- Synthesis of 3-phenyl- and 5- phenyl- 2- pyrrolidinone via rhodium catalysed carbonylation of allylamines
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The Rh4(CO)12 catalysed reaction with CO and H2 of 1-phenyl- and 3-phenyl allylamine gives 5-phenyl- and 3-phenyl-2-pyrrolidinone respectively, in good yield. A reasonable reaction pathway of the carbonylation reaction is
- Bertozzi, Sergio,Salvadori, Piero
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Read Online
- A mechanism-based cleavage of lactam-carbamates
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Magnesium methoxide is a simple, effective and highly selective reagent for the deprotection of N-alkoxycarbonyl lactams. The cleavage occurs via six-membered ring transition states involving coordination of magnesium ion with the oxygens of the carbamate and lactam carbonyl groups.
- Wei, Zhong-Yong,Knaus, Edward E.
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Read Online
- Tropylium-promoted Ritter reactions
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The Ritter reaction used to be one of the most powerful synthetic tools to functionalize alcohols and nitriles, providing valuableN-alkyl amide products. However, this reaction has not been frequently used in modern organic synthesis due to its employment of strongly acidic and harsh reaction conditions, which often lead to complicated side reactions. Herein, we report the development of a new method using salts of the tropylium ion to promote the Ritter reaction. This method works well on a range of alcohol and nitrile substrates, giving the corresponding products in good to excellent yields. This reaction protocol is amenable to microwave and continuous flow reactors, offering an attractive opportunity for further applications in organic synthesis.
- Doan, Son H.,Hussein, Mohanad A.,Nguyen, Thanh Vinh
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supporting information
p. 8901 - 8904
(2021/09/10)
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- Highly Robust Iron Catalyst System for Intramolecular C(sp3)?H Amidation Leading to γ-Lactams
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Disclosed here is the use of an iron catalyst system for an intramolecular C?H amidation toward γ-lactam synthesis from dioxazolone precursors. (Phthalocyanine)FeIIICl was found to catalyze this cyclization with extremely high turnover numbers of up to 47 000 under mild and aerobic conditions. On the basis of experimental and computational mechanistic studies, the reaction is suggested to proceed by a stepwise radical pathway involving fast hydrogen atom abstraction followed by radical rebound. A plausible origin for the high turnover numbers along with air-compatibility is also rationalized.
- Kweon, Jeonguk,Chang, Sukbok
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supporting information
p. 2909 - 2914
(2020/12/11)
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- Direct Synthesis of Chiral NH Lactams via Ru-Catalyzed Asymmetric Reductive Amination/Cyclization Cascade of Keto Acids/Esters
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Lactams with a stereogenic center adjacent to the N atom have existed in many medicinal agents and bioactive alkaloids. Herein we report a broadly applicable synthesis of enantioenriched NH lactams through a one-pot asymmetric reductive amination/cyclization sequence of easily available keto acids/esters. Such cascade processes alleviate the demand for protecting group manipulations as well as intermediate purification. This strategy is capable of constructing enantioenriched lactams and benzo-lactams of a five-, six-, or seven-membered ring in generally high yield and with excellent enantioselectivities (up to 97% ee). Scalable and concise syntheses of key drug intermediates have further displayed the importance of this methodology.
- Shi, Yongjie,Tan, Xuefeng,Gao, Shuang,Zhang, Yao,Wang, Jingxin,Zhang, Xumu,Yin, Qin
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supporting information
p. 2707 - 2713
(2020/03/30)
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- Total syntheses of (?)-emestrin H and (?)-asteroxepin
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First total syntheses of (?)-emestrin H and (?)-asteroxepin are described. To find the appropriate protecting group on the amide nitrogen of the diketopiperazine core, we conducted model studies using a simple diketopiperazine derivative. As a result, allyloxymethyl (Allom) group was the most suitable protecting group, which tolerated Nicolaou's sulfenylation conditions, and was easily cleavable under the mild conditions using Pd(PPh3)4 and N,N-dimethylbarbituric acid leaving methylthioethers intact. The general utility of Allom group for protection of amides was studied using simple substrates. Finally, the effectiveness of Allom group was proved by the accomplishment of the first total synthesis of (?)-emestrin H. Allom group was robust enough during installation of two methylthioethers to the diketopiperazine core and easily removed at the final step. The first total synthesis of (?)-asteroxepin was also completed by acylation of (?)-emestrin H.
