- Design of a genetic algorithm for the simulated evolution of a library of asymmetric transfer hydrogenation catalysts
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A library of catalysts was designed for asymmetric-hydrogen transfer to acetophenone. At first, the whole library was submitted to evaluation using high-throughput experiments (HTE). The catalysts were listed in ascending order, with respect to their performance, and best catalysts were identified. In the second step, various simulated evolution experiments, based on a genetic algorithm, were applied to this library. A small part of the library, called the mother generation (GO), thus evolved from generation to generation. The goal was to use our collection of HTE data to adjust the parameters of the genetic algorithm, in order to obtain a maximum of the best catalysts within a minimal number of gen-erations. It was namely found that simulated evolution's results depended on the selection of GO and that a random GO should be preferred. We also demonstrated that it was possible to get 5 to 6 of the ten best catalysts while investigating only 10% of the library. Moreover, we developed a double algorithm making this result still achievable if the evolution started with one of the worst GO.
- Vriamont, Nicolas,Govaerts, Bernadette,Grenouillet, Pierre,De Bellefon, Claude,Oliant, Olivier
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supporting information; experimental part
p. 6267 - 6278
(2010/01/19)
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- N-Pyridylmethylephedrine derivatives in the catalytic asymmetric addition of diethylzinc to aldehydes and diphenylphosphinoylimines
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N-Pyridylmethyl-substituted Ephedra derivatives were synthesized by either direct alkylation or reductive alkylation of (1R,2S)-norephedrine, (1S,2S)-pseudo norephedrine, and (1R,2S)-ephedrine. These derivatives were then employed in asymmetric addition reactions with diethylzinc and aldehydes and diphenylphosphinoylimines. The use of the diastereomers from the Ephedra family allowed for a systematic evaluation of the contribution of the N-pyridylmethyl.
- Banerjee, Sucharita,Groeper, Jonathan A.,Standard, Jean M.,Hitchcock, Shawn R.
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experimental part
p. 2154 - 2161
(2010/03/03)
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- Salicylaldehyde based oxazolidines as catalysts for the asymmetric addition of diethylzinc to aldehydes
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(Chemical Equation Presented) A series of oxazolidines have been prepared by condensation of N-isopropyl norephedrine with a variety of salicylaldehyde derivatives. Despite the stereochemical relationship of (1R,2S)-norephedrine with (1R,2S)-ephedrine, th
- Parrott II, Raleigh W.,Hamaker, Christopher G.,Hitchcock, Shawn R.
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p. 873 - 878
(2008/09/21)
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- β-Amino alcohols derived from (1R,2S)-norephedrine and (1S,2S)-pseudonorephedrine as catalysts in the asymmetric addition of diethylzinc to aldehydes
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A family of N-alkylnorephedrine and N-alkylpseudonorephedrine derived ligands were prepared and applied in the asymmetric alkylation of benzaldehyde using diethylzinc. The absolute configuration of the addition product was directed primarily by the benzylic position of the Ephedra alkaloid, while the magnitude of the enantiomeric ratio was heavily influenced by the nitrogen substituent. However, sterically demanding substituents at the nitrogen position caused the enantioselectivity to be the same for the two diastereomeric systems. Among the ligands that were prepared, it was determined that the N-cyclooctylpseudonorephedrine derivative 7b yielded the highest enantiomeric ratios (87.5:12.5 to 91.0:9.0) when applied in the catalytic asymmetric addition of diethylzinc to aldehydes.
- Parrott II, Raleigh W.,Hitchcock, Shawn R.
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- Diastereoselective reduction of α-aminoketones: Synthesis of anti- and syn-β-aminoalcohols
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Reduction of N-t-BOC-protected-N-alkyl α-aminoketones with LiEt 3BH or Li(S-Bu)3BH furnishes protected syn-β-aminoalcohols with high selectivities. In contrast, removal of the BOC group followed by reduction of the aminoketone gives anti-β- aminoalcohols with variable selectivities. With aromatic ketones, selectivities are typically high while aliphatic ketones show mediocre to high selectivities depending on steric considerations.
