23356-96-9Relevant articles and documents
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Gassman,Fentiman
, p. 2388,2390 (1967)
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Asymmetric Synthesis. Metal Complex Mediated Synthesis of Chiral Glycine by Enantioselective Proton Exchange
Dokuzovic, Zdravko,Roberts, Nicholas K.,Sawyer, Jeffery F.,Whelan, John,Bosnich, B.
, p. 2034 - 2039 (1986)
The complex (1+), a species containing a chiral tridentate triamine ligand, (S,S)-proam, and a tridentate ligand incorporating a glycine residue, picgly, has been prepared.The α-protons of the coordinated glycine residue exchange at different rates in basic D2O solutions.The difference in rate was found to be 7.8:1 in favor of the pro-S proton at pD 11.2 at 25 deg C with a NaHCO3/Na2CO3 buffer.It is proposed that the origins of this enantiosection arise from both steric and hydrogen-bonding effects as inferred from the determined crystal structure of the complex.A kinetic analysis of the exchange process shows that the system is essentially that of an asymmetric synthesis (CH2 -> CHD) followed by a reinforced kinetic resolution (CHD -> CD2).As such, the optical purity of the chiral glycine (NH2CHDCO2H) continuously increases with the extent of reaction.This was confirmed.It is suggested that the present kinetic relationships are representative of the majority of asymmetric syntheses involving enantiotopic atoms or groups, and it follows that, for such systems, quoting an enantiomeric excess has meaning only when the extent of reaction is specified.
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.
Understanding the Alkylation Mechanism of 3-Chloropiperidines – NMR Kinetic Studies and Isolation of Bicyclic Aziridinium Ions
Helbing, Tim,Georg, Mats,St?hr, Fabian,Carraro, Caterina,Becker, Jonathan,Gatto, Barbara,G?ttlich, Richard
, p. 5905 - 5913 (2021/10/29)
The present study describes the kinetic analysis of the 3-chloropiperidine alkylation mechanism. These nitrogen mustard-based compounds are expected to react via a highly electrophilic bicyclic aziridinium ion, which is readily attacked by nucleophiles. Halide abstraction using silver salts with weakly coordinating anions lead to the isolation of these proposed intermediates, whereas their structure was confirmed by single crystal XRD. Kinetic studies of the aziridinium ions also revealed notable reactivity differences of the C5 gem-methylated compounds and their unmethylated counterparts. The observed reactivity trends were also reflected by NMR studies in aqueous solution and DNA alkylation experiments of the related 3-chloropiperidines. Therefore, the underlying Thorpe-Ingold effect might be considered as another option to adjust the alkylation activity of these compounds.
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.