- Sakata, Juri,Tokuyama, Hidetoshi,Ueda, Yusuke,Umeki, Kanato
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- Tuning Triplet Energy Transfer of Hydroxamates as the Nitrene Precursor for Intramolecular C(sp3)-H Amidation
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Reported herein is the design of a photosensitization strategy to generate triplet nitrenes and its applicability for the intramolecular C-H amidation reactions. Substrate optimization by tuning physical organic parameters according to the proposed energy transfer pathway led us to identify hydroxamates as a convenient nitrene precursor. While more classical nitrene sources, representatively organic azides, were ineffective under the current photosensitization conditions, hydroxamates, which are readily available from alcohols or carboxylic acids, are highly efficient in accessing synthetically valuable 2-oxazolidinones and γ-lactams by visible light. Mechanism studies supported our working hypothesis that the energy transfer path is mainly operative.
- Chang, Sukbok,Jung, Hoimin,Keum, Hyeyun,Kweon, Jeonguk
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supporting information
p. 5811 - 5818
(2020/04/10)
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- Synthesis of Lactams via Ir-Catalyzed C-H Amidation Involving Ir-Nitrene Intermediates
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x-membered lactams were synthesized via either an amidation of sp3 C-H bonds or an electrophilic substitution of arenes via Ir-nitrene intermediates. With the employment of a readily available iridium catalyst in dichloromethane or hexafluoro-2-propanol, a wide range of lactams were synthesized in good to excellent yields with high selectivity.
- Li, Xiaoxun,Liu, Jitian,Tang, Weiping,Wang, Shuojin,Ye, Wenjing,Zheng, Junrong
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- Strategic Approach to the Metamorphosis of γ-Lactones to NH γ-Lactams via Reductive Cleavage and C-H Amidation
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A new approach has elaborated on the conversion of γ-lactones to the corresponding NH γ-lactams that can serve as γ-lactone bioisosteres. This approach consists of reductive C-O cleavage and an Ir-catalyzed C-H amidation, offering a powerful synthetic tool for accessing a wide range of valuable NH γ-lactam building blocks starting from γ-lactones. The synthetic utility was further demonstrated by the late-stage transformation of complex bioactive molecules and the asymmetric transformation.
- Jung, Hoi-Yun,Chang, Sukbok,Hong, Sungwoo
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p. 7099 - 7103
(2019/09/07)
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- Site-Specific Synthesis of β-Fluorinated γ-Butyrolactams via Decarboxylative Fluorination of β-Carboxyl-γ-Butyrolactams
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Monofluorinated cyclic nitrogen-containing compounds are synthetically useful scaffolds in organic synthesis and medicinal applications. In this report, AgNO3 mediated decarboxylative fluorination of β-carboxyl-γ-butyrolactams using Selectfluor as a fluorine source was described to achieve a site-specific synthesis of β-fluorinated γ-butyrolactams.
- Phae-nok, Supasorn,Pohmakotr, Manat,Kuhakarn, Chutima,Reutrakul, Vichai,Soorukram, Darunee
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p. 4710 - 4720
(2019/08/01)
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- Method for synthesizing lactam derivative without catalyst
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The invention discloses a simple synthesis method for a lactam derivative. The method comprises the step that with formamide as an amine source and a hydrogen donor (hydrolyzed to produce formic acid)and keto acid as raw materials, the lactam derivative is easily synthesized through a cycloamination reaction without a solvent or a catalyst. Compared with previous reports, the time required for the reaction is greatly shortened, the selectivity is remarkably improved, the conversion rate of the keto acid derivative is 99%, and the yield of the lactam derivative can reach 70-94%.
