- Lithium perchlorate mediated three-component preparation of primaryaminoesters
-
A three-component reaction between an aldehyde, metallated hexamethyldisilazane and a functionalized organozinc compound proceeded smoothly in the presence of LiClO4 in diethyl ether to afford primary amino esters in good yields.
- Saidi, Mohammad R.,Azizi, Najmoddin
-
-
Read Online
- Photoactive spatial proximity probes for binding pairs with epigenetic marks
-
A new strategy for encoding polypeptide libraries with photolabile tags is developed. The photoassisted assay, based on conditional release of encoding tags only from bound pairs, can differentiate between peptides which have minor differences in a form o
- Ezhov, Roman N.,Metzel, Greg A.,Mukhina, Olga A.,Musselman, Catherine A.,Kutateladze, Tatiana G.,Gustafson, Tiffany P.,Kutateladze, Andrei G.
-
-
Read Online
- Chiral phosphoric acid catalyzed enantioselective [4 + 2] cycloaddition reaction of α-fluorostyrenes with imines
-
An enantioselective [4 + 2] cycloaddition reaction of α-fluorostyrenes with N-benzoyl imines was demonstrated using a chiral phosphoric acid catalyst. Cycloaddition products having fluorine functionality were formed in high yields with excellent diastereo
- Terada, Masahiro,Kikuchi, Jun,Ye, Haiting
-
supporting information
p. 8957 - 8961
(2020/12/02)
-
- Direct and practical Gilman-Speeter synthesis of 3,4-trisubstituted β-lactams via the Thorpe-Ingold effect
-
A highly efficient Gilman-Speeter synthesis of 3,4-trisubstituted β-lactams possessing a 4-aryl substituent is described, employing a direct, uncatalyzed Mannich reaction between TMS imines and TMS ketene acetals. The process avoids cryogenic conditions, making it more amenable to process-scale use than related methods for β-lactam synthesis. A Gilman-Speeter diastereoselective version using a sulfinyl imine and leading to homochiral sulfinyl β-aminoester is also presented.
- Panagiotou, Maria,Demos, Vasileios,Magriotis, Plato Α.
-
supporting information
(2020/09/09)
-
- Synthesis of Multifunctional Spirocyclic Azetidines and Their Application in Drug Discovery
-
The synthesis of multifunctional spirocycles was achieved from common cyclic carboxylic acids (cyclobutane carboxylate, cyclopentane carboxylate, l-proline, etc.). The whole sequence included only two chemical steps—synthesis of azetidinones, and reduction into azetidines. The obtained spirocyclic amino acids were incorporated into a structure of the known anesthetic drug Bupivacaine. The obtained analogues were more active and less toxic than the original drug. We believe that this discovery will lead to a wide use of spirocyclic building blocks in drug discovery in the near future.
- Kirichok, Alexander A.,Shton, Irina O.,Pishel, Irina M.,Zozulya, Sergey A.,Borysko, Petro O.,Kubyshkin, Vladimir,Zaporozhets, Olha A.,Tolmachev, Andrei A.,Mykhailiuk, Pavel K.
-
supporting information
p. 5444 - 5449
(2018/04/23)
-
- Silver-Catalyzed Three-Component 1,1-Aminoacylation of Homopropargylamines: α-Additions for Both Terminal Alkynes and Isocyanides
-
The reaction of secondary homopropargylamines, isocyanides, and water in the presence of a catalytic amount of silver acetate and subsequent purification by chromatography on silica gel afforded substituted proline amides in good to excellent yields. Primary homopropargylamines underwent a cyclizative Ugi–Joullié three-component reaction with isocyanides and carboxylic acids to afford functionalized N-acyl proline amides. High diastereoselectivity was observed in the synthesis of 4-alkoxy and 4,5-disubstituted proline derivatives. This work represents the first examples of a three-component cyclizative 1,1-aminoacylation of terminal alkynes.
- Tong, Shuo,Piemontesi, Cyril,Wang, Qian,Wang, Mei-Xiang,Zhu, Jieping
-
supporting information
p. 7958 - 7962
(2017/06/27)
-
- 1-Substituted 2-Azaspiro[3.3]heptanes: Overlooked Motifs for Drug Discovery
-
The 2-substituted piperidine core is found in drugs (18 FDA-approved drugs), however, their spirocyclic analogues remain unknown. Described here is the synthesis of spirocyclic analogues for 2-substituted piperidines and a demonstration of their validation in drug discovery.
