- Intramolecular Cyclization of 3,3-Diarylpropenylamides of Electron-Deficient Alkenes: Stereoselective Synthesis of Functionalized Hexahydrobenzo[f]isoindoles
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Intramolecular Diels–Alder reactions of various 3,3-diarylpropenylamides of electron-deficient alkenes to give hexahydrobenzo[f]isoindoles were investigated. Reaction of 1,1,2-ethenetricarboxylic acid 1,1-diethyl ester with 3,3-diaryl-2-propen-1-amines under the amide formation conditions gave the tricyclic compounds in sequential processes involving intramolecular Diels–Alder reaction. The reaction gave cis- and trans-fused tricyclic compounds selectively, depending on the substituents on the benzene ring, reaction temperature and solvent. In the reaction with dissymmetrically substituted 3,3-diaryl-2-propen-1-amines, trans-substituted aryl group reacted mainly as a styrene component. Amides of electron-deficient alkenic carboxylic acids such as fumarate do not undergo cyclization at room temperature sequentially and the reaction on heating gave trans-fused hexahydrobenzo[f]isoindoles. The origin of the observed stereoselectivity has been examined by the DFT calculations.
- Sugiura, Hirotaka,Yamazaki, Shoko,Go, Kakeru,Ogawa, Akiya
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- Stereoselective synthesis of cis-2,6-disubstituted piperidines from 1,2-cyclic sulfamidates
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Diastereoselective synthesis of cis-2,6-disubstituted piperidines from 1,2-cyclic sulfamidates is described. Regioselective ring-opening reactions of 1,2-cyclic sulfamidates derived from L-phenylalanine, alanine, valine, norvaline with the ketal protected acetylide with a phenyl substituent proceed smoothly to form the N-sulfamate intermediates which on acidic hydrolysis give alkynylated amines with the ketal group intact. Hydrogenation of the alkynylated amines, debenzylation, ketal deprotection, subsequent cyclization (of aminoketones) and stereoselective hydrogenation of the cyclic iminium ion intermediates afford the corresponding cis-2,6-disubstituted piperidines in high diastereoselectivity (98% ≥ d.e.) with good chemical yields (68–86%). The present approach provides a novel route for the stereoselective synthesis of cis-2,6-disubstituted piperidines.
- Eskici, Mustafa,Karanfil, Abdullah
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- Lanthanide-Catalyzed Tandem Addition of Amines to Cyanoalkenes: Synthesis of Cyclic Amidines
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A tandem insertion of aliphatic nitriles and unactivated alkenes to the N-H bond of secondary aliphatic amines catalyzed by simple trialkyl rare-earth metal complexes was disclosed. This reaction provides a highly atom-economic and stereoselective way to a range of cyclic amidines under mild reaction conditions.
- Chai, Zhuo,Hou, Jinsong,Yang, Gaosheng
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supporting information
(2022/01/04)
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- Visible Light-Mediated Synthesis of Enantiopure γ-Cyclobutane Amino and 3-(Aminomethyl)-5-phenylpentanoic Acids
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A visible light-mediated [2+2] photocycloaddition of amide-linked dienes using [Ir(dtb-bpy)(dF(CF3)ppy)2]PF6 as triplet sensitizer was applied to generate a variety of N-tert-butyl, N-benzyl- and N-tert-butoxycarbonyl-protected 3-azabicyclo[3.2.0]heptan-2-ones in good yields and with good diastereoselectivity. Density functional theory calculations shed light on the conformational prerequisites for the [2+2] photocycloaddition. The bicyclic key structures could be readily transformed into γ-cyclobutane amino acids. For the obtained racemic 3-phenyl-2-aminocyclobutane-1-carboxylic acid the resolution with chiral oxazolidin-2-one is demonstrated to allow access to both enantiomers. Alternatively, a chiral auxiliary approach led as well to the enantiomerically pure target compound. Finally, the synthesis of either enantiomer of 3-(aminomethyl)-5-phenylpentanoic acid, the racemate being described as an anticonvulsant, is described.
- Kerres, Sabine,Plut, Eva,Malcherek, Simon,Rehbein, Julia,Reiser, Oliver
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supporting information
(2019/02/07)
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- Visible Light-Mediated Synthesis of Enantiopure g-Cyclobutane Amino and 3-(Aminomethyl)-5-phenylpentanoic Acids
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A visible light-mediated [2+2] photocycloaddition of amide-linked dienes using [Ir(dtb-bpy)(dF(CF3)ppy)2]PF6 as triplet sensitizer was applied to generate a variety of N-tert-butyl, N-benzyl- and N-tert-butoxycarbonyl-protected 3-aza-bicyclo[3.2.0]heptan-2-ones in good yields and with good diastereoselectivity. Density functional theory calculations shed light on the conformational prerequisites for the [2+2] photocycloaddition. The bicyclic key structures could be readily transformed into g-cyclobutane amino acids. For the obtained racemic 3-phenyl-2-aminocyclobu-tane-1-carboxylic acid the resolution with chiral oxazolidin-2-one is demonstrated to allow access to both enantiomers. Alternatively, a chiral auxiliary approach led as well to the enantiomerically pure target compound. Finally, the synthesis of either enantiomer of 3-(aminomethyl)-5-phenylpentanoic acid, the racemate being described as an anticonvulsant is described.