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Paragraph 0026-0029
(2019/07/10)
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- Synthetic Utility of N-Benzoyloxyamides as an Alternative Precursor of Acylnitrenoids for γ-Lactam Formation
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Described herein is the development of a new entry of acylnitrenoid precursors for γ-lactam synthesis via an intramolecular C-H amidation reaction. Upon Ir catalysis, N-benzoyloxyamides serve as efficient substrates to afford 5-membered amides. Mechanistic studies revealed that the generation of a putative Ir-carbonylnitrenoid via N-O bond cleavage is facilitated by the chelation of countercations. This protocol offers a convenient and step-economic route to γ-lactams starting from the corresponding carboxylic acids.
- Huh, Soohee,Hong, Seung Youn,Chang, Sukbok
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supporting information
p. 2808 - 2812
(2019/04/17)
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- Ruthenium(II)-Catalyzed Enantioselective ?-Lactams Formation by Intramolecular C-H Amidation of 1,4,2-Dioxazol-5-Ones
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We report the Ru-Catalyzed enantioselective annulation of 1,4,2-Dioxazol-5-Ones to furnish ?-Lactams in up to 97% yield and 98% ee via intramolecular carbonylnitrene C-H insertion. By employing chiral diphenylethylene diamine (dpen) as ligands bearing electron-Withdrawing arylsulfonyl substituents, the reactions occur with remarkable chemo- A nd enantioselectivities; the competing Curtius-Type rearrangement was largely suppressed. Enantioselective nitrene insertion to allylic/propargylic C-H bonds was also achieved with remarkable tolerance to the Ca?C and Ca‰iC bonds.
- Xing, Qi,Chan, Chun-Ming,Yeung, Yiu-Wai,Yu, Wing-Yiu
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- Ruthenium(II)-Catalyzed Enantioselective γ-Lactams Formation by Intramolecular C-H Amidation of 1,4,2-Dioxazol-5-ones
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We report the Ru-catalyzed enantioselective annulation of 1,4,2-dioxazol-5-ones to furnish γ-lactams in up to 97% yield and 98% ee via intramolecular carbonylnitrene C - H insertion. By employing chiral diphenylethylene diamine (dpen) as ligands bearing electron-withdrawing arylsulfonyl substituents, the reactions occur with remarkable chemo- and enantioselectivities; the competing Curtius-type rearrangement was largely suppressed. Enantioselective nitrene insertion to allylic/propargylic C - H bonds was also achieved with remarkable tolerance to the C=C and C=C bonds.
- Xing, Qi,Chan, Chun-Ming,Yeung, Yiu-Wai,Yu, Wing-Yiu
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p. 3849 - 3853
(2019/04/25)
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- Harnessing Secondary Coordination Sphere Interactions That Enable the Selective Amidation of Benzylic C-H Bonds
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Engineering site-selectivity is highly desirable especially in C-H functionalization reactions. We report a new catalyst platform that is highly selective for the amidation of benzylic C-H bonds controlled by π-πinteractions in the secondary coordination sphere. Mechanistic understanding of the previously developed iridium catalysts that showed poor regioselectivity gave rise to the recognition that the π-cloud of an aromatic fragment on the substrate can act as a formal directing group through an attractive noncovalent interaction with the bidentate ligand of the catalyst. On the basis of this mechanism-driven strategy, we developed a cationic (ν5-C5H5)Ru(II) catalyst with a neutral polypyridyl ligand to obtain record-setting benzylic selectivity in an intramolecular C-H lactamization in the presence of tertiary C-H bonds at the same distance. Experimental and computational techniques were integrated to identify the origin of this unprecedented benzylic selectivity, and robust linear free energy relationship between solvent polarity index and the measured site-selectivity was found to clearly corroborate that the solvophobic effect drives the selectivity. Generality of the reaction scope and applicability toward versatile γ-lactam synthesis were demonstrated.