- Fraser, David S.,Park, Sheldon B.,Chong, J. Michael
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- Diastereoselectivity in the reduction of α-oxy- and α-amino-substituted acyclic ketones by polymethylhydrosiloxane
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Diastereoselectivity in the reduction of α-alkoxy-, α-acyloxy-, and α-alkylamino-substituted ketones with polymethylhydrosiloxane (PMHS) in the presence of fluoride ion catalysis was investigated. High syn-selectivity was observed in the reduction of α-alkoxy, α-acyloxy, and α-dialkylamino ketones. Reduction of α-monoalkylamino ketone proceeded in anti-selective manner with moderate selectivity. The observed selectivity is explained based on Felkin-Anh and Cram-chelate models.
- Nadkarni, Durgesh,Hallissey, James,Mojica, Carlos
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p. 594 - 596
(2007/10/03)
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- The use of benzamide derivatives of secondary amines for stereochemical studies by circular dichroism
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The benzamide chromophore is widely used as a Cottonogenic derivative of primary amines for stereochemical studies by circular dichroism. The assignments based on the exciton chirality method are reliable since the benzamide group has well-defined geometry and conformation. A recent report U.D. Chisholm, J. Golik, B. Krishnan, J.A. Matson, D.L. Van Vranken, J. Am. Chem. Soc. 1999, 121: 3801-3802) claimed a caveat in the application of the exciton chirality method to benzamides derived from secondary amines. By the use of benzoyl derivatives of amino alcohols (1-4) and diamines (5, 6) of known absolute configuration we demonstrate that the 250-210 nm range exciton Cotton effects due to secondary and tertiary benzamides are generally of opposite sign. The origin of such disparity is traced to different conformational equilibria of the amide C-N bond in secondary and tertiary benzamides, as shown by semiempirical molecular modelling and NMR data. This feature can be useful in the determination of absolute configuration by analysis of the CD spectra due to exciton coupling of tertiary benzamides.
- Gawronski, Jacek,Kolbon, Halina,Kwit, Marcin
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- Stereoselective synthesis of δ-lactones from 5-oxoalkanals via one-pot sequential acetalization, tishchenko reaction, and lactonization by cooperative catalysis of samarium ion and mercaptan
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By the synergistic catalysis of samarium ion and mercaptan, a series of 5-oxoalkanals was converted to (substituted) δ-lactones in efficient and stereoselective manners. This one-pot procedure comprises a sequence of acetalization, Tishchenko reaction and lactonization. The deliberative use of mercaptan, by comparison with alcohol, is advantageous to facilitate the catalytic cycle. The reaction mechanism and stereochemistry are proposed and supported by some experimental evidence. Such samarium ion/mercaptan cocatalyzed reactions show the feature of remote control, which is applicable to the asymmetric synthesis of optically active δ-lactones. This study also demonstrates the synthesis of two insect pheromones, (2S,5R)-2-methylhexanolide and (R)-hexadecanolide, as examples of a new protocol for asymmetric reduction of long-chain aliphatic ketones.
- Hsu,Fang
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p. 8573 - 8584
(2007/10/03)
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- PROCESS FOR PRODUCING L-ERYTHRO-(1R,2S)-2-AMINO-1-PHENYLPROPAN-1-OL
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An efficient process for stereoselectively producing L-erythro-(1R,2S)-2-amino-1-phenylpropan-1-ol from L-(R)-phenylacetylcarbinol, which comprises reductively aminating L-(R)-phenylacetylcarbinol with a primary aralkylamine under catalytic reduction conditions and successively subjecting the resultant L-erythro-(1R,2S)-2-(N-aralkylamino)-1-phenylpropan-1-ol to catalytic reduction to remove the N-aralkyl group in a manner as in hydrogenolysis.
