- Novel asymmetric catalytic nucleophilic fluorine heterocyclization reaction system and application thereof in chiral non-natural amino acid module synthesis
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The invention discloses a novel asymmetric catalytic fluorine heterocyclization reaction system and application thereof. The novel asymmetric catalytic fluorine heterocyclization reaction system provided by the invention comprises a chiral iodine catalyst and etherified boron trifluoride, and is applied to a catalytic asymmetric nucleophilic fluorine heterocyclization reaction of unsaturated amide; a fluoro oxazine derivative is obtained through treatment after the reaction; and the obtained fluoro oxazine derivative is subjected to hydrolysis and oxidation reaction to obtain the chiral non-natural amino acid. The reaction system provided by the invention has the following advantages: etherified boron trifluoride is used as a fluorine reagent, is cheap and easy to obtain, and has good stability and low toxicity; the reaction conditions are mild; the chiral iodine catalyst is simple to prepare and does not need a complex ligand; the system is environment-friendly and free of heavy metal pollution and precious metal waste; the obtained product is a fluoro oxazine derivative active molecular structure unit with two chiral centers; chiral non-natural amino acid can be obtained through conversion reaction of the product; and the chemical selectivity and stereoselectivity of the reaction are good, and the yield and optical purity are high.
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- Functionalization of (2S)-Isopropyl-5-iodo-2,3-dihydro-4(H)-pyrimidin-4- ones by a Suzuki-Miyaura Cross-Coupling Reaction Using Aryltrifluoroborate Salts: Convenient Enantioselective Preparation of α-Substituted β-Amino Acids
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A simple protocol for the Pd(OAc)2-catalyzed cross-coupling reaction of 1-benzoyl-(2S)-isopropyl-5-iodo-2,3-dihydro-4(H)-pyrimidin-4-ones with potassium aryltrifluoroborates was developed. The reaction is performed at 110°C with a ligand-free catalyst. In all cases, complete conversion of the 1-benzoyl-(2S)-isopropyl-5-iodo-2,3-dihydro-4(H)-pyrimidin-4-onesand aryltrifluoroborates into the C-C coupling products was observed within 30-360 min. It is noteworthy that a largevariety of groups present in the potassium aryltrifluoroborates (-CF3, -OMe, -SEt, -CN, -CHO, -Cl, -Cbz, -NCbz,-OH, -CO2H) could be tolerated. Hydrogenation of the endocyclic double bonds in the Suzuki-Miyaura products followed by acid hydrolysis afforded highly enantioenrichedα-aryl-substituted β-amino acids. We present a general approach for the synthesis of (2S)-isopropyl-5-aryl-2,3- dihydro-4(H)-pyrimidin-4-ones by Suzuki-Miyaura reaction of aryltrifluoroborate salts with(2S)-isopropyl-5-iodo-2,3-dihydro-4(H)-pyrimidin-4-ones in the presence of a palladium catalyst and a base. The arylated compounds were transformed into enantioenriched α-aryl-substituted β-amino acids. Copyright
- Stefani, Helio A.,Amaral, Monica F. Z. J.,Reyes-Rangel, Gloria,Vargas-Caporali, Jorge,Juaristi, Eusebio
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experimental part
p. 6393 - 6403
(2011/02/21)
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- Organocatalytic asymmetric transferhydrogenation of β-nitroacrylates: Accessing β2-amino acids
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We describe a highly efficient and enantioselective Hantzsch ester mediated conjugate reduction of β-nitroacrylates that is catalyzed by a Jacobsen thiourea catalyst as a key step in a new route to optically active β2-amino acids. Copyright
- Martin, Nolwenn J. A.,Cheng, Xu,List, Benjamin
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supporting information; experimental part
p. 13862 - 13863
(2009/02/06)
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- Asymmetric synthesis of β2-amino acids: 2-substituted-3-aminopropanoic acids from N-acryloyl SuperQuat derivatives
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Conjugate addition of lithium dibenzylamide to (S)-N(3)-acryloyl-4- isopropyl-5,5-dimethyloxazolidin-2-one (derived from l-valine) and alkylation of the resultant lithium β-amino enolate provides, after deprotection, a range of (S)-2-alkyl-3-aminopropanoic acids in good yield and high ee. Alternatively, via a complementary pathway, conjugate addition of a range of secondary lithium amides to (S)-N(3)-(2′-alkylacryloyl)-4-isopropyl-5,5- dimethyloxazolidin-2-ones, diastereoselective protonation with 2-pyridone, and subsequent deprotection furnishes a range of (R)-2-alkyl- and (R)-2-aryl-3-aminopropanoic acids in good yield and high ee. Additionally, the boron-mediated aldol reaction of β-amino N-acyl oxazolidinones is a highly diastereoselective method for the synthesis of a range of β-amino- β′-hydroxy N-acyl oxazolidinones. The Royal Society of Chemistry.
- Beddow, James E.,Davies, Stephen G.,Ling, Kenneth B.,Roberts, Paul M.,Russell, Angela J.,Smith, Andrew D.,Thomson, James E.
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p. 2812 - 2825
(2008/03/12)
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- Catalytic enantioselective synthesis of β2-amino acids
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A very direct approach for the synthesis of β-amino esters is provided by catalytic asymmetric C-H activation by means of carbenoid-induced C-H insertion (see scheme; Boc = butyloxycarbonyl; TFA = trifluoroacetic acid). The reactions described herein represent the first regioselective intermolecular C-H insertions occurring at a methyl site.
- Davies, Huw M. L.,Venkataramani, Chandrasekar
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p. 2197 - 2199
(2007/10/03)
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- New synthesis of enantiomerically pure (S)-3-amino-2-phenyl propanoic acid via the asymmetric transformation of its racemic N-phthaloyl derivative
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The synthesis of racemic N-phthalyl 3-amino-2-phenyl propanoic acid and its asymmetric transformation via the corresponding prochiral ketene have been investigated, allowing the preparation of enantiomerically pure (S)-3- amino-2-phenyl propanpic acid.
- Calmes, Monique,Escale, Francoise
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p. 2845 - 2850
(2007/10/03)
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- Stereochemical Studies on Aromatic Amino-acids. Part 4. Absolute Configuration of 3-Amino-2-phenylpropionic Acid
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(+)-3-Amino-2-phenylpropionic acid (1) was assigned the (S)-configuration by chemical correlation with (+)-(S)-1-amino-2-phenylbutane (2).O.r.d. and molecular rotation data for this amino-acid and various derivatives are reported and discussed in the light of well known rules which have been applied to α-amino-acids previously.
- Garbarino, Juan A.,Nunes, Oswaldo
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p. 906 - 908
(2007/10/02)
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