- Jung, Hoimin,Schrader, Malte,Kim, Dongwook,Baik, Mu-Hyun,Park, Yoonsu,Chang, Sukbok
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supporting information
p. 15356 - 15366
(2019/10/22)
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- A Facile Direct Route to N-(Un)substituted Lactams by Cycloamination of Oxocarboxylic Acids without External Hydrogen
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Lactams are privileged in bioactive natural products and pharmaceutical agents and widely featured in functional materials. This study presents a novel versatile approach to the direct synthesis of lactams from oxocarboxylic acids without catalyst or external hydrogen. The method involves the in situ release of formic acid from formamides induced by water to facilitate efficient cycloamination. Water also suppresses the formation of byproducts. This unconventional pathway is elucidated by a combination of model experiments and density functional theory calculations, whereby cyclic imines (5-methyl-3,4-dihydro-2-pyrrolone and its tautomeric structures) are found to be favorable intermediates toward lactam formation, in contrast to the conventional approach encompassing cascade reductive amination and cyclization. This sustainable and simple protocol is broadly applicable for the efficient production of various N-unsubstituted and N-substituted lactams.
- Li, Hu,Wu, Hongguo,Zhang, Heng,Su, Yaqiong,Yang, Song,Hensen, Emiel J. M.
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p. 3778 - 3784
(2019/08/07)
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- Conversion of γ- and δ-Keto Esters into Optically Active Lactams. Transaminases in Cascade Processes
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A one-pot two-step enzymatic strategy has been designed for the production of optically active γ- and δ-lactams in aqueous medium under mild conditions. The approach is based on the biotransamination of ethyl or methyl keto esters bearing different alkyl or aryl substitution patterns at α-position to the ketone functionality. In this manner, the keto esters were transformed into the corresponding amino esters with excellent conversions, which underwent spontaneous cyclisation in the reaction medium without addition of external reagents. Depending on the transaminase selectivity, both lactam enantiomers can be obtained, so initial enzyme screenings were performed using commercially available and made in house enzymes. Reaction conditions were optimised focusing on the substrate concentration, temperature and ratio of amine donor vs acceptor. Thus, ten γ- and δ-lactams were obtained in good to high isolated yields (70–90%) and excellent selectivities (94–99%) after one or two days at 30 or 45 °C. (Figure presented.).
- Mourelle-Insua, ángela,Zampieri, Luiz Arthur,Lavandera, Iván,Gotor-Fernández, Vicente
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p. 686 - 695
(2018/02/21)
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- Visible-Light-Mediated Remote γ-C(sp3)-H Functionalization of Alkylimidates: Synthesis of 4-Iodo-3,4-dihydropyrrole Derivatives
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An efficient and environmentally friendly synthetic approach toward functionalized dihydropyrrole derivatives is reported. The developed protocol proceeds via chemoselective intramolecular N-C bond formation of alkylimidates through 1,5-hydrogen atom transfer from in situ generated imidate N-radicals. The major advantage of this designed strategy lies in the choice of starting materials, mild reaction conditions, high chemo- and diastereoselectivity, clean source of energy, and good functional group tolerance. Further, 4-iododihydropyrroles could be easily transformed into a variety of useful derivatives.