- Kirichok, Alexander A.,Shton, Iryna,Kliachyna, Maria,Pishel, Iryna,Mykhailiuk, Pavel K.
-
supporting information
p. 8865 - 8869
(2017/07/17)
-
- Access to nitriles from aldehydes mediated by an oxoammonium salt
-
A scalable, high yielding, rapid route to access an array of nitriles from aldehydes mediated by an oxoammonium salt (4-acetylamino-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate) and hexamethyldisilazane (HMDS) as an ammonia surrogate has been developed. The reaction likely involves two distinct chemical transformations: reversible silyl-imine formation between HMDS and an aldehyde, followed by oxidation mediated by the oxoammonium salt and desilylation to furnish a nitrile. The spent oxidant can be easily recovered and used to regenerate the oxoammonium salt oxidant.
- Kelly, Christopher B.,Lambert, Kyle M.,Mercadante, Michael A.,Ovian, John M.,Bailey, William F.,Leadbeater, Nicholas E.
-
supporting information
p. 4241 - 4245
(2015/04/14)
-
- A new reactivity mode for the diazo group: Diastereoselective 1,3-aminoalkylation reaction of β-amino-α-diazoesters to give triazolines
-
A novel mode of reactivity for the diazo group, the 1,3-addition of a nucleophile and an electrophile to the diazo group, has been realized in the intramolecular aminoalkylation of β-amino-α-diazoesters to form tetrasubstituted 1,2,3-triazolines. The reaction exhibited a broad scope, good functional group tolerance, and excellent diastereoselectivity. In addition, a new Au-catalyzed intramolecular transannulation reaction of the obtained propargyl triazolines to give pyrroles has been discovered.
- Kuznetsov, Alexey,Gulevich, Anton V.,Wink, Donald J.,Gevorgyan, Vladimir
-
supporting information
p. 9021 - 9025
(2014/09/29)
-
- Stereochemical lability of azatitanacyclopropanes: Dynamic kinetic resolution in reductive cross-coupling reactions with allylic alcohols
-
Azatitanacyclopropanes (titanaziridines) are shown to be stereochemically labile under reaction conditions for reductive cross-coupling. This fundamental property has been employed to realize highly selective asymmetric coupling reactions with allylic alcohols that proceed by dynamic kinetic resolution. The Royal Society of Chemistry 2013.
- Yang, Dexi,Micalizio, Glenn C.
-
supporting information
p. 8857 - 8859
(2013/09/24)
-
- Three-component coupling sequence for the regiospecific synthesis of substituted pyridines
-
A de novo synthesis of substituted pyridines is described that proceeds through nucleophilic addition of a dithiane anion to an α,β- unsaturated carbonyl followed by metallacycle-mediated union of the resulting allylic alcohol with preformed trimethylsilane-imines (generated in situ by the low-temperature reaction of lithium hexamethyldisilazide with an aldehyde) and Ag(I)- or Hg(II)-mediated ring closure. The process is useful for the convergent assembly of di- through penta-substituted pyridines with complete regiochemical control.
- Chen, Ming Z.,Micalizio, Glenn C.
-
supporting information; experimental part
p. 1352 - 1356
(2012/03/11)
-
- Process optimization of aldol-type reaction by process understanding using in Situ IR
-
A high-yield robust LHMDS-mediated aldol-type reaction of benzyl maltol (2) and benzaldehyde (3) was developed using in situ IR to overcome the problems of low yield and yield fluctuation of the pilot synthesis. In situ IR studies indicated that unexpecte
- Fukui, Yuki,Oda, Shinichi,Suzuki, Hiroyuki,Hakogi, Toshikazu,Yamada, Daisuke,Takagi, Yohei,Aoyama, Yasunori,Kitamura, Hideyuki,Ogawa, Masayoshi,Kikuchi, Junko
-
supporting information
p. 1783 - 1786
(2013/01/15)
-
- Catalytic intermolecular hetero-dehydro-diels-alder cycloadditions: Regioand diasteroselective synthesis of 5,6-dihydropyridin-2-ones
-
A novel catalyzed intermolecular heterodehydro-Diels-Alder reaction between push-pull 1,3-dien-5-ynes and aldimines or silylaldimines is reported. The sequence is promoted both by gold(I) or silver(I) catalysts and leads to the diastereo- and regioselective formation of 5,6- dihydropyridin-2-ones.