- Kerres, Sabine,Plut, Eva,Malcherek, Simon,Rehbein, Julia,Reiser, Oliver
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supporting information
p. 1400 - 1407
(2019/10/28)
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- Unexpected Rearrangement of N-Allyl-2-phenyl-4,5-Dihydrooxazole-4-Carboxamides to Construct Aza-Quaternary Carbon Centers
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The unexpected rearrangement of N-allyl-2-phenyl-4,5-dihydrooxazole-4-carboxamides in the presence of LiHMDS has been found. The key features are: (1) the net reaction consisted of 1,3-migration of the N-allyl group, (2) the rearrangement produced a congested aza-quaternary carbon center, (3) both cyclic and acyclic substrates underwent the unexpected rearrangement to afford products in moderate to high yields, and (4) the reaction seemed to be highly stereoselective. In addition, a plausible mechanism has been discussed.
- Choi, Goyeong,Jo, Seoyoung,Mun, Juyeon,Jeong, Yonguk,Kim, Seok-Ho,Jung, Jong-Wha
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- Expanding the Boundaries of Water-Tolerant Frustrated Lewis Pair Hydrogenation: Enhanced Back Strain in the Lewis Acid Enables the Reductive Amination of Carbonyls
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The development of a boron/nitrogen-centered frustrated Lewis pair (FLP) with remarkably high water tolerance is presented. As systematic steric tuning of the boron-based Lewis acid (LA) component revealed, the enhanced back-strain makes water binding increasingly reversible in the presence of relatively strong base. This advance allows the limits of FLP's hydrogenation to be expanded, as demonstrated by the FLP reductive amination of carbonyls. This metal-free catalytic variant displays a notably broad chemoselectivity and generality.
- Dorkó, éva,Szabó, Márk,Kótai, Bianka,Pápai, Imre,Domján, Attila,Soós, Tibor
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supporting information
p. 9512 - 9516
(2017/08/01)
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- Synthesis of Cyclic Guanidines Bearing N-Arylsulfonyl and N-Cyano Protecting Groups via Pd-Catalyzed Alkene Carboamination Reactions
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Palladium-catalyzed carboamination reactions of N-allylguanidines bearing cleavable N-cyano or N-arylsulfonyl protecting groups are described. The reactions afford cyclic guanidine products in good yield, and transformations of substrates bearing internal alkenes proceed with high diastereoselectivity. Deuterium labeling studies indicate these transformations proceed via anti-aminopalladation pathways.
- Peterson, Luke J.,Luo, Jingyi,Wolfe, John P.
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supporting information
p. 2817 - 2820
(2017/06/07)
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- Simple Metal-Free Direct Reductive Amination Using Hydrosilatrane to Form Secondary and Tertiary Amines
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This work describes the use of cheap, safe, and easy-to-handle hydrosilatrane as the reductant in direct reductive amination reactions. This efficient method enables a facile, metal-free access to secondary and tertiary amines from a wide range of aldehydes and ketones, with the synthesis of tertiary amines requiring no additives at all. This reaction demonstrates excellent functional group tolerance, chemoselectivity, and scalability. (Figure presented.).
- Varjosaari, Sami E.,Skrypai, Vladislav,Suating, Paolo,Hurley, Joseph J. M.,Lio, Ashley M. De,Gilbert, Thomas M.,Adler, Marc J.
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supporting information
p. 1872 - 1878
(2017/06/09)
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- Direct use of allylic alcohols and allylic amines in palladium-catalyzed allylic amination
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Allylic alcohols and allylic amines were directly utilized in a Pd-catalyzed hydrogen-bond-activated allylic amination under mild reaction conditions in the absence of any additives. The cooperative action of a Pd-catalyst and a hydrogen-bonding solvent is most likely responsible for its high reactivity. The catalytic system is compatible with a variety of functional groups and can be used to prepare a wide range of linear allylic amines in good to excellent yields. Furthermore, this methodology can be easily applied to the one-step synthesis of two drugs, cinnarizine and naftifine, on a gram scale.
- Jing, Jiangyan,Huo, Xiaohong,Shen, Jiefeng,Fu, Jingke,Meng, Qinghua,Zhang, Wanbin
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supporting information
p. 5151 - 5154
(2017/07/12)
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- Intramolecular [2 + 2] and [4 + 2] Cycloaddition Reactions of Cinnamylamides of Ethenetricarboxylate in Sequential Processes
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Intramolecular [2 + 2] and [4 + 2] cycloaddition reactions of cinnamylamides of ethenetricarboxylate in sequential processes have been studied. Reaction of 1,1-diethyl 2-hydrogen ethenetricarboxylate and trans-cinnamylamines in the presence of EDCI/HOBt/Et3N led to pyrrolidine products in one pot, via intramolecular [2 + 2], [4 + 2], and some other cyclizations. The types of the products depend on the substituents on the benzene ring and the reaction conditions. Reaction of cinnamylamines without substituents on the benzene ring and with halogens and OMe on the para position at room temperature gave cyclobutane-fused pyrrolidines as major products via [2 + 2] cycloaddition. The reaction at 80 °C in 1,2-dichloroethane gave δ-lactone fused pyrrolidines as major products, probably via ring-opening of the cyclobutanes. Interestingly, reaction of 1,1-diethyl 2-hydrogen ethenetricarboxylate and cinnamylamines bearing electron-withdrawing groups such as NO2, CN, CO2Me, CO2Et, and CF3 on ortho and para positions in the presence of EDCI/HOBt/Et3N at room temperature or at 60-80 °C gave tetrahydrobenz[f]isoindolines via [4 + 2] cycloaddition as major products. DFT studies have been performed to explained the observed [2 + 2]/[4 + 2] selectivity.
