- Enantioselective and Diastereoselective Construction of Chiral Amino Alcohols by Iridium-f-Amphox-Catalyzed Asymmetric Hydrogenation via Dynamic Kinetic Resolution
-
The iridium-f-amphox-catalyzed asymmetric hydrogenation of racemic α-amino β-unfunctionalized ketones proceeds via a DKR (dynamic kinetic resolution) process for the construction of various chiral N,N-disubstituted α-amino β-unfunctionalized alcohols in quantitative yields with excellent enantioselectivities and diastereoselectivities (all products >99% ee and >99:1 dr, TON up to 100 000). Importantly, this catalytic asymmetric hydrogenation with a DKR process provided a highly efficient and powerful synthetic strategy for the preparation of key chiral intermediates of the preclinical antitumor agent (S,S)-R116010.
- Wu, Weilong,You, Cai,Yin, Congcong,Liu, Yuanhua,Dong, Xiu-Qin,Zhang, Xumu
-
p. 2548 - 2551
(2017/05/24)
-
- Theoretical and Experimental Optimization of a New Amino Phosphite Ligand Library for Asymmetric Palladium-Catalyzed Allylic Substitution
-
A new library of modular amino phosphite ligands obtained in a few synthetic steps from enantiopure amino alcohols has been tested in asymmetric Pd-catalyzed allylic substitution. The modular ligand design is crucial to find highly selective catalysts for each substrate type using a wide range of C-, N-, and O-nucleophiles. A DFT study of the species responsible for the enantiocontrol was used to optimize the ligand structure. By selecting the ligand components, we were able to identify unprecedented catalytic systems that can create new chiral C-C, C-N, and C-O bonds in a variety of substrate types (hindered and unhindered) in high yields and enantioselectivities (ee values up to 99 %). Further studies on the Pd-π-allyl intermediates provided a deep understanding of the effect of ligand structure in the origin of enantioselectivity. Potential applications of the new Pd/amino phosphite catalysts were demonstrated by the practical synthesis of a range of chiral carbocycles by simple tandem reactions, with no loss of enantioselectivity.
- Magre, Marc,Biosca, Maria,Norrby, Per-Ola,Pàmies, Oscar,Diéguez, Montserrat
-
p. 4091 - 4107
(2015/12/26)
-
- Ephedrine- and pseudoephedrine-derived thioureas in asymmetric michael additions of keto esters and diketones to nitroalkenes
-
Ephedrine-derived bifunctional thioureas have been synthesized and applied as organocatalysts in Michael additions of 1,3-dicarbonyl compounds to nitroalkenes. Georg Thieme Verlag Stuttgart.
- Flock, Angelika Marie,Krebs, Anke,Bolm, Carsten
-
supporting information; experimental part
p. 1219 - 1222
(2010/08/20)
-
- 1,2-Aminothioethers Derived from Ephedrine and Pseudoephedrine: Heterobidentate Ligands for the Palladium-Catalysed Asymmetric Allylic Substitution Reaction
-
Heterobidentate sulfide-tertiary amine ligands incorporating 1,2-aminothioethers derived from ephedrine and pseudoephedrine have been prepared and used successfully in the palladium-catalysed asymmetric allylic substitution reaction, giving ees of up to 89 percent. The stereoelectronic effects operating in the reactions are discussed.
- Page, Philip C. Bulman,Heaney, Harry,Reignier, Serge,Rassias, Gerasimos A.
-
-
- Dynamic resolution of α-bromo-α-alkyl esters using N-methyl pseudoephedrine as a chiral auxiliary: Asymmetric syntheses of α-amino acid derivatives
-
N-Methyl pseudoephedrine mediated dynamic resolution of α-bromo-α-alkyl esters in nucleophilic substitution reaction has been investigated. Best results are obtained when α-bromo-α-alkyl esters 1, 4 and 5 are allowed to equilibrate before the addition of nucleophile. This simple epimerization-substitution sequence provides a practical protocol for asymmetric syntheses of α-amino acid derivatives 2, 7 and 8 up to 98:2 enantiomeric ratio.
- Lee, Sang-Kuk,Nam, Jiyoun,Yong, Sun Park
-
p. 790 - 792
(2007/10/03)
-
- The Reductive Cleavage of Cyclic Aminol Ethers to N,N-Dialkylamino-derivatives: Modifications to the Eschweiler-Clarke Procedure
-
The reductive cleavage of cyclic aminol ethers to give N-alkylamino-derivatives in very high yields can be achieved using chlorotrimethylsilane in the presence of sodium cyanoborohydride: in the case of cyclic aminol ethers derived from formaldehyde the Eschweiler-Clarke reaction can be carried out in formic acid heated under reflux in the absence of formaldehyde.
- Page, Philip C. Bulman,Heaney, Harry,Rassias, Gerasimos A.,Reignier, Serge,Sampler, Edward P.,Talib, Salem
-
p. 104 - 106
(2007/10/03)
-
- Facile inversion of configuration of N-Boc-β-aminoalcohols via S(N)2 cyclization to oxazolidinones
-
Oxazolidinones are obtained by the cyclization of mesylates derived from N-Boc-β-Aminoalcohols. Hydrolysis of the N-Boc-Oxazolidinones regenerates the protected aminoalcohols with inverted configuration at the hydroxy group. (C) 2000 Elsevier Science Ltd.
