63401-04-7Relevant articles and documents
London Dispersion Interactions Rather than Steric Hindrance Determine the Enantioselectivity of the Corey–Bakshi–Shibata Reduction
Eschmann, Christian,Song, Lijuan,Schreiner, Peter R.
supporting information, p. 4823 - 4832 (2021/02/01)
The well-known Corey–Bakshi–Shibata (CBS) reduction is a powerful method for the asymmetric synthesis of alcohols from prochiral ketones, often featuring high yields and excellent selectivities. While steric repulsion has been regarded as the key director of the observed high enantioselectivity for many years, we show that London dispersion (LD) interactions are at least as important for enantiodiscrimination. We exemplify this through a combination of detailed computational and experimental studies for a series of modified CBS catalysts equipped with dispersion energy donors (DEDs) in the catalysts and the substrates. Our results demonstrate that attractive LD interactions between the catalyst and the substrate, rather than steric repulsion, determine the selectivity. As a key outcome of our study, we were able to improve the catalyst design for some challenging CBS reductions.
Preparation method of duloxetine
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Paragraph 0054-0059, (2021/09/26)
To the method, 1 - naphthol and 3 - (2 - thienyl) -2 - acrolein serve as starting materials, and (S)-3 - (1 - naphthyloxy) -3 - (2 - thienyl) propanal is obtained through addition reaction under the action of a catalyst. The raw materials are cheap and easily available, and 1 - fluoronaphthalene which is expensive is not needed. Sodium hydride and operation are tedious, the cost is low, the process operation is safe and convenient, the three wastes are small in generation amount, and green and environment-friendly. The reaction atom economy is high, the reaction selectivity of each step is high, the side reaction is small, the optical purity and yield of the target product are high, and the green industrial production is facilitated.
Basicities and Nucleophilicities of Pyrrolidines and Imidazolidinones Used as Organocatalysts
An, Feng,Maji, Biplab,Min, Elizabeth,Ofial, Armin R.,Mayr, Herbert
supporting information, p. 1526 - 1547 (2020/02/04)
The Br?nsted basicities pKaH (i.e., pKa of the conjugate acids) of 32 pyrrolidines and imidazolidinones, commonly used in organocatalytic reactions, have been determined photometrically in acetonitrile solution using CH acids as indicators. Most investigated pyrrolidines have basicities in the range 16 aH aH aH 12.6) and the 2-imidazoliummethyl-substituted pyrrolidine A21 (pKaH 11.1) are outside the typical range for pyrrolidines with basicities comparable to those of imidazolidinones. Kinetics of the reactions of these 32 organocatalysts with benzhydrylium ions (Ar2CH+) and structurally related quinone methides, common reference electrophiles for quantifying nucleophilic reactivities, have been measured photometrically. Most reactions followed second-order kinetics, first order in amine and first order in electrophile. More complex kinetics were observed for the reactions of imidazolidinones and several pyrrolidines carrying bulky 2-substituents, due to reversibility of the initial attack of the amines at the electrophiles followed by rate-determining deprotonation of the intermediate ammonium ions. In the presence of 2,4,6-collidine or 2,6-di-tert-butyl-4-methyl-pyridine, the deprotonation of the initial adducts became faster, which allowed the rate of the attack of the amines at the electrophiles to be determined. The resulting second-order rate constants k2 followed the correlation log?k2(20 °C) = sN(N + E), where electrophiles are characterized by one parameter (E) and nucleophiles are characterized by the two solvent-dependent parameters N and sN. In this way, the organocatalysts A1-A32 were integrated in our comprehensive nucleophilicity scale, which compares n-, -, and σ-nucleophiles. The nucleophilic reactivities of the title compounds correlate only poorly with their Br?nsted basicities.
Isosteric expansion of the structural diversity of chiral ligands: Design and application of proline-based N,N′-dioxide ligands for copper-catalyzed enantioselective Henry reactions
Gao, En,Li, Meng,Duan, Lili,Li, Lin,Li, Yue-Ming
, (2019/08/16)
Chiral N,N′-dioxide catalysts were designed based on isosteric approach. Using L-Proline as the starting material, a variety of chiral N,N′-dioxide ligands were obtained via conventional functional group transformations and were utilized in asymmetric Henry reactions between nitromethane and aromatic aldehydes. Using the N,N′-dioxide-copper(II) complexes as the catalysts, asymmetric Henry reaction produced the corresponding β-nitroalcohols in up to 66% yields and up to 83% ee's under mild conditions. The reactions were easy to carry out, and special care such as air or moisture-free conditions was not required.