- Yamazaki, Shoko,Sugiura, Hirotaka,Ohashi, Shinnosuke,Ishizuka, Keisuke,Saimu, Rina,Mikata, Yuji,Ogawa, Akiya
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p. 10863 - 10886
(2016/11/29)
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- Anti-Markovnikov rearrangement in sulfur mediated allylic C-H amination of olefins
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Cationic rearrangement reactions usually follow Markovnikov's rule to give more substituted carbocations as stable intermediates. During our study on sulfur mediated allylic C-H amination of olefins, very rare cases of anti-Markovnikov rearrangement from secondary carbocations toward primary carbocations or primary triflates were observed.
- Zhang, Zhong,Du, Hongguang,Xu, Jiaxi,Li, Pingfan
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supporting information
p. 11547 - 11550
(2016/10/03)
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- Iron-Catalyzed Allylic Amination Directly from Allylic Alcohols
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Allylic amination, directly from alcohols, has been demonstrated without any Lewis acid activators using an efficient and regiospecific molecular iron catalyst. Various amines and alcohols were employed and the reaction proceeded through the oxidation/reduction (redox) pathway. A direct one-step synthesis of common drugs, such as cinnarizine and nafetifine, was exhibited from cinnamyl alcohol that produced water as side product. The iron way! A direct amination of allylic alcohols has been demonstrated without the need of Lewis acid activators using an efficient and regiospecific molecular iron catalyst. A range of amines and alcohols were tolerated, and the reaction was found to procced through an oxidation/reduction (redox) pathway (see scheme).
- Emayavaramban, Balakumar,Roy, Moumita,Sundararaju, Basker
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supporting information
p. 3952 - 3955
(2016/03/16)
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- Ruthenium-catalyzed regioselective allylic trifluoromethylthiolation reaction
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An efficient Ru-catalyzed regioselective allylic trifluoromethylthiolation reaction of allylic carbonates was developed. The linear allylic trifluoromethyl thioethers were obtained in 52-91% yields. Mechanistic investigation revealed that this reaction proceeds via a double allylic trifluoromethylthiolation sequence.
- Ye, Ke-Yin,Zhang, Xiao,Dai, Li-Xin,You, Shu-Li
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p. 12106 - 12110
(2015/01/09)
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- A cyclization-rearrangement cascade for the synthesis of structurally complex chiral gold(I)-aminocarbene complexes
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A facile synthesis of chiral cyclic alkyl aminocarbene-gold(I) complexes from gold-free 1,7-enyne substrates was developed. The novel cyclization-rearrangement reaction sequence is triggered by the addition of (Me2S)AuCl to different 1,7-enynes and leads to structurally unique carbene-gold(I) complexes in high yields. These novel complexes are catalytically active and inhibit the proliferation of different human cancer cell lines.
- Kolundzic, Filip,Murali, Annamalai,Perez-Galan, Patricia,Bauer, Jonathan O.,Strohmann, Carsten,Kumar, Kamal,Waldmann, Herbert
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supporting information
p. 8122 - 8126
(2014/08/18)
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- Deammoniative condensation of primary allylic amines with nonallylic amines
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An unprecedented deammoniative condensation reaction of primary allylic amines with nonallylic amines has been developed through C-N bond cleavage. In the presence of 5 mol% palladium diacetate, 10 mol% 1,4-bis(diphenylphosphino) butane (dppb), and 5 mol% p-toluenesulfonic acid (TsOH), a range of α-unbranched primary allylic amines smoothly underwent deammoniative condensation with nonallylic amines in an α-selective fashion to give structurally diverse secondary and tertiary amines in good to excellent yields and E selectivity. Replacing dppb with racemic 2,2-bis(diphenylphosphino)-1,1- binaphthyl (BINAP) permitted the deammoniative condensation of enantioenriched α-chiral primary allylic amines with nonallylic amines to proceed with complete retention of configuration. Electrospray ionization (ESI) mass spectrometric analysis of the reaction mixture permitted the identification of some π-allylpalladium intermediates, and plausible mechanisms have been proposed to account for the regioselectivity and stereospecificity of the deammoniative condensation reaction. A range of enantioenriched primary allylic amines underwent palladium/acid-catalyzed direct substitution with nonallylic amines in a stereospecific manner. Copyright
- Wang, Yong,Li, Manbo,Ma, Xiantao,Liu, Congrong,Gu, Yonghong,Tian, Shi-Kai
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p. 741 - 751
(2014/10/15)
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- N-heterocyclic carbene C,S palladium(II) π-allyl complexes: Synthesis, characterization, and catalytic application in allylic amination reactions
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A series of five-membered N-heterocyclic carbene C,S palladium(II) π-allyl complexes were successfully developed and characterized. Structural analyses of these complexes revealed that the organopalladium chelates adopt a skew-envelope conformation with a
- Krishnan, Deepa,Wu, Meiyi,Chiang, Minyi,Li, Yongxin,Leung, Pak-Hing,Pullarkat, Sumod A.
