- Asymmetric hydroalkylation of alkynes and allenes with imidazolidinone derivatives: α-alkenylation of α-amino acids
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This work reports a new method for the synthesis of quaternary α-alkenyl substituted amino acids by the enantio- and diastereoselective addition of imidazolidinone derivatives to alkynes and allenes. Further hydrolysis of the imidazolidinone products under acidic conditions afforded biologically relevant amino acid derivatives. This method is geometry-selective (E-isomer), enantio- and diastereoselective, and products were obtained in good to excellent yields. The utility of this new methodology is proved by its operational simplicity and the successful accomplishment of gram-scale reactions. Experimental and computational studies suggest the key role of Li in terms of selectivity and support the proposed reaction mechanism.
- Bauer, Felix,Breit, Bernhard,Khosravi, Hormoz,Panahi, Farhad
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Read Online
- Basicities and Nucleophilicities of Pyrrolidines and Imidazolidinones Used as Organocatalysts
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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.
- An, Feng,Maji, Biplab,Min, Elizabeth,Ofial, Armin R.,Mayr, Herbert
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supporting information
p. 1526 - 1547
(2020/02/04)
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- UNNATURAL AMINO ACIDS
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The present invention relates to a process for the preparation compounds of Formula (I): Formula (I) wherein X, Z, Q, Ar, R1, R2, R3 and R4 are each as defined herein. The present invention also relates to processes for the preparation of the compounds of quaternary amino acids and hydantions, to compound of Formula(I), to intermediate compounds of Formula (II), to quaternary amino acid compounds of Formula (III) and to hydantoin compounds of Formula (IV).
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Paragraph 00185; 00211
(2018/07/05)
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- Enantioselective oxidation of thioanisole to metyl phenyl sulfoxide by chiral compounds bearing N-Cl bond
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Chiral sulfoxides are used in asymmetric synthesis and are present in various biologically active compounds. Asymmetric synthesis of the sulfoxides has been performed by chiral metal complexes and non-metals containing peroxide and oxide moieties. In this study, a new metal free method has been developed to oxidize thioanisole into methyl phenyl sulfoxide with easily accessible chiral compounds carrying N-Cl bond. For this purpose, chiral amine and amide bearing reagents were synthesized and chlorinated by using N-chlorosuccinimide. In oxidation reactions, chiral information has been transferred from N-chloramines to sulfides. With chlorinated chiral reagents, we observed enantioenriched sulfoxide formation. Although the observed results are promising, the best chiral amines are yet to be found. This is the first report on such a reaction, to the best of our knowledge.
- Ipek, Halil,Akdag, Akin
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p. 1285 - 1293
(2015/08/18)
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- Aromatic Interactions in Organocatalyst Design: Augmenting Selectivity Reversal in Iminium Ion Activation
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Substituting N-methylpyrrole for N-methyindole in secondary-amine-catalysed Friedel-Crafts reactions leads to a curious erosion of enantioselectivity. In extreme cases, this substrate dependence can lead to an inversion in the sense of enantioinduction. Indeed, these closely similar transformations require two structurally distinct catalysts to obtain comparable selectivities. Herein a focussed molecular editing study is disclosed to illuminate the structural features responsible for this disparity, and thus identify lead catalyst structures to further exploit this selectivity reversal. Key to effective catalyst re-engineering was delineating the non-covalent interactions that manifest themselves in conformation. Herein we disclose preliminary validation that intermolecular aromatic (CH-π and cation-π) interactions between the incipient iminium cation and the indole ring system is key to rationalising selectivity reversal. This is absent in the N-methylpyrrole alkylation, thus forming the basis of two competing enantio-induction pathways. A simple L-valine catalyst has been developed that significantly augments this interaction.
- Holland, Mareike C.,Metternich, Jan Benedikt,Daniliuc, Constantin,Schweizer, W. Bernd,Gilmour, Ryan
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p. 10031 - 10038
(2015/07/07)
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- Preparation and structures of 2-substituted 5-benzyl-3-methylimidazolidin- 4-one-derived iminium salts, reactive intermediates in organocatalytic transformations involving α,β-unsaturated aldehydes
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Preparations of the title compounds, 5-7 (Scheme 1 and Table 1), of their ammonium salts, 9-11 (Scheme 2 and Table 2), and of the corresponding cinnamaldehyde-derived iminium salts 12-14 (Scheme 3 and Table 3) are reported. The X-ray crystal structures of 15 cinnamyliminium PF6 salts have been determined (Table 4). Selected 1H-NMR data (Table 5) of the ammonium and iminium salts are discussed, and structures in solution are compared with those in the solid state. Copyright
- Gro?elj, Uro?,Beck, Albert,Schweizer, W. Bernd,Seebach, Dieter
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p. 751 - 796
(2014/07/07)
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- Highly enantioselective access to cannabinoid-type tricyles by organocatalytic Diels-Alder reactions
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After prosperous domino reactions towards benzopyrans, the products were used as the starting material in Lewis acid catalyzed and organocatalytic Diels-Alder reactions to build up a tricyclic system. Herein, an asymmetric induction up to 96% enantiomeric excess was obtained by the use of imidazolidinone catalysts. This approach can be utilized to construct the tricyclic system in numerous natural products, in particular the scaffold of tetrahydrocannabinol (THC) being the most representative one. Compared with other published methods, condensation with a preexisting cyclohexane moiety in the precursor is needed to gain the heterogenic tricycle systems, whereas we present a novel strategy towards cannabinoid derivatives based on a flexible modular synthesis.