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- Amino alcohol coordination in ruthenium(II)-catalysed asymmetric transfer hydrogenation of ketones
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The nature of ruthenium-amino alcohol precursors in the catalytic cycle of asymmetric hydrogen transfer reactions was studied using two C2- symmetrical tetradentate ligands (1 and 2) that were synthesised from (nor)ephedrine. The structure of t
- Petra, Danielle G. I.,Kamer, Paul C. J.,Van Leeuwen, Piet W. N. M.,Goubitz, Kees,Van Loon, Arjen M.,De Vries, Johannes G.,Schoemaker, Hans E.
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p. 2335 - 2341
(2007/10/03)
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- Phospho-transfer catalysis on the asymmetric hydrophosphonylation of aldehydes
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We report here a precise, in situ 31P{1H}-NMR method of assaying enantiopurity of α-hydroxyphosphonate esters, the products of the carbonyl hydrophosphonylation (Pudovik) reaction. This method is based upon a diazaphospholidine chiral derivatising agent (CDA) which satisfies all of the criteria for a precise assay; (i) derivatisation of α-hydroxyphosphonate esters is both rapid and clean, (ii) kinetic resolution is absent and (iii) 31P{1H} chemical shift dispersions are excellent (> 5ppm). Calibration of this assay has been achieved by cross-referencing the 31P{1H}-NMR signals obtained for the CDA-derivatised ester of (MeO)2PC=O)CHPh(OH) to optical rotation measurements from scalemic material obtained upon lipase catalysed hydrolysis (F-AP 15, Rhizopus oryzae) of (MeO)2P(=O)CHPh(OAc). Analysis of NMR chemical shift and coupling parameters for a closely related series of derivatised α-hydroxyphosphonate esters support further configuration assignments on the basis of inference. We report also on the configurational stability of α-hydroxyphosphonate esters in the presence of acids, organonitrogen bases and metal salts. 2H-labelling and carbonyl crossover experiments reveal that low levels of epimerisation (α) of α-hydroxyphosphonate esters is possible under certain conditions of catalysis and within certain limits. A design strategy for the construction of catalyst systems in the Pudovik reaction is outlined based upon a combination of Lewis acidic (E) and Lewis basic (N) sites. Four types of catalyst are outlined, members of two distinct Classes I and II according to the nature of the acid and base sites, along with our investigations of representative examples of each Class. A variety of Class I.1 systems based on β-amino alcohols (one hydrogen bonding E site and one organonitrogen N site), have been assayed in the model reaction between (MeO)2P(O)H and PhCHO. Results suggest that catalysis of the Pudovik reaction is clean and efficient in certain cases but that catalytic activity is strongly dependent upon the nature of the basic (N) nitrogen centre. Moreover, only low levels ( 50% more strongly (K11 0.53 mol-1 dm3) than dimethyl-H-phosphonate (K11 0.34 mol-1 dm3, 298 K) and to catalyse the hydrophosphonylation reaction between these two substrates with a second order rate constant comparable to that of triethylamine (both k2 5.9 × 10-2 mol-1 dm3 h-1, 293 K). However, one of the major limitations of this model is that competitive product inhibition dominates after some 15 turnovers (75% completion). Model studies reveal that hydrophosphonylation catalysis via a nitrogen Lewis base is accelerated up to 10-fold upon the introduction of [Zn(OSO2CF3)2] as co-catalyst. Consequently, Class II.1 systems employ metal salts [Zn(OSO2CF3)2] as Lewis acidic E sites and chiral co-catalysts capable of binding to the metal and also acting as Lewis basic N sites. Such systems catalyse the addition of (MeO)2P(O)H to PhCHO cleanly with modest turnover numbers (2P(O)H to PhCHO to afford (MeO)2P(O)CHPh(OH) with an average turnover rate (over a 1 h reaction time at 298 K) of 115 h-1 compared to ca. 1 h-1 for NEt3 under analogous conditions. Chiral variants are proposed.
- Davies, Stephen R.,Mitchell, Michael C.,Cain, Christopher P.,Devitt, Paul G.,Taylor, Roger J.,Kee, Terence P.