- Fernandez-Garcia, Jesus Manuel,Fernandez-Rodriguez, Manuel A.,Aguilar, Enrique
-
supporting information; experimental part
p. 5172 - 5175
(2011/12/04)
-
- Design, Synthesis, and Evaluation of 5′-Diphenyl Nucleoside Analogues as Inhibitors of the Plasmodium falciparum dUTPase
-
Deoxyuridine 5′-triphosphate nucleotidohydrolase (dUTPase) is a potential drug target for malaria. We previously reported some 5′-tritylated deoxyuridine analogues (both cyclic and acyclic) as selective inhibitors of the Plasmodium falciparum dUTPase. Mod
- Hampton, Shahienaz E.,Baragana, Beatriz,Schipani, Alessandro,Bosch-Navarrete, Cristina,Musso-Buendia, J. Alexander,Recio, Eliseo,Kaiser, Marcel,Whittingham, Jean L.,Roberts, Shirley M.,Shevtsov, Mikhail,Brannigan, James A.,Kahnberg, Pia,Brun, Reto,Wilson, Keith S.,Gonzalez-Pacanowska, Dolores,Johansson, Nils Gunnar,Gilbert, Ian H.
-
experimental part
p. 1816 - 1831
(2012/07/03)
-
- New approaches to branched β-amino α-hydroxy acids, taxol side-chain analogs
-
The phenylisothreonine derivatives, taxol side-chain analogs, were synthesized by two routes, one based on the highly stereoselective addition of a phenyl Grignard reagent to the L-threose-derived nitrone 7, and the other using asymmetric α-alkoxyallylation of the ketimine 20 with chiral allyl boron reagents.
- Li, Feng,Li, Zhao-Ming,Yang, Hua,Jaeger, Volker
-
experimental part
p. 431 - 446
(2009/01/31)
-
- Solid-state photolysis of α-azidoacetophenones
-
(Chemical Equation Presented) Solid-state photolysis of 1 yields 2 in a crystal-to-crystal reaction. The reaction takes place by α-cleavage to form a benzoyl and an azido alkyl radical pair. The azido alkyl radicals rearrange into iminyl radicals and N2. The iminyl and benzoyl radicals are held in close proximity within the crystal lattice, which allows them to combine and form 2. X-ray structure analysis, molecular modeling and trapping studies support this mechanism.
- Mandel, Sarah M.,Singh, Pradeep N. D.,Muthukrishnan, Sivaramakrishnan,Chang, Mingxin,Krause, Jeanette A.,Gudmundsdottir, Anna D.
-
p. 4207 - 4210
(2007/10/03)
-
- Asymmetric synthesis of propargylamides via 3,3′-disubstituted binaphthol-modified alkynylboronates
-
(Chemical Equation Presented) Alkynylboronates derived from 3,3′-disubstituted-2,2′-binaphthols react with various N-acylimines to give the expected chiral propargylamides with up to 99% ee. This new methodology was applied to the first enantioselective s
- Wu, T. Robert,Chong, J. Michael
-
-
- Beta-lactam synthesis
-
The present invention is directed to a process for the preparation of β-lactams. Generally, an imine is cyclocondensed with a ketene acetal or enolate to form the β-lactam product in a "one pot" synthesis, this process is generally performed at a higher temperature than conventional processes.
- -
-
Page/Page column 13
(2008/06/13)
-
- Novel dithia-aza-norbornanes as 'stiff' bicyclic dithiazines
-
Addition of lithiated 4,5-dihydro-1,3,5-dithiazines to in situ generated N-silylimines in THF produces 2-(α-aminoalkyl)dithiazines, which rearrange into 3,5-dithia-1-azabicyclo[2.2.1]heptanes upon aqueous workup. These novel bicyclic dithiazines can in tu
- Kurchan, Alexei N.,Wade, Edmir,Kutateladze, Andrei G.