- Kumar, Yogesh,Jaiswal, Yogesh,Kumar, Amit
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p. 4964 - 4969
(2018/08/24)
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- Selective formation of γ-lactams via C-H amidation enabled by tailored iridium catalysts
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Intramolecular insertion of met al nitrenes into carbon-hydrogen bonds to form γ-lactam rings has traditionally been hindered by competing isocyanate formation. We report the application of theory and mechanism studies to optimize a class of pentamethylcyclopentadienyl iridium(III) catalysts for suppression of this competing pathway. Modulation of the stereoelectronic properties of the auxiliary bidentate ligands to be more electron-donating was suggested by density functional theory calculations to lower the C-H insertion barrier favoring the desired reaction. These catalysts transform a wide range of 1,4,2-dioxazol-5-ones, carbonylnitrene precursors easily accessible from carboxylic acids, into the corresponding γ-lactams via sp3 and sp2 C-H amidation with exceptional selectivity. The power of this method was further demonstrated by the successful late-stage functionalization of amino acid derivatives and other bioactive molecules.
- Hong, Seung Youn,Park, Yoonsu,Hwang, Yeongyu,Kim, Yeong Bum,Baik, Mu-Hyun,Chang, Sukbok
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p. 1016 - 1021
(2018/03/09)
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- α-Alkylation of ketimines using visible light photoredox catalysis
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A novel α-alkylation of N-diphenylphosphinoyl ketimines with α-bromocarbonyl compounds has been accomplished using visible light photoredox catalysis. The reaction proceeds under remarkably mild conditions: at 35 °C, in 20 hours, under blue light irradiation (1 W), in the presence of a tertiary amine and catalytic amounts of Ru- and Ni-based complexes. Chemoselective transformation of the products provides access to 1,4-dicarbonyl compounds, protected GABA analogues and γ-lactams.
- Franchino, Allegra,Rinaldi, Antonia,Dixon, Darren J.
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p. 43655 - 43659
(2017/09/22)
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- Electroreductive coupling of aromatic ketones, aldehydes, and aldimines with α,β-unsaturated esters: Synthesis of 5-aryl substituted γ-butyrolactones and lactams
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The electroreductive intermolecular coupling of aromatic ketones and aldehydes with α,β-unsaturated esters in the presence of TMSCl gave the adducts as γ-trimethylsiloxy esters. The detrimethylsilylation of the adducts with TBAF afforded 5-aryl substituted γ-butyrolactones. The electroreductive coupling of N-(4-methoxyphenyl)-1-arylmethaneimines with methyl acrylate in the presence of TMSCl gave the adducts as methyl 4-aryl-4-((4-methoxyphenyl)amino)butanoates. The adducts were transformed to 5-aryl-γ-butyrolactams by cyclization with NaH and subsequent oxidation with CAN. (±)-Norcotinine was prepared from nicotinaldehyde by this method. The electroreductive coupling of aromatic ketones and aldimines with acrylonitrile in the presence of TMSCl gave 4-aryl-4-(trimethylsiloxy)butanenitriles and 4-aryl-4-((4-methoxyphenyl)amino)butanenitriles, respectively.
- Kise, Naoki,Hamada, Yusuke,Sakurai, Toshihiko
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p. 1143 - 1156
(2017/02/18)
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- Synthesis of γ-Lactams by Mild, o-Benzoquinone-Induced Oxidation of Pyrrolidines Containing Oxidation-Sensitive Functional Groups
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The late-stage oxidation of substituted pyrrolidines offers good flexibility for the construction of γ-lactam libraries, and especially in recent years the methods for functionalization of pyrrolidine have been available. We reported a new strategy for oxidation of pyrrolidines to γ-lactams: reaction of pyrrolidine with an o-benzoquinone gives an N,O-acetal by direct oxidation of the α-C-H bond of the pyrrolidine ring, and then the N,O-acetal is further oxidized by the o-benzoquinone to the γ-lactam. Because the first oxidation occurs selectively at the α-C-H of the pyrrolidine ring, oxidation-sensitive functional groups (allyl-, vinyl-, hydroxyl-, and amino groups) on pyrrolidine ring are unaffected. The synthetic utility of this novel method was demonstrated by the facile syntheses of (S)-vigabatrin and two analogues.
