- Double Stereodifferentiation in the Asymmetric Dihydroxylation of Optically Active Olefins
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A study of the stereochemical control on the asymmetric dihydroxylation of the double bond of optically active vinyl epoxides and their derivatives (bromo derivatives, azido derivatives, and vinyl aziridines) was carried out and the obtained results are herein reported. The most interesting results were obtained on trans α,β-unsaturated epoxy esters, which were successfully converted with a diastereomeric ratio >80% into the corresponding diols using either the matched or the mismatched conditions, depending on the ligand used. Unprotected bromo derivatives and unprotected aziridines did not afford significant results, while for the protected bromo derivatives, azido derivatives, and N-Boc protected aziridines the matched conditions led to a diastereomeric ratio >95%. Chirality 28:387–393, 2016.
- Righi, Giuliana,Bovicelli, Paolo,Tirotta, Ilaria,Sappino, Carla,Mandic’, Emanuela
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Read Online
- Lithium diisopropylamide-mediated reactions of imines, unsaturated esters, epoxides, and aryl carbamates: Influence of hexamethylphosphoramide and ethereal cosolvents on reaction mechanisms
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Several reactions mediated by lithium diisopropylamide (LDA) with added hexamethylphosphoramide (HMPA) are described. The N-isopropylimine of cyclohexanone lithiates via an ensemble of monomer-based pathways. Conjugate addition of LDA/HMPA to an unsaturated ester proceeds via diand tetra-HMPA-solvated dimers. Deprotonation of norbornene epoxide by LDA/HMPA proceeds via an intermediate metalated epoxide as a mixed dimer with LDA. Ortholithiation of an aryl carbamate proceeds via a mono-HMPA-solvated monomer-based pathway. Dependencies on THF and other ethereal cosolvents suggest that secondary-shell solvation effects are important in some instances. The origins of the inordinate mechanistic complexity are discussed.
- Ma, Yun,Collum, David B.
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- Catalytic hydrogenation of α,β-unsaturated carboxylic acid derivatives using copper(i)/N-heterocyclic carbene complexes
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A simple and air-stable copper(i)/N-heterocyclic carbene complex enables the catalytic hydrogenation of enoates and enamides, hitherto unreactive substrates employing homogeneous copper catalysis and H2 as a terminal reducing agent. This atom economic transformation replaces commonly employed hydrosilanes and can also be carried out in an asymmetric fashion.
- Zimmermann, Birte M.,Kobosil, Sarah C. K.,Teichert, Johannes F.
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supporting information
p. 2293 - 2296
(2019/02/27)
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- General [4 + 1] Cyclization Approach to Access 2,2-Disubstituted Tetrahydrofurans Enabled by Electrophilic Bifunctional Peroxides
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A general [4 + 1] cyclization reaction of carbonyl nucleophiles with 2-iodomethylallyl peroxides, which function as unique electrophilic oxygen synthons, for the synthesis of a broad range of 2,2-disubstituted tetrahydrofurans is achieved under operationally simple conditions. The unprecedented asymmetric version of such reaction is also realized via chiral auxiliary-assisted cyclization, thus providing a distinct approach to access chiral tetrahydrofurans with high diastereoselectivities. The new method can be applied to the synthesis of core structure of posaconazole drug.
- Gao, Min,Zhao, Yukun,Zhong, Chen,Liu, Shengshu,Liu, Pengkang,Yin, Qi,Hu, Lin
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supporting information
p. 5679 - 5684
(2019/08/01)
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- Manganese-catalyzed oxophosphorylation reaction of carbon–carbon double bonds using molecular oxygen in air
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A novel aerobic manganese-catalyzed oxophosphorylation reaction of carbon–carbon double bonds of styrene derivatives and vinyl ethers using diethyl H-phosphonates was developed. This direct transformation of alkenes to β-ketophosphonate readily proceeded at room temperature via the direct incorporation of molecular oxygen present in air (open flask).