- Benedetti,Norbedo
-
p. 10071 - 10074
(2007/10/03)
-
- Enantioselective [2,3] sigmatropic rearrangement mediated by a butyllithium-chiral ligand complex
-
The first enantioselective [2,3] sigmatropic rearrangement of acyclic diprop-2-ynyl ethers and alkenyl benzyl ethers is achieved by a BuLi-chiral ligand complex.
- Manabe, Shino
-
p. 737 - 738
(2007/10/03)
-
- Reaction of alkyl sulfoxides and phenylphosphinic acid with amines. Alternative reagents for secondary amines N-alkylation
-
Phenylphosphinic acid and dialkylsulfoxides are found to be alternative reagents for respectively the reducing reagent (formic acid) and the alkylating reagent (aldehyde) currently used for secondary amines N-alkylation. Primary amines do not react with this system, but phenylglycine is decarboxilated to benzylamine.
- Chauvin
-
p. 1425 - 1428
(2007/10/02)
-
- TRICARBONYLCHROMIUM(0) PROMOTED STEREOSELECTIVE TRANSFORMATIONS OF EPHEDRINE AND PSEUDOEPHEDRINE DERIVATIVES
-
(-)-(1S,2S)-(N,O-Dimethylephedrine)tricarbonylchromium(0) (6) and (-)-(1S,2R)-(N,O-dimethylpseudoephedrine)tricarbonylchromium(0) (22) undergo completely stereoselective ortho deprotonation upon treatment with alkyllithium base, followed by addition of an electrophile.In both cases, exclusive remolval of the pro-(R)-ortho proton was confirmed by single X-ray structure analyses of the methylated products.Addition of methyllithium onto the ortho-formylated derivative of complex (6) occurs stereoselectively, the stereochemistry of the major product being confirmed by a single crystal X-ray structure determination.The results presented demonstrate an efficient transfer of chirality from a side chain onto the (arene)tricarbonylchromium(0) complex and back to a different side chain.
- Coote, Steven J.,Davies, Stephen G.,Goodfellow, Craig L.,Sutton, Kevin H.,Middlemiss, David,Naylor, Alan
-
p. 817 - 842
(2007/10/02)
-
- AUXILIARY SRTUCTURE AND ASYMMETRIC INDUCTION IN THE "MUKAIYAMA-ALDOL" REACTIONS OF CHIRAL SILYL KETENE ACETALS
-
A variety of chiral auxiliaries R*OH were prepared and tested for levels of asymmetric induction control in the "Mukaiyama-aldol" reaction of chiral silyl ketene acetals.Structural features required for high levels of control are discussed.
- Gennari, Cesare,Molinari, Francesco,Cozzi, PierGiorgio,Oliva, Ambrogio
-
p. 5163 - 5166
(2007/10/02)
-
- Fluoride Ion Catalyzed Reduction of Aldehydes and Ketones with Hydrosilanes. Synthetic and Mechanistic Aspects and an Application to the Threo-Directed Reduction of α-Substituted Alkanones
-
Reduction of aldehydes and ketones with hydrosilanes proceeded in the presence of a catalytic amount of tetrabutylammonium fluoride or tris(diethylamino)sulfonium difluorotrimethylsilicate in aprotic polar solvents under mild conditions.A significant isotope effect (kH/kD = 1.50) was observed in competitive reduction of acetophenone with HSiMe2Ph and DSiMe2Ph.The reaction was of first order in the concentration of an aprotic polar solvent HMPA.Reduction of 2-methylcyclohexanone gave cis-2-methylcyclohexanol with selectivities up to 95percent.The kinetic and stereochemical results suggest that a hexavalent fluorosilicate - is involved. α-Alkoxy (acyloxy or dimethylamino) ketones were transformed to threo alcohols in high diastereoselectivities.The reduction was also applied to α-methyl-β-keto amides, RCOCH(MeCONR)2, to afford the corresponding threo alcohols in >98percent selectivity.The threo selectivity is explained in terms of the Felkin-Anh model in which interaction of carbonyl oxygen with a countercation is ideally suppressed.The threo-directed reduction was applied to (R)-1-phenyl-4-(2-tetrahydropyranyloxy)-1-penten-3-one and N-(2-benzoylpropanoyl)piperidine.The resulting threo alcohols were respectively converted into (2R,3S)-2,3-(cyclohexylidenedioxy)butanal, a key intermediate of daunosamine synthesis, and into a pharmacologically useful compound threo-N-(3-hydroxy-2-methyl-3-phenylpropyl)piperidine.