Intramolecular [2+2] Photocycloaddition of Cyclic Enones: Selectivity Control by Lewis Acids and Mechanistic Implications
Poplata, Saner,Bauer, Andreas,Storch, Golo,Bach, Thorsten
supporting information, p. 8135 - 8148 (2019/05/29)
The intramolecular [2+2] photocycloaddition of 3-alkenyl-2-cycloalkenones was performed in an enantioselective fashion (nine representative examples, 54–86 % yield, 76–96 % ee) upon irradiation at λ=366 nm in the presence of an AlBr3-activated oxazaborolidine as the Lewis acid. An extensive screening of proline-derived oxazaborolidines showed that the enantioface differentiation depends strongly on the nature of the aryl group at the 3-position of the heterocycle. DFT calculations of the Lewis acid–substrate complex indicate that attractive dispersion forces may be responsible for a change of the binding mode. The catalytic [2+2] photocycloaddition was shown to proceed on the triplet hypersurface with a quantum yield of 0.05. The positive effect of Lewis acids on the outcome of a given intramolecular [2+2] photocycloaddition was illustrated by optimizing the key step in a concise total synthesis of the sesquiterpene (±)-italicene.
Synthesis process of chiral catalyst
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Paragraph 0090; 0091; 0094-0096; 0099-0101; 0102; 0105-0107, (2019/02/17)
The invention relates to a low-cost efficient synthesis process of both a chiral catalyst chiral (R)-(+)-2-(Diphenylhydroxymethyl)pyrrolidine and a hydrochloride thereof. According to the process, rawmaterials which can be commercially obtained easily and are environmentally friendly are used; a one-kettle method is used for operation; through esterification reaction, Boc protecting group addition on amino group, Grignard reaction and Boc protecting group removal, high-optical-purity (R)-(+)-2-(Diphenylhydroxymethyl)pyrrolidine hydrochloride is obtained. The process is simplified; the production cost is reduced; the requirements of green chemistry at present are met. The content of (R)-(+)-2-(Diphenylhydroxymethyl)pyrrolidine and the hydrochloride thereof, prepared by the process, is higher than 99.0 percent; the optical purity is not smaller than 99.5 percent; the total yield is higher than 80 percent.
COMPOUNDS, COMPOSITIONS AND METHODS FOR SYNTHESIS
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Paragraph 001345; 001346; 001349; 001350, (2019/01/10)
The present disclosure, among other things, provides technologies for synthesis, including reagents and methods for stereoselective synthesis. In some embodiments, the present disclosure provides compounds useful as chiral auxiliaries. In some embodiments, the present disclosure provides reagents and methods for oligonucleotide synthesis. In some embodiments, the present disclosure provides reagents and methods for chirally controlled preparation of oligonucleotides. In some embodiments, technologies of the present disclosure are particularly useful for constructing challenging internucleotidic linkages, providing high yields and stereoselectivity.
NITROGEN RING LINKED DEOXYURIDINE TRIPHOSPHATASE INHIBITORS
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Paragraph 0684, (2018/06/12)
Provided herein are dUTPase inhibitors, compositions comprising such compounds and methods of using such compounds and compositions.
Aluminium, gallium and indium complexes supported by a chiral phenolato-prolinolato dianionic ligand
Maudoux, Nicolas,Tan, Eric,Hu, Yuya,Roisnel, Thierry,Dorcet, Vincent,Carpentier, Jean-Fran?ois,Sarazin, Yann
, p. 131 - 143 (2016/12/14)
Congeneric complexes (S)-{?O}MCH2SiMe3 (M=Al, 3; Ga, 5; In, 6) of the triel metals supported by an enantiomerically pure phenolato-alkoxo {?O}2- dianionic tridentate ligand derived from prolinol, along with their chloro derivatives, have been prepared and characterised. The aluminium-alkyl species (S)-{?O}AlMe and 3 form four-coordinate complexes with slightly distorted tetrahedral geometries, whereas the geometry in the Lewis acidic five-coordinate (S)-{?O}GaCl·THF is a distorted trigonal bipyramid. These alkyl complexes do not react cleanly, if at all, with protic sources. The indium(III) compound 6, which is for instance inert towards iPrOH or BnOH even after hours at 70°C, catalyses at 95°C the controlled, immortal ring-opening polymerisation of racemic lactide (up to 1000 equivalents) in the presence of excess BnOH as a chain transfer agent. It affords atactic, monodisperse polylactides with predictable molecular weights.