- Yamamoto, Daisuke,Ansai, Hiromasa,Hoshino, Junichi,Makino, Kazuishi
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p. 873 - 879
(2018/09/10)
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- PROCESS FOR THE MANUFACTURE OF (E)-4-N,N-DIALKYLAMINO CROTONIC ACID IN HX SALT FORM AND USE THEREOF FOR SYNTHESIS OF EGFR TYROSINE KINASE INHIBITORS
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The present invention is directed to an efficient process for the manufacture of (E)-4-N,N- dialkylamino crotonic acid in HX salt form of formula I, wherein R1 and R2 independently denote C1-3-alkyl groups and Xˉ denotes an acid anion, such as the chloride, bromide, tosylate, mesylate or trifluoroacetate anion, with high quality, and a process for synthesis of EGFR tyrosine kinase inhibitors with heterocyclic quinazoline, quinoline or pyrimidopyrimidine core structure, using the acid addition salt I and activated derivatives thereof as intermediates.
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Page/Page column 17
(2015/07/16)
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- PROCESS FOR THE MANUFACTURE OF (E)-4-N,N-DIALKYLAMINO CROTONIC ACID IN HX SALT FORM AND USE THEREOF FOR SYNTHESIS OF EGFR TYROSINE KINASE INHIBITORS
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The present invention is directed to an efficient process for the manufacture of (E)-4-N,N-dialkylamino crotonic acid in HX salt form of formula I wherein R1 and R2 independently denote C1-3-alkyl groups and X? denotes an acid anion, such as the chloride, bromide, tosylate, mesylate or trifluoroacetate anion, with high quality, and a process for synthesis of EGFR tyrosine kinase inhibitors with heterocyclic quinazoline, quinoline or pyrimidopyrimidine core structure, using the acid addition salt I and activated derivatives thereof as intermediates.
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Paragraph 0039
(2015/07/15)
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- Asymmetric synthesis of Sedum alkaloids via lithium amide conjugate addition
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Conjugate addition of lithium (R)-N-allyl-N-(α-methylbenzyl)amide or lithium (R)-N-but-3-enyl-N-(α-methylbenzyl)amide to an alkyl hexa-2,4-dienoate or alkyl hepta-2,6-dienoate, followed by ring-closing metathesis of the olefin functionalities within the resultant β-amino ester, generates a range of diastereoisomerically pure azacycles in good yield. These homochiral templates are readily transformed to a range of piperidine alkaloids of the Sedum family, and the corresponding five-, seven- and eight-membered ring homologues.
- Davies, Stephen G.,Fletcher, Ai M.,Roberts, Paul M.,Smith, Andrew D.
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experimental part
p. 10192 - 10213
(2010/02/28)
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- Selective esterifications of alcohols and phenols through carbodiimide couplings
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Esterification of carboxylic acids capable of forming ketene intermediates upon treatment with carbodiimides permits the selective acylation of alcohols in the presence of phenols lacking strong electron-withdrawing groups. The selectivity of acylations involving highly acidic phenols could be reversed through the addition of catalytic amount of acid. Esterification of other carboxylic acids was found to proceed through the formation of symmetric anhydrides and provide the opposite chemoselectivity. In both cases the relative acylation rates of substituted phenols are consistent with a reaction mechanism involving an attack of phenolate anions on electrophilic intermediates such as ketenes and symmetric anhydrides, with the carbodiimides serving both as an activating reagent and as a basic catalyst.
- Shelkov, Rimma,Nahmany, Moshe,Melman, Artem
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p. 397 - 401
(2007/10/03)
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- Acylation through ketene intermediates
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Carboxylic acids possessing a strong electron-withdrawing group in the α-position undergo facile dehydration upon reaction with carbodiimides to form the corresponding substituted ketenes that can react in situ with alcohols providing esters in a high yield. The ketene formed by the treatment of ethyl 2-methylmalonate with DCC was trapped in situ by a [4+2] cycloaddition with a second DCC molecule. The chemoselectivity of the acylation through the ketene intermediates was found to be substantially different from that of conventional acylation reagents showing a very low sensitivity toward the steric bulk of alcohols. A comparison of the sensitivity of the acylation to the steric bulk of alcohols supports the presence of a pseudopericyclic pathway for the nucleophilic addition of alcohols to ketenes derived from ethyl malonic and diethylphosphonoacetic acid.