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- Stereoselective synthesis of (1R)- and (1R,2S)-1-aryl-2-alkylamino alcohols from (R)-cyanohydrins
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Hydrogenation of (R)-cyanohydrins (R)-1 with LiAlH4 occurs without racemization to give the (R)-2-amino alcohols (R)-3. (1R,2S)-2-Amino alcohols (1R,2S)-4 are obtained with high diastereoselectivity by addition of methyl Grignard to O-silyl protected cyanohydrins (R)-2 and subsequent hydrogenation with NaBH4. The N-alkylated 2-amino alcohols (R)-8 and (1R,2S)-9 can be prepared either by reductive alkylation of the corresponding 2-amino alcohols (R)-3 and (1R,2S)-4, respectively, or by a transimination reaction of the Grignard addition products with primary amines and subsequent hydrogenation with NaBH4. The lower diastereoselectivity of hydrogenation in case of the N-alkylmino compounds in comparison to the N-unsubstituted imines is explained by a weaker chelating effect.
- Effenberger, Franz,Gutterer, Beate,Jaeger, Juergen
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p. 459 - 467
(2007/10/03)
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- Preparation of 2-oxazolidinones by intramolecular nucleophilic substitution
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Treatment of N-alkoxycarbonyl, N-benzyl protected β-amino alcohols with triphenylphosphine and hexachloroethane in 1,2-dichloroethane induces cyclization to 2-oxazolidinones, which are formed by intramolecular attack with inversion of configuration at the secondary alcohol. In contrast, mono N-substituted alkyl carbamates undergo chlorination under the same conditions.
- Van Delft, Floris L.,Timmers, Cornelis M.,Van Der Marel, Gijs A.,Van Boom, Jacques H.
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p. 450 - 454
(2007/10/03)
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- Method for the preparation of erythro vicinal amino-alcohols
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The present invention is concerned with the preparation of erythro N-substituted vicinal aminoalcohol derivatives from hydroxyl-protected cyanohydrin derivatives by successive Grignard reaction, transimination using a primary amine, reduction of the resulting imine and removal of the hydroxyl-protecting group. The products are obtained either as a racemate or in an optically pure form, depending upon the stereochemical composition of the cyanohydrin derivatives.
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- Stereoselectrive Syntheses of Ephedrine and Related 2-Aminoalcohols of High Optical Purity from Protected Cyanohydrins
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Ephedrine and related optically active β-aminoalcohols can be prepared by zinc borohydride reduction of aryl O-protected magnesium imines and aryl α-hydroxyimimes which in turn are readily available from optically active cyanohydrins.
- Jackson, W. Roy,Jacobs, Howard A.,Matthews, Barry R.,Jayatilake, Gamini S.,Watson, Keith G.
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p. 1447 - 1450
(2007/10/02)
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- Applications of Optically Active Aryl Cyanohydrins in the Synthesis of α-Hydroxy Aldehydes, α-Hydroxy Ketones and β-Hydroxy Amines
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Cyanohydrins, prepared in high optical purity from aryl aldehydes, have been converted into α-hydroxy aldehydes, α-hydroxy ketones and β-hydroxy amines without any racemization and frequently with good stereoselectivity for the erythro-diastereoisomer (>90percent) at the newly introduced stereogenic centre.
- Jackson, W. Roy,Jacobs, Howard A.,Jayatilake, Gamini S.,Matthews, Barry R.,Watson, Keith G.
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p. 2045 - 2062
(2007/10/02)
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- Highly enantioselective photodeconjugation of α,β-unsaturated esters. Origin of the chiral discrimination
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The photodeconjugation of α-methyl conjugated esters can be highly enantioselective when carried out in CH2Cl2 or hexane in the presence of catalytic amounts of chiral β-amino alcohols. Enantiomeric excesses (ee %) up to 70% are desc
- Piva, Olivier,Mortezaei, Reza,Henin, Fran?oise,Muzart, Jacques,Pete, Jean-Pierre
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p. 9263 - 9272
(2007/10/02)
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