-
p. 1731 - 1733
(2007/10/03)
-
- Iminopinacol coupling with lithium: Electron-transfer mediators
-
The addition of tert-butyl borate or ethyl formate to N-alkylbenzalimines directs the reaction pathway from the Birch reduction to the pinacol-type coupling with lithium in THF; an analogous reaction with a dimethylimmonium salt requires a trace titanium catalyst as the electron-transfer mediator.
- Mistryukov, Electron A.
-
p. 230 - 231
(2007/10/03)
-
- Synthesis of perhydroxazin-4-ones. Competitive Mukaiyama versus hetero Diels-Alder reaction in the cycloaddition of 2-aza-3-trimethylsilyloxy-1,3-butadiene and aldehydes
-
The reactions of 2-aza-3-trimethylsilyloxy-1,3-butadiene with carbonyl dienophiles are described. 2-Aza-1,3-butadienes participate as dienes in the [4+2] cycloaddition with aldehydes to afford perhydroxazin-4-ones in good yields. Experimental results, however, show that a Mukaiyama type two-step reaction must be taken into account. The cycloadducts obtained have proved to be useful intermediates in the synthesis of α-amino-β-hydroxy acids.
- Bongini, Alessandro,Panunzio, Mauro,Bandini, Elisa,Campana, Eileen,Martelli, Giorgio,Spunta, Giuseppe
-
p. 439 - 454
(2007/10/03)
-
- 3,4-dihydro-1-isoquinolinamines: A novel class of nitric oxide synthase inhibitors with a range of isoform selectivity and potency
-
3-Phenyl-3,4-dihydro-1-isoquinolinamine is a weak inhibitor of iNOS and nNOS. Structural variation of 5a results in inhibitors with a range of potency and selectivity for the NOS enzymes, including a potent and very selective iNOS inhibitor 5j.
- Beaton, Haydn,Hamley, Peter,Nicholls, David J,Tinker, Alan C,Wallace, Alan V
-
p. 1023 - 1026
(2007/10/03)
-
- Synthesis of substituted tetrahydroisoquinolines and benzo[d]azepines from phthalan or isochroman and N-silylaldimines
-
The 4,4'-di-tert-butylbiphenyl-catalyzed lithiation of phthalan (1a) and isochroman (1b) in THF at 0°C affords the corresponding functionalized benzyllithiums 2, which by reaction with N-silylaldimines yield, after acid-base work-up, the expected amino al
- Foubelo,Gomez,Gutierrez,Yus
-
p. 1061 - 1064
(2007/10/03)
-
- A trans-stereoselective synthesis of 3-halo-4-alkyl(aryl)-NH-azetidin-2-ones
-
Conrotatory ring closure of 1-halo-3-aza-4-alkyl-1,3-dienes in refluxing toluene gives rise to 3-halo-4-aryl-2-azetidinones in satisfactory yields. Dehalogenation of the resulting β-lactams by tris(trimethylsilyl)silane furnished 3-unsubstituted azetidino
- Bandini, Elisa,Favi, Gianfranco,Martelli, Giorgio,Panunzio, Mauro,Piersanti, Giovanni
-
p. 1077 - 1079
(2007/10/03)
-
- A one-pot aza-Wittig based solution and polymer supported route to amines
-
This paper presents a high yielding one-pot solution phase and polymer supported synthesis of a range of primary and secondary amines starting from azides and aldehydes. The synthesis utilises a tandem process which begins with an aza-Wittig reaction between the aldehyde and an iminophosphorane, followed by reduction, or organometallic 1,2-addition reaction, of the resultant imine. The requisite iminophosphoranes were accessed using the highly efficient Staudinger reaction between the azide starting material and a phosphine. The process was applicable to the solid phase by the use of polymer supported iminophosphoranes and polymer supported cyanoborohydride.
- Hemming,Bevan,Loukou,Patel,Renaudeau
-
p. 1565 - 1568
(2007/10/03)
-
- Lithium perchlorate mediated three component reaction for the preparation of primary amines
-
In the presence of lithium perchlorate in diethyl ether, LPDE, a three- component reaction between aldehydes, sodium hexamethyldisilazane or lithium hexamethyldisilazane, LHMDS, and different nucleophiles proceeds smoothly to afford primary amines in good yields.
- Saidi, Mohammad R.,Javanshir, Shahrzad,Mojtahedi, Mohammad M.