- Fujita, Makoto,Hiyama, Tamejiro
-
p. 5405 - 5415
(2007/10/02)
-
- THE HIGHLY STEREOSELECTIVE CONVERSION OF N,N-DIMETHYLAMPHETAMINE INTO N-METHYLPSEUDOEPHEDRINE; A MIMIC OF THE ENZYME MEDIATED STEREOSPECIFIC BENZYLIC HYDROXYLATION OF 2-ARYLETHYLAMINES
-
Treatment of (S)-(η6-N,N-dimethylamphetamine)Cr(CO)3, with n-butyllithium below -40 deg C gives a stable benzylic carbanion via loss of the pro-R-benzylic proton.Warming of this anion above -40 deg C gives (η6-E-β-methylstyrene)Cr(CO), via an ElcB type elimination wilhst trapping with an electrophile below -40 deg C gives benzylically functionalised amphetamines with overall retention of configuration.The use of oxodiperoxymolybdenum(pyridine)hexamtehylphosphoramide as the electrophile gives optically pure (1S,2S)-N-methylpseudoephedrine after decomplexation.
- Blagg, Julian,Davies, Stephen G.
-
p. 4463 - 4472
(2007/10/02)
-
- Sur la stereochimie de la reduction des aminocetones et des aziridinocetones par le borohydrure de zinc
-
The reduction of aminoketones and aziridinoketones with zinc borohydride is highly stereoselective.The zinc atom is complexed only by nitrogen atoms of reduced molecules.There is no chelate formation with the participation of carbonyl groups.
- Bartnik, Romuald,Eddaif, A.,Laurent, A.,Lesniak, Stanislaw
-
-
- Kinetic Resolution of Racemic β-Hydroxy Amines by Enantioselective N-Oxide Formation
-
A practical and fairly general procedure for the kinetic resolution of β-hydroxy tertiary amines is described.It involves the selective oxidation of one enantiomer to the N-oxide by using tert-butyl hydroperoxide (TBHP) and a chiral catalyst prepared by mixing 2 parts of titanium isopropoxide (Ti(O-i-Pr)4 and 1.2 parts of either (+)- or (-)-diisopropyl tartrate (DIPT).The product N-oxide and the unreacted amino alcohol are then easily separated by trituration or organic/aqueous solvent extractions, and chromatography is avoided.The oxidations are generally run to 60percent conversion and the results for 21 different amino alcohols are given.The enantiomeric excess of the slow reacting (i.e., recovered) enantiomer of the amino alcohol often exceeds 90percent.Among the more interesting substrates are the natural product ubine (95percent ee) (18), N-methylephedrine (95percent ee) (15), N-methylpseudoephedrine (93percent ee) (16), cis-2-(dimethylamino)cyclohexanol (>95percent ee) (13), trans-2-(dimethylamino)cyclohexanol (92percent ee) (12), N-benzylbevantolol (85percent ee) (27), and N-benzylpropranolol (32percent ee) (21).The latter two examples are β-blocker precursors.One of the most important characteristics of this new route to enantiomerically pure β-hydroxy amines is its predictability.Thus, in all cases examined to date, when using (+)-DIPT the absolute configuration at the carbinol center in the slow reacting enantiomer is always the same .A study of how the titanium/tartrate ratio, water, catalyst/substrate ratio, and temperature effect this reaction is discussed.
- Miyano, Sotaro,Lu, Linda D.-L.,Viti, Steven M.,Sharpless, K. Barry
-
p. 4350 - 4360
(2007/10/02)
-
- Stereospecific Conversion of N,N-Dimethylamphetamine into N-Methylpseudoephedrine
-
The pro-R hydrogen of (+)-N,N-dimethylamphetamine chromium tricarbonyl can be stereospecifically substituted via sequential treatment with BunLi and an electrophile, with retention of configuration to give for example N-methylpseudoephedrine after decomplexation.
- Blagg, Julian,Davies, Stephen G.
-
p. 653 - 654
(2007/10/02)
-
- Ueber die Enantiomerentrennung durch Verteilung zwischen fluessigen Phasen 3. Mitteilung. Selektivitaet der lipophilen Weinsaeureester fuer chirale Ammonium-Salze verschiedener Konstitution und Konfiguration
-
Several methods are described which allow determination on a small scale of the enantiomer distribution constant Q, and the affinity coefficient P, which characterize the enantioselectivity and the affinity of a lipophilic phase for ammonium salts of different constitution and configuration.The influence of concentration of the tartaric acid ester, temperature, concentration and type of the lipophilic anion on Q and P was investigated to find out favourable experimental conditions for resolutions of racemates by iterative processes, e.g. partition chromatography.The relation ship between Q and the configuration of aminoalcohols 1-12 was explored and the observed regularities are pointed out.In addition it was found that lipophilic tartaric acid esters are enantioselective to salts of threo-1,2-diphenyl-1,2-ethanediamine 13, and to phenylglycine and its derivatives 14-16.
- Prelog, Vladimir,Mutak, Stjepan,Kovacevic, Krunoslav
-
p. 2279 - 2284
(2007/10/02)
-
- Kinetic Resolution of Racemic β-Hydroxy Amines by Enantioselective N-Oxide Formation
-
Enantioselective oxidation using TBHP and an asymmetric titanium-tartrate complex provides direct access to a variety of homochiral β-hydroxy amines.
- Miyano, Sotaro,Lu, Linda D.-L.,Viti, Steven M.,Sharpless, K. Barry
-
p. 3608 - 3611
(2007/10/02)
-