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Soai's asymmetric autocatalysis represents a highly remarkable example for spontaneous symmetry breaking and enantioselective amplification in the enantioselective alkylation of pyrimidine-5-carbaldehydes to the corresponding chiral pyrimidine alcohols. Recently, zinc hemiacetalate complexes, formed from pyrimidine-5-carbaldehydes and the chiral product alcohol, were identified by in situ high-resolution mass spectrometric measurements as highly active transient asymmetric catalysts in this autocatalytic transformation. To study the formation of such hemiacetals and their stereodynamic properties, we focused on the synthesis of coumarin homolog biaryl systems with carbaldehyde and alcohol substituents. Such systems are able to form hemiacetals by intramolecular cyclization. An interesting feature of the substituted biaryl backbone is that tropos and atropos systems can be obtained, enabling or disabling the intramolecular cyclization to hemiacetals. Biaryl structures with various functional groups were synthesized, and the equilibrium and stereodynamics between the closed and open structures were investigated by dynamic enantioselective HPLC (DHPLC). The enantiomerization barriers ΔG ǂ and activation parameters ΔH ǂ and ΔS ǂ were determined from temperature dependent kinetic measurements., (© 2023 The Authors. Chirality published by Wiley Periodicals LLC.)

Chiral compounds are ubiquitous in nature and play a pivotal role in biochemical processes, in chiroptical materials and applications, and as chiral drugs. The analysis and determination of the enantiomeric ratio (er) of chiral compounds is of enormous scientific, industrial, and economic importance. Chiral separation techniques and methods have become indispensable tools to separate chiral compounds into their enantiomers on an analytical as well on a preparative level to obtain enantiopure compounds. Chiral gas chromatography and high-performance liquid chromatography have paved the way and fostered several research areas, that is, asymmetric synthesis and catalysis in organic, medicinal, pharmaceutical, and supramolecular chemistry. The development of highly enantioselective chiral stationary phases was essential. In particular, the elucidation and understanding of the underlying enantioselective supramolecular separation mechanisms led to the design of new chiral stationary phases. This review article focuses on the development of chiral stationary phases for gas chromatography. The fundamental mechanisms of the recognition and separation of enantiomers and the selectors and chiral stationary phases used in chiral gas chromatography are presented. An overview over syntheses and applications of these chiral stationary phases is presented as a practical guidance for enantioselective separation of chiral compound classes and substances by gas chromatography., (© 2022 The Authors. Chirality published by Wiley Periodicals LLC.)

Chiral compounds with a 1,2-diamine structure motif and their derivatives are of great interest in organic chemistry and are broadly used in asymmetric transformations, as chiral auxiliaries, (co)ligands, and ligand core structure. Here, we present a straightforward, diastereoselective synthesis for a diamide-bridged biaryl ligand. The ring closing reaction of the racemic atropos biphenyl 6,6'-dimethoxy-[1,1'-biphenyl]-2,2'-dicarboxylic acid with (R,R)-diaminocyclohexane yields the diasteromerically and enantiomerically pure cyclic (S ax ,R,R)-BIPOL, which can be used as a versatile chiral ligand. By NMR spectroscopy, we observed the formation of intermolecular aggregates of the diamide-bridged BIPOL with anhydrous DMSO-d 6 . DFT calculations at the B3LYP/6-31G* level of theory corroborate the high interconversion barrier for the biaryl axis of ΔG ǂ  = 148.7 kJ mol -1 and the favoured formation of (S ax ,R,R)-BIPOL as single stereoisomer., (© 2022 The Authors. Chirality published by Wiley Periodicals LLC.)

Chirality plays a pivotal role in an uncountable number of biological processes, and nature has developed intriguing mechanisms to maintain this state of enantiopurity. The strive for a deeper understanding of the different elements that constitute such self-sustaining systems on a molecular level has sparked great interest in the studies of autoinductive and amplifying enantioselective reactions. The design of these reactions remains highly challenging; however, the development of generally applicable principles promises to have a considerable impact on research of catalyst design and other adjacent fields in the future. Here, we report the realization of an autoinductive, enantioselective self-inhibiting hydrogenation reaction. Development of a stereodynamic catalyst with chiral sensing abilities allowed for a chiral reaction product to interact with the catalyst and change its selectivity in order to suppress its formation, which caused a reversal of selectivity over time., (© 2019 The Authors. Chirality published by Wiley Periodicals, Inc.)

We present rhodium catalysts that contain stereodynamic axially chiral biphenol-derived phosphinite ligands modified with non-stereoselective amides for non-covalent interactions. A chirality transfer was achieved with (R)- or (S)-acetylphenylalanine methyl amide, and the interaction mechanism was investigated by NMR measurements. These interactions at the non-stereoselective interaction sites and the formation of supramolecular complexes result in an enrichment of either the (R ax )- or (S ax ) enantiomer of the tropos catalysts, which in turn provide the (R)- or (S)-acetylphenylalanine methyl ester in the hydrogenation of (Z)-methyl-α-acetamidocinnamate., (© 2018 Wiley Periodicals, Inc.)