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supporting information
p. 2389 - 2397
(2013/06/27)
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- Tsuji-trost N-allylation with allylic acetates by using a cellulose-palladium catalyst
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Allylic amines were synthesized by a simple procedure using a biodegradable and easily recyclable heterogeneous cellulose-Pd catalyst through N-allylation of primary and secondary amines. The scope of this protocol includes aliphatic and benzylamines with substituted and unsubstituted allyl acetates and culminates in high yield syntheses. The highlights of the protocol include a ligand-free reaction, simple workup, and catalyst recyclability. Allylic amines were synthesized by N-allylation of primary and secondary amines through a simple and easy procedure involving the use of a heterogeneous cellulose-Pd catalyst; aliphatic and benzylamines underwent facile reaction with substituted and unsubstituted allyl acetates in high yields. Copyright
- Vaddula, Buchi Reddy,Saha, Amit,Varma, Rajender S.,Leazer, John
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supporting information
p. 6707 - 6709
(2013/01/15)
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- Enantiomerically Pure P,N Chelates Based on Phospholene Rings: Palladium Complexes and Catalytic Applications in Allylic Substitution
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The synthesis of optically pure 2-pyridylphospholene ligands by diastereomeric resolution of PdII complexes, bearing the corresponding racemic P,N ligand and (R)-α-methylbenzylamine, by means of fractional, crystallisation is described. A full coordination study of palladium complexes containing 2pyridylphospholene and the corresponding phosphole ligands, both in solution (by means of NMR spectroscopy) and in the solid state (by X-ray diffraction), was carried out. These ligands were evaluated, in Pd-catalysed allylic substitution of racemic substrates (rac-3-acetoxy-l,3- diphenyl-l-propene and rac-3-acetoxy-l-cyclohexene) and (E)-3-acet-oxy-1-phenyl- 1-propene. A modelling study of the palladium allylic intermediates was performed, in order to justify the asymmetric induction observed with the 2-pyridylphospholene ligands.
- Leca, Francois,Fernandez, Fernando,Muller, Guillermo,Lescop, Christophe,Reau, Regis,Gomez, Montserrat
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scheme or table
p. 5583 - 5591
(2010/06/15)
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- Allosteric functional switch of neurokinin A-mediated signaling at the neurokinin NK2 receptor: Structural exploration
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The neurokinin NK2 receptor is known to pre-exist in equilibrium between at least three states: restinginactive, calcium-triggering, and cAMP-producing. Its endogeneous ligand, NKA, mainly induces the calcium response. Using a FRET-based assay, we have previously discovered an allosteric modulator of the NK2 receptor that has the unique ability to discriminate among the two signaling pathways: calcium-signaling is not affected while cAMP signaling is significantly decreased. A series of compounds have been prepared and studied in order to better understand the structural determinants of this allosteric functional switch of a GPCR. Most of them display the same allosteric profile, with smooth pharmacomodulation. One compound however exhibits significantly improved modulatory properties of NKA induced signaling when compared to the original modulator. 2009 American Chemical Society.
- Valant, Céline,Maillet, Emeline,Bourguignon, Jean-Jacques,Bucher, Bernard,Utard, Valérie,Galzi, Jean-Luc,Hibert, Marcel
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experimental part
p. 5999 - 6011
(2010/03/24)
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- Reactivity of cyclic sulfamidates towards phosphonate-stabilised enolates: Synthesis and applications of α-phosphono lactams
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Five and six ring α-phosphono lactams 14-20 are available by reaction of 1,2- and 1,3-cyclic sulfamidates respectively with enolates derived from ethyl dialkylphosphonoacetates 3 and 4. Subsequent Wadsworth-Emmons olefination provides the enantiomerically
- Bower, John F.,Williams, Andrew J.,Woodward, Hannah L.,Szeto, Peter,Lawrence, Ron M.,Gallagher, Timothy
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p. 2636 - 2644
(2008/03/11)
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- Cyclic sulfamidates as precursors to alkylidene pyrrolidines and piperidines
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(Chemical Equation Presented) The reaction of the dienolate of ethyl acetoacetate (and related dienolates) with a range of 1,2- and 1,3-cyclic sulfamidates provides an entry to substituted and enantiopure alkylidenated pyrrolidines and piperidines. These
- Bower, John F.,Szeto, Peter,Gallagher, Timothy
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p. 4909 - 4912
(2008/03/13)
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- Enantiopure 1,4-benzoxazines via 1,2-cyclic sulfamidates. Synthesis of levofloxacin
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1,2-Cyclic sulfamidates undergo efficient and regiospecific nucleophilic cleavage with 2-bromophenols (and related anilines and thiophenols), followed by Pd(0)mediated amination to provide an entry to substituted and enantiomerically pure 1,4-benzoxazines (and quinoxalines and 1,4-benzothiazines). This chemistry provides a short and efficient entry to (3S)-3-methyl-1,4-benzoxazine 19, a late stage intermediate in the synthesis of levofloxacin.