- Rong, Hao-Jie,Cheng, Yong-Feng,Liu, Fan-Fan,Ren, Shu-Jian,Qu, Jin
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p. 532 - 540
(2017/04/26)
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- TRICYCLIC MODULATORS OF TNF SIGNALING
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The invention provides tricyclic heterocyclic compounds, pharmaceutically acceptable salts, prodrugs, biologically active metabolites, stereoisomers and isomers thereof wherein the variables are defined herein. The compounds of the invention may be useful for treating immunological and oncological conditions.
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Page/Page column 153
(2016/11/02)
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- FUSED TRICYCLIC BENZIMIDAZOLES DERIVATIVES AS MODULATORS OF TNF ACTIVITY
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A series of tricyclic benzimidazole derivatives, in particular dihydro-1H- imidazo [1,2-a]benzimidazo le, dihydro-1H-pyrrolo [1,2-a]benzimidazo le, dihydro-1H- pyrazino[1,2-a]benzimidazole, dihydro-1H-[1,4]oxazino[4,3-a]benzimidazole and dihydrothiazolo[3,4-a]benzimidazolem, and analogues thereof, being potent modulators of human TNFa activity, are accordingly of benefit in the treatment and/or prevention of various human ailments, including autoimmune and inflammatory disorders; neurological and neurodegenerative disorders; pain and nociceptive disorders; cardiovascular disorders; metabolic disorders; ocular disorders; and oncological disorders.
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Page/Page column 111
(2015/06/25)
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- Carbon-carbon bond formations at the benzylic positions of N-benzylxanthone imines and N-benzyldi-1-naphthyl ketone imine
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Two N-benzyl imines are designed to allow for carbon-carbon bond formations at the aminated benzylic positions. Direct benzylic arylation reactions of N-benzylxanthone imine with aryl chlorides proceed under palladium catalysis in the presence of cesium hydroxide, yielding the corresponding benzhydrylamine derivatives. Alkylation reactions of N-benzyldi-1-naphthyl ketone imine with alkyl halides in the presence of potassium tert-butoxide afford the corresponding 1-phenylalkylamines in high yields. Conjugate addition of N-benzyldi-1-naphthyl ketone imine is also described.
- Niwa, Takashi,Suehiro, Takafumi,Yorimitsu, Hideki,Oshima, Koichiro
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experimental part
p. 5125 - 5131
(2009/11/30)
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- Synthesis and absolute configuration of novel N,O-psiconucleosides using (R)-N-phenylpantolactam as a resolution agent
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(Chemical Equation Presented) A series of novel N,O-psiconucleosides has been prepared in both enantiomeric forms by resolution of an advanced racemic synthetic intermediate using (R)-N-phenylpantolactam as a chiral resolution agent. The absolute configur
- Camps, Pelayo,Gomez, Tania,Munoz-Torrero, Diego,Rull, Jordi,Sanchez, Laura,Boschi, Francesca,Comes-Franchini, Mauro,Ricci, Alfredo,Calvet, Teresa,Font-Bardia, Merce,De Clercq, Erik,Naesens, Lieve
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p. 6657 - 6665
(2008/12/23)
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- 2-hetaryl-3,4-dihydro-2H-pyrrole derivatives
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The invention relates to novel 2-hetaryl-3,4-dihydro-2H-pyrrole derivatives of the formula (I) in which Hetaryl represents substituted heterocyclyls and Ar represents substituted phenyl, to a plurality of processes for their preparation and to their use a
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- 2-(2-chlorophenyl)-3,4-dihydro-2h-pyrrol derivatives
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The invention relates to novel 2-(2-chlorophenyl)-3,4-dihydro-2H-pyrrole derivatives of the formula (I) in which Ar represents substituted phenyl, to a plurality of processes for their preparation and to their use as pesticides.