-
p. 330 - 331
(2007/10/03)
-
- Convenient Access to Primary Amines by Employing the Barbier-Type Reaction of N-(Trimethylsilyl)imines Derived from Aromatic and Aliphatic Aldehydes
-
A new versatile preparation of primary amines via benzylation of aromatic and aliphatic aldimines is described. Sonochemical and traditional methods for generation of the reactive intermediates are compared and contrasted. Competitive reactions were analyzed via free energy relationships to support the proposed alkylative mechanism.
- Gyenes, Ferenc,Bergmann, Kathryn E.,Welch, John T.
-
p. 2824 - 2828
(2007/10/03)
-
- Process for the stereoselective preparation of a β-phenylisoserine derivative and its use for the preparation of taxane derivatives
-
This invention relates to a method of stereoselective preparation of a derivative of β-phenylisoserine of formula (I) by the action of an N-carbonyl-benzylimine of formula (II) on an optically active amide of a protected hydroxyacetic acid of formula (III
- -
-
-
- Anti-tumor compounds, pharmaceutical compositions, methods for preparation thereof and for treatment
-
The present invention is directed to novel taxanes useful as chemotherapeutic agents or their precursors. Processes for preparing the novel taxanes include coupling reactions, in the presence of a base, of baccatin of formula (III) or (IV) STR1 with β-lac
- -
-
-
- Reactions of lithium hydridosilylamides with carbonyl compounds and mixtures of carbonyl compounds and chlorotrimethylsilane
-
The lithium hydridosilylamides Me2(H)SiN(Li)R (1: R = CMe3, 2: R = SiMe3) were allowed to react either with the non-enolizable carbonyl compounds CH2=C(Me)CHO, PhCHO and Ph2CO followed by trapping with chlorotrimethylsilane (A), or with mixtures of these carbonyl compounds and chlorotrimethylsilane (B). In the second case the course of the reactions is determined by the carbonyl compound. The composition of the reaction mixtures is nearly the same according to A and B. Main products in the reactions with the aldehydes are the corresponding imines R1CH=NR R1 = CH2=C(Me), Ph) 3, 4, 8, 9 formed by addition of the hydridosilylamides to the C=O group of the aldehydes and subsequent LiOSiMe2H elimination. Partial hydrosilylation of the aldehydes by the hydridosilanolate followed by the trimethylsilylation yields the alkoxydisiloxanes R1CH2OSiMe2OSiMe3 6, 11. In some cases 2 partially reacts under hydrosilylation to give the alkoxydisilazanes R1CH2OSiMe2NHSiMe3 7, 12. The hydrosilylation is the preferred reaction of 1 and 2 with benzophenone. The compounds Ph2CHOSiMe2NHR 13, 14 are obtained. This difference in the reaction behaviour of 1 and 2 towards the aldehydes and benzophenone is mainly due to steric reasons. Depending on the conditions the imines Ph2C=NR 20, 21 may be formed. Ph2CHOSiMe2OSiMe3 (22) is a secondary product of imine formation. In all reactions of 1 and 2 with the carbonyl compounds the corresponding alkoxysilanes R1CH2OSiMe3 (5: R1 = CH2=C(Me), 6: R1 = Ph) and Ph2CHOSiMe3 (15) are generated. Compounds resulting from a reaction of 1 and 2 with chlorotrimethylsilane are produced to minor extent, but only if the molar ratio of amide to carbonyl compounds is not greater than one. The formation of a silanimine intermediate in reaction according to B is not observed.
- Schneider, Jan,Popowski, Eckhard,Fuhrmann, Hans
-
p. 663 - 672
(2007/10/03)
-
- Anti-tumor compounds, pharmaceutical compositions, methods for preparation thereof and for treatment
-
The present invention is directed to novel taxanes useful as chemotherapeutic agents or their precursors. Processes for preparing the novel taxanes include coupling reactions, in the presence of a base, of baccatin of formula (III) or (IV) STR1 with β-lac
- -
-
-
- New and efficient approaches to the semisynthesis of taxol and its C-13 side chain analogs by means of β-lactam synthon method
-
Highly efficient chiral ester enolate-imine condensation giving 3-hydroxy-4-aryl-β-lactams with excellent enantiomeric purity is successfully applied to the asymmetric synthesis of the enantiomerically pure taxol C-13 side chain, N-benzoyl-(2R,3S)-3-phenyl-isoserine and its analogs. (3R,4S)-N-benzoyl-3-(1-ethoxyethoxy)-4-phenyl-2-azetidinone readily derived from the 3-hydroxy-4-phenyl-β-lactam is coupled with protected baccatin IIIs, followed by deprotection to give optically pure taxol and 10-deacetyl-7,10-bis(Troc)-taxol in good yields. Fully assigned 1H, 13C, and 2D (COSY and HETCOR) NMR spectra of taxol thus synthesized are shown and discussed.