- Bower, John F.,Szeto, Peter,Gallagher, Timothy
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p. 3283 - 3286
(2008/02/12)
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- Direct use of allylic alcohols for platinum-catalyzed monoallylation of amines
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A new direct catalytic amination of allylic alcohols promoted by the combination of platinum and a large bite-angle ligand DPEphos was developed in which the allylic alcohol was effectively converted to a π-allylplatinum intermediate without the use of an activating reagent. The use of the DPEphos ligand was essential for obtaining high catalyst activity and high monoallylation selectivity of primary amines, allowing the formation of a variety of monoallylation products in good to excellent yield.
- Utsunomiya, Masaru,Miyamoto, Yoshiki,Lpposhi, Junji,Ohshima, Takashi,Mashima, Kazushi
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p. 3371 - 3374
(2008/02/12)
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- Iridium-catalyzed, asymmetric amination of allylic alcohols activated by lewis acids
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The direct, Ir-catalyzed, regio- and enantioselective amination of allylic alcohols with Lewis acid activators to form branched allylic amine products is reported. The reactions of arylamines, benzylic amines, and secondary aliphatic amines in the presence of Nb(OEt)5 as activator occurred with high regioselectivities and high enantioselectivities. These results led to the development of Ir-catalyzed reactions of allylic alcohol with arylamines and BPh3 as activator in catalytic amounts. These reactions are rare examples of enantioselective substitutions of allylic alcohols. They are particularly unusual examples of the substitution of allylic alcohols to generate branched substitution products from monosubstituted allylic alcohols and of enantioselective substitutions of allylic alcohols with amine nucleophiles. Copyright
- Yamashita, Yasuhiro,Gopalarathnam, Apsara,Hartwig, John F.
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p. 7508 - 7509
(2008/02/11)
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- Reactivity of cyclic sulfamidates towards sulfur-stabilised enolates. Stereocontrolled synthesis of functionalised lactams
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A structurally representative series of 1,2- and 1,3-cyclic sulfamidates react with enolates derived from methyl α-phenylthioacetate 9b to give 5- and 6-substituted α-phenylthio lactams 20-24. These products provide, via the corresponding sulfoxides, an e
- Bower, John F.,Chakthong, Suda,Venda, Jakub,Williams, Andrew J.,Lawrence, Ron M.,Szeto, Peter,Gallagher, Timothy
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p. 1868 - 1877
(2008/02/02)
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- Phosphoramidite ligands in iridium-catalyzed allvlic substitution
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A new phosphoramidite ligand was used in the iridium-catalyzed allylic substitution reaction. This permitted high regio- and enantioselectivities on a wide variety of substrates and nucleophiles. Because of the stereospecificity of the reaction obtained by using branched substrates, a kinetic resolution reaction was attempted. The origin of the impressive efficiency of this ligand in terms of kinetics was explored in detail, as was the role of the substituent in the ortho-position of the amine moiety.
- Polet, Damien,Alexakis, Alexandre,Tissot-Croset, Karine,Corminboeuf, Clemence,Ditrich, Klaus
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p. 3596 - 3609
(2008/02/04)
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- Palladium/BINAP(S)-catalyzed asymmetric allylic amination
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(Chemical Equation Presented) The enantioselective allylic amination of acyclic allylic carbonates catalyzed by a palladium/(S)-BINAP(S) system was investigated. Amination of several substrates proceeded with high ee. Crotyl carbonates show an unusually high regioselectivity for the branched isomer. The use of (S)-TolBINAP(S) and (S)-3,5-xylyl-BINAP(S) as ligands was found to increase the enantioselectivity of the aminations. A P,S binding mode of the BINAP(S) ligand was found in an X-ray crystallographic study.
- Faller,Wilt, Jeremy C.
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p. 633 - 636
(2007/10/03)
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- ENANTIOSELECTIVE PHOSPHORAMIDITE COMPOUNDS AND CATALYSTS
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This invention relates to phosphoramidite compounds and catalyst complexes which can be used to provide enantioselective reactions including hydroamination reactions, etherification reactions and conjugate addition reactions and allylic substitution reactions, among others. In a first aspect, the present invention is directed to phosphoramidite and related compounds according to general structure (I), where Z is absent or is a group containing O, N or S, preferably O; R1 and R2 are independently an optionally substituted C1-12 alkyl group, an optionally substituted (CH2)n-aromatic group or (CH2)n-heteroaromatic group, or are linked together to form an optionally substituted aliphatic or (CH2)n-aromatic dianion of a diol, diamine, dithiol, aminoalcohol, aminohiolate or a alcoholthiol group; R3’ and R3 are each independently H, an optionally substituted C1-C12 alkyl group or an optionally substituted (CH2)n-aromatic group with the proviso that R3’ and R3 are not both H, or together R3’ and R3 form an optionally substituted C5-C15 saturated or unsaturated carbocyclic ring; R4 is H, an optionally substituted C1-C12 alkyl group or an optionally substituted (CH2)n-aromatic group; R5 is absent, H, an optionally substituted C1-C12 alkyl group or an optionally substituted (CH2)n-aromatic or (CH2)n-heteroaromatic group; Ra and Ra’ are each independently H or a C1-C3 alkyl group, or Ra and Ra’ together with the carbon to which they are attached form a optionally substituted C5-C15 saturated or unsaturated carbocyclic or heterocyclic ring, or an aromatic or heteroaromatic ring; R6 and R7 are each independently H, an optionally substituted C1-C12 alkyl group or an optionally substituted (CH2)n-aromatic group, with the proviso that R5, R6 and R7 cannot simultaneously be H, and when Ra and Ra’, together with the carbon to which they are attached, form a carbocyclic ring, heterocyclic ring or an aromatic or heteroaromatic ring, R5 is absent or is preferably H; R6 and R7 are preferably H or CH3; and each n is independently 0, 1, 2, 3, 4, 5 or 6 and wherein at least one of the carbon atoms attached to the nitrogen of the phosphoramidite group is a chiral center.
