- Electrophilic formamidines. Organometallic addition to 2-methoxy pyrrolidine or piperidine N-t-butyl formamidines. Formation of 2-substituted pyrrolidines and piperidines
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The title compounds were prepared by addition of Grignard reagents to methoxyformamidines 6 and 8 in ether at room temperature. Hydrolysis gives the free secondary amines, or in cases of volatile products, their thiourea derivatives.
- Gottlieb,Meyers
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p. 4723 - 4726
(2007/10/02)
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- THE PREPARATION OF "ELONGATED" NICOTINE ANALOGUES
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The preparation of four nicotine analogues having one or two additional methylene units between the N-methylpyrrolidinyl moiety and the aromatic ring are reported.Also prepared are the corresponding nornicotine and myosmine analogues.The course of the Spa
- Secor, Henry V.,Seeman, Jeffrey I.
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p. 1687 - 1698
(2007/10/02)
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- A NOVEL THREE CARBON-AMINO GRIGNARD REAGENT: ITS USE IN AN EFFICIENT PYRROLIDINE SYNTHESIS
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A novel primary amino protected Grignard reagent has been developed; 2,2,5,5-tetramethyl-1-aza-2,5-disilacyclopentane-1-propyl magnesium bromide 1a.Its usefulness is illustrated in the synthesis of 2-substituted pyrrolidines.
- Basha, Fatima Z.,DeBernardis, John F.
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p. 5271 - 5274
(2007/10/02)
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- Synthesis of Hexahydropyrroloisoquinolines - Analogs of Phenanthroindolizidine Anticancer Alkaloids
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A convenient preparative route has been developed for the synthesis of hexahydropyrroloisoquinolines involving condensation of an araldehyde with ethyl 4-nitrobutanoate followed by LAH reduction and subsequent cyclization with H2SO4 to 2-arylmethylpyrrolidines.The latter on formylation and Bischler-Napieralsky cyclization followed by NaBH4 reduction give the required pyrroloisoquinolines.Using this method, 8-methoxy-1,2,3,5,10,10a-hexahydropyrroloisoquinoline (IXa); 7,8-dimethoxy-1,2,3,5,10,10a-hexahydropyrroloisoquinoline (IXb); 7,9,10,11,11a,12-hexahydrobenzopyrroloisoquinoline (Xa); 3-methoxy-7,9,10,11,11a,12-hexahydrobenzopyrroloisoquinoline (Xb); 7,7a,8,9,10,12-hexahydrobenzopyrroloisoquinoline (XIa); 3-methoxy-7,7a,8,9,10,12-hexahydrobenzopyrroloisoquinoline (XIb) and 2,3-dimethoxy-7,7a,8,9,10,12-hexahydrobenzopyrroloisoquinoline (XIc) have been synthesized.None of these compounds has shown any noteworthy anticancer activity while few have exhibited interesting antihistaminic, β-blocking, hypertensive, antiinflammatory and antireserpine activities.
- Gaur, S. P.,Jain, Padam C.,Anand, Nitya
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