- Ojima, Iwao,Habus, Ivan,Zhao, Mangzhu,Zucco, Martine,Park, Young Hoon,Sun, Chung Ming,Brigaud, Thierry
-
p. 6985 - 7012
(2007/10/02)
-
- N-Amination Using N-Methoxycarbonyl-3-phenyloxaziridine. Direct Access to Chiral Nβ-Protected α-Hydrazinoacids and Carbazates
-
Primary and secondary amines =NH, including α-aminoacids, can be converted under mild conditions to the corresponding carbazates =N-NH-CO2Me, on reaction with N-methoxycarbonyl-3-phenyloxaziridine 1.
- Vidal, Joelle,Drouin, Jacques,Collet, Andre
-
p. 435 - 437
(2007/10/02)
-
- A REGIO- AND STEREOSELECTIVE SYNTHESIS OF SUBSTITUTED PIPERIDONES
-
The new activated 2-aza-1,3-dienes 1 are readily prepared by acylation of N-trimethylsilylimines 3.They react with electrophilic olefins to yield substituted piperidones 4 and 6 with high diastereoselectivity.
- Bayard, Philippe,Ghosez, Leon
-
p. 6115 - 6118
(2007/10/02)
-
- A SYNTHETIC APPROACH TO AZETIDINONES FROM NITRILES AND LITHIUMTRIETHOXYALUMINIUM HYDRIDE.
-
A convenient one-pot process for direct conversion of nitriles to 3,4-disubstituted azetidinones has been developed.
- Andreoli, P.,Cainelli, G.,Contento, M.,Giacomini, D.,Martelli, G.,Panunzio, M.
-
p. 1695 - 1698
(2007/10/02)
-
- Reaction of Silyl Ketene Acetals with N-Trimethylsilyl Imines: a Route to N-Unsubstituted Azetidin-2-ones
-
Reaction of N-trimethylsilyl imines with silyl ketene acetals in the presence of ZnI2 and t-butyl alcohol, followed by treatment in situ of the intermediate N-silyl β-aminoesters with MeMgBr, leads to N-unsubstituted azetidin-2-ones in good yield.
- Colvin, Ernest W.,McGarry, Daniel G.
-
p. 539 - 540
(2007/10/02)
-
- N-Trimethylsilyl Imines: Applications to the Synthesis of β-Lactams
-
Ester enolates and N-trimethylsilyl imines react to afford N-protio-β-lactams.The stereochemical course of the reaction depends on the ester enolate geometry.Therefore (E)-enolates give mainly cis β-lactams while (Z)-enolates give nearly equal mixtures of cis and trans β-lactams.The use of ethyl β-hydroxybutyrate as the ester component allows the preparation of β-lactams of potential use in carbapenem synthesis.The differences in the behavior of N-trimethylsilyl and N-aryl imines in ester-imine condensations are also discussed.
- Ha, Deok-Chan,Hart, David J.,Yang, Teng-Kuei
-
p. 4819 - 4825
(2007/10/02)
-
- Preparation of Primary Amines and 2-Azetidinones via N-Trimethylsilyl Imines
-
Nonenolizable aldehydes react with lithium bis(trimethylsilyl)amide at ambient temperatures to afford solutions of N-trimethylsilyl aldimines.Treatment of these solutions with Grignard reagents or alkyllithiums followed by an aqueous workup gives primary amines in moderate to excellent yields.Treatment of N-trimethylsilyl aldimines with ester enolates provides an expedient route to 1-unsubstituted 2-azetidinones.
- Hart, David J.,Kanai, Ken-ichi,Thomas, Dudley G.,Yang, Teng-Kuei
-
p. 289 - 294
(2007/10/02)
-