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Page/Page column 53; 55-57
(2010/02/14)
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- ENANTIOSELECTIVE AMINATION AND ETHERIFICATION___________________
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The present invention is directed to a catalyst composition, comprising: (1) a catalyst precursor having the general structure MSXn wherein M is a transition metal selected from the group consisting of iridium, molybdenum, and tungsten; S is a coordinating ligand; X is a counterion; and n is an integer from 0 to 5; and (2) a phosphoramidite ligand having the structure wherein O-Cn-O is an aliphatic or aromatic diolate and wherein R1, R2, R3 and R4 are selected from the group consisting of substituted or unsubstituted aryl groups, substituted or unsubstituted heteroaryl groups, substituted or unsubstituted aliphatic groups, and combinations thereof, with the proviso that at least one of R1, R2, R3, or R4 must be a substituted or unsubstituted aryl or heteroaryl group. The present invention is also directed to activated catalysts made from the above catalyst composition, as well as methods of allylic amination and etherification using the above catalysts.
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- Lewis Acid Mediated [2,3]-Sigmatropic Rearrangement of Allylic α-Amino Amides
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Boron trifluoride and BBr3 mediated [2,3]-sigmatropic rearrangements of allylic α-amino amides have been developed affording secondary amines in good yields. (E)-Crotyl and (E)-cinnamyl α-amino amides 2b and 2c exhibit excellent syn-diastereoselectivity upon rearrangement with either Lewis acid. The allylic amine 2a forms upon treatment with BF 3 or BBr3 a five-membered heterocylic complex in which a single halide anion has been displaced by the carbonyl oxygen atom. The structures of the Lewis acid-amine complexes were elucidated using NMR spectroscopy. A plausible reaction mechanism, based on DFT calculations, is presented. Thus, BF3- or BBr3-complexed allylic amines 2 are shown to preferentially proceed, after deprotonation, via an endo transition state.
- Blid, Jan,Brandt, Peter,Somfai, Peter
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p. 3043 - 3049
(2007/10/03)
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- A highly effective phosphoramidite ligand for asymmetric allylic substitution
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Very high enantioselectivity has been achieved both in the copper-catalyzed alkylation of allylic substrates by Grignard and organozinc reagents and in the iridium-catalyzed animation of cinnamyl carbonate by employing a very efficient phosphoramidite ligand (see scheme).
- Tissot-Croset, Kanne,Polet, Damien,Alexakis, Alexandre
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p. 2426 - 2428
(2007/10/03)
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- Synthesis of allylamines from alkynes and iminium ions
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The iminium salt Bn2N+=CH2 SnCl 5- undergoes ene reactions with inverse electron demand with alkynes and with the triple bond of enynes to give benzylideneammonium ions in aprotic solvents. Their hydr
- Rehn, Susanne,Ofial, Armin R.,Mayr, Herbert
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p. 1790 - 1796
(2007/10/03)
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- Solid-phase synthesis of 4-methylene pyrrolidines and allylic amines using palladium-activated allylic linkers
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The solid-phase synthesis of 4-methylene pyrrolidines and allylic amines has been achieved using palladium-catalysed nucleophilic cleavage of allylic linkages. Six pyrrolidines were synthesised in five steps from a carboxyethyl resin 20, where the key transformations included a Lewis-acid promoted imino-Sakurai type reaction and reductive alkylation prior to the final palladium-catalysed cyclisation cleavage of the allylic carboxylate linkage. Allylic carboxylate resin 22 was also shown to undergo "traceless" cleavage using various hydride sources in the presence of catalytic palladium. A more robust allylic ether linkage was also investigated. Starting from a phenol resin 36, a number of 3-aryl-allylaniines were prepared using a palladium-catalysed nucleophilic cleavage reaction.
- Brown, Richard C.D.,Fisher, Martyn L.,Brown, Lynda J.