- Braese, Stefan,Volz, Nicole,Glaeser, Franziska,Nieger, Martin
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supporting information
p. 1385 - 1392
(2012/11/07)
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- Preparation of the MacMillan imidazolidinones
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A general method for the preparation of the MacMillan imidazolidinones is described. Treatment of an α-amino amide with a carbonyl compound in refluxing chloroform in the presence of Yb(OTf)3 (1 mol %) provides convenient access to the corresponding imidazolidinones.
- Samulis, Leopold,Tomkinson, Nicholas C.O.
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p. 4263 - 4267
(2011/06/26)
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- Enantioselective transformation of alpha,beta-unsaturated ketones using chiral organic catalysts
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Nonmetallic organic catalysts are provided that facilitate the enantioselective reaction of α,β-unsaturated ketones. The catalysts are chiral imidazolidinone compounds having the structure of formula (IIA) or (IIB) or are acid addition salts thereof, wherein, in one preferred embodiment, R1 is C1-C6 alkyl, R2is phenyl or 2-methylfuryl, R3 and R4 are hydrogen, and R5 is phenyl optionally substituted with 1 or 2 substituents selected from the group consisting of halo, hydroxyl, and C1-C6 alkyl The chiral imidazolidinones are useful in catalyzing a wide variety of reactions, including cycloaddition reactions, Friedel-Crafts alkylation reactions, and Michael additions.
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Page/Page column 10
(2008/06/13)
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- The enantioselective organocatalytic 1,4-addition of electron-rich benzenes to α,β-unsaturated aldehydes
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The first enantioselective organocatalytic alkylation of electron-rich benzene rings with α,β-unsaturated aldehydes has been accomplished. The use of iminium catalysis has provided a new strategy for the enantioselective construction of benzylic stereogenicity, an important chiral synthon for natural product and medicinal agent synthesis. The (2S,5S)-5-benzyl-2-tert-butylimidazolidinone amine catalyst has been found to mediate the conjugate addition of a wide variety of substituted and unsubstituted anilines to unsaturated aldehydes. A diverse spectrum of aldehyde substrates can also be accommodated in this new organocatalytic transformation. While catalyst quantities of 10 mol % were generally employed in this study, successful alkylations conducted with catalyst loadings as low as 1 mol % are described. Copyright
- Paras, Nick A.,MacMillan, David W. C.
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p. 7894 - 7895
(2007/10/03)
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- Herstellung enantiomerenreiner cis- oder trans-konfigurierter 2-(tert-Butyl)-3-methylimidazolidin-4-one aus den Aminosaeuren (S)-Alanin, (S)-Phenylalanin, (R)-Phenylglycin, (S)-Methionin und (S)-Valin.
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In contrast to α-hydroxy and α-mercapto carboxylic acids, simple α-amino acids do not form acetal-type derivatives (2, X=NH) with pivalaldehyde.For the generation of amino-acid-derived chiral, nonracemic enolates (cf.3), and hence, for the α-alkylation of amino acids without racemization and without an external chiral auxiliary, the imidazolidinones 12-14 were prepared diastereoselectively.To this end, the methyl or ethyl esters of amino-acid hydrochlorides were first converted to N-methylamides of amino acids which in turn were condensed with pivalaldehyde to give (neopentylidenamino)amides (11).These Schiff bases could be cyclized either to trans- or to cis-imidazolidinones (12, 14 and 13, respectively), which were obtained in enantiomerically pure form after recrystallization.The enantiomeric purities were confirmed by HPLC with chiral stationary phases or by 1H-NMR spectroscopy in the presence of chiral shift reagents.The configurations (cis, trans) were assigned by NOE measurements on 300- or 360-MHz 1H-NMR spectrometers.
- Naef, Reto,Seebach, Dieter
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p. 135 - 143
(2007/10/02)
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