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- Intramolecular Cyclization of Acyl Radicals onto the Azido Group: A New Radical Approach to Cyclized Lactams
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(Equation Presented) Reagents: i, Bu3SnH/AlBN; ii, (TMS)3SiH/AlBN. Aryl- and alkyl-derived azidoacyl radicals, generated from thiolesters by intramolecular homolytic substitution at the sulfur, can undergo five- and six-membered cyclization onto the azido moiety to give cyclized lactams.
- Benati, Luisa,Leardini, Rino,Minozzi, Matteo,Nanni, Daniele,Spagnolo, Piero,Strazzari, Samantha,Zanardi, Giuseppe
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p. 3079 - 3081
(2007/10/03)
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- Chemical and microsomal oxidation of tertiary amides: Regio- and stereoselective aspects
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The conformationally restricted tertiary amides N-methyl-2-pyrrolidone 6, N-methyl-2-piperidone 7 and N-methyl-ε-caprolactam 8 were oxidised by 5,10,15,20-tetraphenylporphyrinatoiron(III) chloride/tert-butyl hydroperoxide (TPPFe/ButOOH) and by phenobarbital-induced rat liver microsomes. The products were the N-demethylated lactams together with the analogous N-methylimides and norimides. For the TPPFe/ButOOH reaction ring oxidation is preferred to N-demethylation, paralleling the relative stabilities of the corresponding intermediate carbon-centred radicals as calculated by the AM1 semi-empirical method. In contrast, the microsomal reaction of the N-methyllactams strongly favours N-demethylation, demonstrating that hydrogen atom abstraction from the alkyl group Z to the amide carbonyl oxygen atom is preferred. The chiral tertiary amides N-methyl-N-(1-phenylethyl)benzamide 9 and N-methyl-5-phenyl-2-pyrrolidone 10 were also oxidised by TPPFe/ButOOH and by phenobarbital-induced rat liver microsomes. Using TPPFe/ButOOH, loss of the secondary alkyl group of 9 is preferred by a factor of ca. 6. Similarly, ring oxidation of 10 is favoured over demethylation by a factor of 9. For the microsomal reaction of (R)-9 dealkylation is preferred over demethylation by a factor of 1.7, whereas for (S)-9 demethylation is favoured by a factor of 1.25. For the microsomal reaction of (R)-10 and (S)-10 ring oxidation at the 5-position of the pyrrolidone ring is preferred over demethylation by factors of ca. 4 and 9 for the two isomers, respectively, and the (S)-enantiomer undergoes ring oxidation 2-3 times more readily than the (R)-enantiomer. For both 9 and 10 there is negligible stereochemical influence of the chiral centre upon the N-demethylation reaction. The results show that the stereochemical preference of the microsomal N-dealkylation reaction is modest.
- Iley, Jim,Tolando, Roberto,Constantino, Luis
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p. 1299 - 1305
(2007/10/03)
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- Cyclic imines as pesticides
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The invention relates to novel cyclic imines of the formula (I) in which Ar1and Ar2each represent substituted phenyl and n represents 1, to a process for their preparation and to their use as pesticides.
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- Stereoselective alkylation of N-Boc-2-pyrrolidinones and N-Boc-2- piperidinones. Synthesis and characterization of disubstituted lactams
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Alkylation of enolates of monosubstituted N-Boc lactams 4-6 afforded trans-disubstituted lactams as the major isomer. In the pyrrolidinone series, 1,3-induction seems to be ruled by steric interactions and the diastereoselection is low for the alkylation of enolates with small substituents at C-5 (e.g., Me) and methyl iodide. The trans selectivity improves with bulkier substituents at C-2 and/or bulkier electrophiles. The formation of 3,6-trans-disubstituted piperidinones benefits from the axial orientation of the substituent at C-2 due to the A strain with the N-Boc group and excellent trans preference is observed even in the alkylation of the lithium enolate of N-Boc-6-methyl piperidinone with methyl iodide.
- Maldaner, Adriano O.,Pilli, Ronaldo A.