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p. 2699 - 2709
(2007/10/03)
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- Regio- and enantioselective allylic amination of achiral allylic esters catalyzed by an iridium-phosphoramidite complex
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A new catalytic asymmetric process, the iridium-catalyzed enantioselective allylic amination of (E)-cinnamyl and terminal aliphatic allylic carbonates, was developed by exploring complexes of chiral phosphoramidites. The reaction provided branched secondary and tertiary allylic amines in high yields with excellent regio- and enantioselectivity (13 examples over 94% ee). Although the reactions in polar solvent such as DMF, EtOH, and MeOH were fast, they gave low enantiomeric excesses. In contrast, reactions in THF displayed the most suitable balance of rate and enantioselectivity. Both the binaphthol unit and the disubstituted amine in the phosphoramidite affected reactivity and selectivity, and complexes of O,O′-(R)-(1,1′-dinaphthyl-2,2′-diyl)-N,N′-di-(R,R)-1-phenylethylphosphoramidite provided the highest reactivity and selectivity. Primary and cyclic secondary amines reacted at room temperature, and acyclic diethylamine reacted at 50 °C. p-Methoxy-substituted cinnamyl carbonate reacted similarly to the unsubstituted cinnamyl carbonate, but the o-methoxy-substituted substrate gave lower enantiomeric excess. High ee's were also observed for the products from the reaction of furanyl- and alkyl-substituted (E)-allylic carbonates. Copyright
- Ohmura, Toshimichi,Hartwig, John F.
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p. 15164 - 15165
(2007/10/03)
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- Palladium-tetraphosphine catalysed allylic substitution in water
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The cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane/[PdCl (C3H5)]2 system catalyses allylic amination in water with very high substrate/catalyst ratio in good yields. A turnover number of 980 000 can be obtained for the addition of dipropylamine to allyl acetate in the presence of this catalyst.
- Feuerstein, Marie,Laurenti, Dorothée,Doucet, Henri,Santelli, Maurice
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p. 2313 - 2315
(2007/10/03)
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- Iridium complex-catalyzed allylic amination of allylic esters
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Iridium complex-catalyzed allylic amination of allylic carbonates was studied. The solvent strongly affected the catalytic activity. The use of a polar solvent such as EtOH is essential for obtaining the products in high yield. The reaction of (E)-3-substituted-2-propenyl carbonate and 1-substituted-2-propenyl carbonate with pyrrolidine in the presence of a catalytic amount of [Ir(COD)Cl]2 and P(OPh)3 (P/Ir=2) gave a branch amine with up to 99% selectivity. Both secondary and primary amines could be used for this reaction. When a primary amine was used, selective monoallylation occurred. No diallylation product was obtained. The reaction of 1,1-disubstituted-2-propenyl acetate with amines exclusively gave an α,α-disubstituted allylic amine. This reaction provides an alternative route to the addition of an organometallic reagent to ketimines for the preparation of such amines. The reaction of (Z)-3-substituted-2-propenyl carbonate with amines gave (Z)-linear amines with up to 100% selectivity. In all cases, no (E)-linear amine was obtained. The selectivities described here have not been achieved in similar palladium complex-catalyzed reactions.
- Takeuchi,Ue,Tanabe,Yamashita,Shiga
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p. 9525 - 9534
(2007/10/03)
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- Palladium-catalysed nucleophilic release of allylic amines from a phenolic resin
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2° Allylic alcohols were coupled to phenolic polystyrene resin under Mitsunobu conditions to provide substituted allyl ethers, which underwent efficient nucleophilic cleavage by 1° and 2° amines in the presence of catalytic palladium to afford allylic amines.
- Fisher, Martyn,Brown, Richard C.D
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p. 8227 - 8230
(2007/10/03)
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- A single step reductive amination of carbonyl compounds with polymethylhydrosiloxane-Ti(O(i)Pr)4
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Highly chemoselective 'one pot' amination of carbonyl groups is achieved using polymethylhydrosiloxane (PMHS) as reductant and Ti(O(i)Pr)4 as activator. A comparative study with other activators such as AlCl3 and Pd-C was also studied.
- Chandrasekhar,Reddy,Ahmed
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p. 1655 - 1657
(2007/10/03)
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- Superior performance of a chiral catalyst confined within mesoporous silica
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A chiral catalyst from the ligand 1,1'-bis(diphenylphosphino)ferrocene (dppf) anchored to the inner walls of the mesoporous support MCM-41 and co-ordinated to Pd(II) has been shown to exhibit a degree of regioselectivity and enantiomeric excess, in the allylic amination of cinnamyl acetate, which is far superior to that of its homogeneous counterpart or that of a surface-bound analogue attached to a non-porous silica.
- Johnson, Brian F. G.,Raynor, Stuart A.,Shephard, Douglas S.,Mashmeyer, Thomas,Thomas, John Meurig,Sankar, Gopinthar,Bromley, Stefen,Oldroyd, Richard,Gladden, Lynn,Mantle, Mike D.
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p. 1167 - 1168
(2007/10/03)
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- Inhibitors of squalene synthase and protein farnesyltransferase
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The present invention provides a compound of the formula STR1 or a pharmaceutically acceptable salt thereof, which are useful for inhibiting protein farnesyltransferase and the farnesylation of the oncogene protein Ras or inhibiting de novo squalene production resulting in the inhibition of cholesterol biosynthesis, processes for the preparation of the compounds of the invention in addition to intermediates useful in these processes, a pharmaceutical composition, and to methods of using such compounds.