- Shelkov, Rimma,Nahmany, Moshe,Melman, Artem
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p. 8975 - 8982
(2007/10/03)
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- Facile acylation of sterically hindered alcohols through ketene intermediates
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Figure presented Carboxylic acids possessing strongly electron withdrawing substituents in the α-position in the presence of DCC acylate sterically hindered and chemically sensitive alcohols. The pattern of reactivity, the deuteration experiments, and the formation of a product derived from a [4 + 2] cycloaddition reaction corroborate the existence of ketene intermediates in the reaction.
- Nahmany, Moshe,Melman, Artem
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p. 3733 - 3735
(2007/10/03)
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- Solid-phase synthesis of peptide isosters by nucleophilic reactions with N-terminal peptide aldehydes on a polar support tailored for solid-phase organic chemistry
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A new concept for the solid-phase synthesis of various peptide isosters as potential protease inhibitors is presented. An N-terminal peptide aldehyde was generated on the solid phase by the periodate cleavage reaction. The reactive aldehyde was characterized by MAS NMR on the solid phase and employed as a versatile starting material for various nucleophilic reactions. The reactions conducted include reductive amination, nitroaldol reaction, and the addition of ylides of the Horner-Wadsworth-Emmons type. Furthermore, the addition of silyl-stabilized carbanions and reactions with organo-metallics of lithium, copper, and zinc were investigated. All solid-phase reactions were carried out on a novel polar resin based on polyethylene glycol tailored for solid-phase organic chemistry. The synthesis and characterization of this resin is presented. Finally, the synthesis of elongated peptide isosters and the preparation of pseudosymmetric peptide isosters is demonstrated.
- Rademann, J?rg,Meldal, Morten,Bock, Klaus
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p. 1218 - 1225
(2007/10/03)
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- An enantioselective synthesis of (-)-indolizidine 167B, a skin alkaloid from a neotropical dendrobatid frog
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An enantioselective synthesis of (-)-indolizidine 167B 1, a neurotoxic constituent of the skins of neotropical frogs of the genus Dendrobates, has been achieved. Control of the absolute stereochemistry at C-5 resulted from an exceptionally stereoselective
- Michael, Joseph R.,Gravestock, David
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p. 146 - 157
(2007/10/03)
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- Steric and Electronic Effects on the Photochemical Reactivity of Oxime Acetates of β,γ-Unsaturated Aldehydes
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A general synthesis of 5-unsubstituted N-acetoxy 3,3-dimethyl-1-azapenta-1,4-dienes starting from 2-(1,3-dithian-2-yl)-2-methylpropanal is described.The influence of 5-phenyl, 4-phenyl, 5-cyclohexyl, 5-tert-butoxycarbonyl and 5,5-dicyclohexyl substitution on the outcome of the photochemical reactions of the oxime acetates of β,γ-unsaturated aldehydes has been studied with a view to proving or disproving the operation of a deactivating free rotor in the aza-di-?-methane rearrangement.The results obtained show that if the radical formed at C-5 can be stabilized by conjugation with an aryl group or by certain types of disubstitution then the aza-di-?-methane rearrangement takes place successfully.In any other situation the reaction fails.These results clearly show that the free rotor effect is not responsible for the failure of C-5 monosubstituted 1-aza-1,4-dienes to undergo the aza-di-?-methane rearrangement.
- Armesto, Diego,Horspool, William M.,Gallego, Mar G.,Agarrabeitia, Antonia R.
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p. 163 - 170
(2007/10/02)
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- Synthesis of Dialkyl Alkoxycarbonylmethanephosphonates (Alkyl Dialkoxyphosphinylacetates) using Phase-Transfer Catalysis
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A facile method for the preparation of dialkyl alkoxycarbonylmethanephosphonates under phase-transfer catalysis is described.
- Ye, Wezhen,Liao, Xiugao
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p. 986 - 988
(2007/10/02)
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