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p. 13321 - 13332
(2007/10/03)
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- Phenyl-Substituted Analogues of Oxotremorine as Muscarinic Antagonists
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A series of phenyl-substituted analogues of the muscarinic agent oxotremorine (1) have been prepared.The new compounds (3b-11b and 9c) were assayed for antimuscarinic activity on the isolated guinea pig ileum and in intact mice.They were also evaluated for ability to inhibit the binding of the muscarinic antagonist (-)--N-methylscopolamine to homogenates of the rat cerebral cortex.The phenyl-substituted derivatives were devoid of intrinsic muscarinic activity.Instead, they behaved as competitive muscarinic antagonists in these assays with similar or lower affinity for muscarinic receptors than the corresponding methyl-substituted analogues.The succinimide (8b) and the pyrrolidone (3b) derivatives of 1 substituted with a phenyl group at position 1 of the bytynyl chain showed the highest antimuscarinic potency with dissociation constants (KD) of 0.10 and 0.20 μM, respectively, in the ileum assay.The phenyl-substituted analogues showed an approximately 10-fold lower in vivo antimuscarinic potency than their corresponding methyl-substituted position isomers.A correlation was observed between in vitro and in vivo potency within subsets consisting of methyl- and phenyl-substituted derivatives.
- Nilsson, Bjoern M.,Vargas, Hugo M.,Ringdahl, Bjoern,Hacksell, Uli
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p. 285 - 294
(2007/10/02)
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- Electroreductive Coupling of Aromatic Imines with Electrophiles in the Presence of Chlorotrimethylsilane
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Electroreduction of aromatic imines in the presence of electrophiles gave the corresponding inter- and intramolecular coupling products when the reaction was carried out with the use of chlorotrimethylsilane (CTMS) as the trapping agent of an anion interm
- Shono, Tatsuya,Kise, Naoki,Kunimi, Nobutaka,Nomura, Ryoji
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p. 2191 - 2194
(2007/10/02)
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- Decarboxylation of pyroglutamic acids with P2O5/CH3SO:3H: A general synthesis of 5-aryl-2-pyrrolidinones
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Treatment of pyroglutamic acids with acyl-activating reagents (P2O5/CH3SO3H, PPE....), possibly in the presence of triethylamine, yields acyl iminium salts, that can react in-situ with aromatic compounds to give
- Rigo,Fasseur,Cherepy,Couturier
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p. 7057 - 7060
(2007/10/02)
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- Conformationally restricted analogues of the muscarinic agent N-methyl-N-(1-methyl-4-pyrrolidono-2-butynyl)acetamide
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Conformationally restricted analogues of the selective partial muscarinic agonist N-methyl-N-(1-methyl-4-pyrrolidono-2-butynyl)acetamide (BM 5; 2) were synthesized. The compounds were tested for muscarinic and antimuscarinic activity in the isolated guine
- Lundkvist,Ringdahl,Hacksell
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p. 863 - 869
(2007/10/02)
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- Selective Reduction of Pyridazin-3-ones and Ring Contraction to Pyrrolidin-2-ones and 3-Pyrrolin-2-ones
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Reduction of pyridazin-3-ones (1a-d) with zinc dust in acetic acid affords selectively 4,5-dihydropyridazin-3-ones (2a-d), but N(2)-substituted (1) react further with excess of zinc to give equal amounts of pyrrolidin-2-ones (3) and 3-pyrrolin-2-ones (4).
- Brown, George R.,Foubister, Alan J.,Wright, Brian
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p. 1373 - 1374
(2007/10/02)
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- An Efficient and General Synthesis of 5-Substituted Pyrrolidinones
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2-Pyrrolidinone derivatives are widespread materials of considerable laboratory and commercial importance.In spite of this, there is no generally useful synthesis of either symmetrically or unsymmetrically 5,5-disubstituted derivatives.This is particularl
- Miller, R. D.,Goelitz, P.
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p. 1616 - 1618
(2007/10/02)
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