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- Amination of(η3-allyl)dicarbonylnitrosyliron complexes: A route to γ- amino-α,β-unsaturated carboxylic acid derivatives
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Amines reacted regioselectively with (ν3-allyl)dicarbonylnitrosyliron complexes having ester group on the allyl ligand to give γ-amino-α,β- unsaturated esters in high yields. A remarkable effect of the substituents attached to the allyl ligand was observed on the reaction rate and regioselectivity of the amination. The methoxycarbonyl group significantly accelerates the reaction rate and enhances the regioselectivity of the reaction. The phenyl group retards the reaction, but enhances the regioselectivity, while alkyl groups retard the reaction and diminish the regioselectivity.
- Nakanishi, Saburo,Okamoto, Kenji,Yamaguchi, Hiroshi,Takata, Toshikazu
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p. 1735 - 1741
(2007/10/03)
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- Novel Tandem Conjugate Addition-Ramberg-B?cklund Rearrangements
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A novel tandem process is reported for the preparation of allylic amines, ethers and sulfides from α-bromo-α,β-unsaturated sulfones; this process is believed to proceed via an initial conjugate addition followed by proton exchange and Ramberg-Ba?cklund rearrangement.
- Evans, Paul,Taylor, Richard J. K.
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p. 1043 - 1044
(2007/10/03)
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- Trichlorosilane-dimethylformamide (Cl3SiH-DMF) as an efficient reducing agent. Reduction of aldehydes and imines and reductive amination of aldehydes under mild conditions using hypervalent hydridosilicates
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Trichlorosilane-dimethylformamide (Cl3SiH-DMF) was found to be an effective reducing agent for reduction of aldehydes to alcohols, imines to amines, and also reductive amination of aldehydes. Hypervalent silicates are active species, which enable efficient reduction under mild conditions.
- Kobayashi, Shu,Yasuda, Masaru,Hachiya, Iwao
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p. 407 - 408
(2007/10/03)
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- Reductive amination of aldehydes and ketones with sodium triacetoxyborohydride. Studies on direct and indirect reductive amination procedures
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Sodium triacetoxyborohydride is presented as a general reducing agent for the reductive amination of aldehydes and ketones. Procedures for using this mild and selective reagent have been developed for a wide variety of substrates. The scope of the reaction includes aliphatic acyclic and cyclic ketones, aliphatic and aromatic aldehydes, and primary and secondary amines including a variety of weakly basic and nonbasic amines. Limitations include reactions with aromatic and unsaturated ketones and some sterically hindered ketones and amines. 1,2-Dichloroethane (DCE) is the preferred reaction solvent, but reactions can also be carried out in tetrahydrofuran (THF) and occasionally in acetonitrile. Acetic acid may be used as catalyst with ketone reactions, but it is generally not needed with aldehydes. The procedure is carried out effectively in the presence of acid sensitive functional groups such as acetals and ketals; it can also be carried out in the presence of reducible functional groups such as C-C multiple bonds and cyano and nitro groups. Reactions are generally faster in DCE than in THF, and in both solvents, reactions are faster in the presence of AcOH. In comparison with other reductive amination procedures such as NaBH3CN/MeOH, borane-pyridine, and catalytic hydrogenation, NaBH(OAc)3 gave consistently higher yields and fewer side products. In the reductive amination of some aldehydes with primary amines where dialkylation is a problem we adopted a stepwise procedure involving imine formation in MeOH followed by reduction with NaBH4.
- Abdel-Magid, Ahmed F.,Carson, Kenneth G.,Harris, Bruce D.,Maryanoff, Cynthia A.,Shah, Rekha D.
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p. 3849 - 3862
(2007/10/03)
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- N-Benzyltriflamide: a Generally Useful Mitsunobu Reagent for Amine Synthesis
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N-Benzyl triflamide has been found to be generally useful as a Mitsunobu nucleophile for the preparation of a range of primary and secondary benzylamines from the corresponding alcohols, using the standard reagents DEAD and triphenylphosphine.
- Kathryn, E. Bell,Knight, David W.,Gravestock, Michael B.
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p. 8681 - 8684
(2007/10/02)
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- Metallic bismuth and tantalum mediated C-allylation of aldimines with allyl bromide
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A facile method for the synthesis of homoallyl amines using Bi/BU4NBr/MeCN and Ta/Bu4NBr/ THF system has been performed in a regiospecific manner.
- Bhuyan, Pulak J.,Prajapati, Dipak,Sandhu, Jagir S.
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p. 7975 - 7976
(2007/10/02)
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- Synthesis of Secondary Allylic Amines
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Secondary allylic amines were synthesized from aldehydes and primary amines via successive conversion into aldimines, α-haloaldimines and α,β-unsaturated aldimines, the latter being selectively reduced by sodium borohydride at the imino function.This method allowed the synthesis of secondary allylic amines with high preponderance of the E-stereochemistry.A comparison was made with an alternative method involving the generation of α,β-unsaturated aldimines from α,β-unsaturated aldehydes and primary amines, and subsequent borohydride reduction.
- Kimpe, Norbert de,Stanoeva, Elena,Verhe, Roland,Schamp, Niceas
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p. 587 - 592
(2007/10/02)
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