Stereodynamic ligands and complexes bearing functional groups to attach chiral or achiral binding sites and auxiliaries are highly attractive due to the interesting opportunities for controlling the stereochemical outcome of enantioselective transformations. In this study we report the preparation of a 3,3'-functionalized biphenol (BIPOL) phosphoramidite ligand (P Am ) bearing 3,5-dichlorobenzoyl (3,5-DCB) amide binding sites for noncovalent interactions. Upon coordination to [Rh(COD) 2 ]BF 4 this substitution pattern directs one of the 3,5-DCB binding sites in close proximity of the metal center resulting in liberation of both COD ligands and the formation of a [Rh(P Am ) 2 ]BF 4 complex. Coordination of the amide carbonyl unit was found to be reversible, since the complex acted as an active catalyst in the hydrogenation of dehydroamino acid derivatives. X-ray crystallographic investigation revealed that the second 3,5-DCB unit is capable of forming noncovalent π-π interactions connecting both phosphoramidite ligands., (© 2016 Wiley Periodicals, Inc.)

Enantiomerization of allylic trifluoromethyl sulfoxides occurs spontaneously at room temperature through the corresponding allylic trifluoromethanesulfenates via a [2,3]-sigmatropic rearrangement. Dynamic enantioselective high-performance liquid chromatography (HPLC) analysis revealed the stereodynamics of these sulfoxides ranging from chromatographic resolution to peak coalescence at temperatures between 5 and 53 °C. The rate constant of enantiomerization and activation parameters were determined and compared with Density Functional Theory (DFT) calculations., (© 2015 Wiley Periodicals, Inc.)

trans-1,2-Disubstituted diaziridines form stable enantiomers at ambient conditions because of the two stereogenic pyramidal nitrogen atoms. Functionalized trans-1,2-disubstituted diaziridines can be utilized as a chiral switching moiety between two enantiomeric states in more complex molecular structures. However, the synthesis of functionalized diaziridines is quite challenging, because of the limited tolerance of reaction conditions that can be applied. Here we present a strategy to make trans-1,2-disubstituted diaziridines accessible as versatile building blocks in C-C-bond formations, i.e., the Heck reaction, and therefore introducing aryl substituents. The synthesis of trans-1,2-dialkenyl diaziridines with terminal alkenyl substituents and their stereodynamic properties are described., (© 2014 Wiley Periodicals, Inc.)

On-column reaction gas chromatography combines the power of separation and rapid analysis of reactants and reaction products with screening of reactions in a single step. Not only conversions but the reaction rates at various temperatures can be obtained from single measurements, making this approach superior to the time-consuming measurements typically performed in reaction progress analysis. However, this approach has only been used in the investigation of interconversion processes, rearrangement reactions, and only a few examples of higher-order reactions are known. Here we present the screening of immobilized gadolinium(III)-tris[(1R,4S)-3-heptafluorobutanoyl-camphor] in the Danishefsky-hetero-Diels-Alder-reaction by enantioselective on-column reaction gas chromatography utilizing cryogenic focusing to achieve catalytic conversions in this higher-order reaction and subsequent separation of the enantiomeric product mixture to determine the enantiomeric ratio. The results obtained by this approach could be transferred to the conventional batch reaction at a larger scale, demonstrating that on-column reaction chromatography provides reliable results in the screening of enantioselective reactions., (Copyright © 2014 Wiley Periodicals, Inc.)

Diaziridines are very interesting representatives of organic compounds containing stereogenic nitrogen atoms. In particular, 1,2-dialkyldiaziridines show extraordinarily high stereointegrity. The lone electron pairs of the nitrogen atoms are in trans configuration, avoiding a four-electron repulsive interaction. Furthermore, the trans configuration of the substituents at the nitrogen atoms is energetically favored because of reduced steric interactions. Therefore only two stereoisomers (enantiomers) are observed. At elevated temperatures the enantiomers are interconverting because of the limited stereointegrity of the chirotopic nitrogen atoms. The enantiomerization rate constants and the activation parameters of interconversion are of great interest. Here, we investigated the stereodynamics of a set of small 1,2-dialkyldiaziridines bearing short substituents (Me, Et, iPr, tBu), using enantioselective dynamic gas chromatography (DGC). Separation of enantiomers of all compounds, including the highly volatile 1,2-dimethyldiaziridine, was achieved using heptakis(2,3-di-O-ethyl-6-O-tert-butyldimethylsilyl)-β-cyclodextrin in 50% PS086 (w/w) as chiral stationary phase in fused silica capillaries with a length of up to 50 m. Measurements at variable temperatures were performed and reaction rate constants were determined using the unified equation of chromatography implemented in the software DCXplorer. The activation barriers at room temperature for 1-(tert-butyl)-2-ethyldiaziridine, ΔG(╪)(298K) = 123.8 kJ mol(-1) (ΔH(╪) = 115.5±2.9 kJ mol(-1), ΔS(╪) = -28±1 J mol(-1) K(-1)), and 1-ethyl-2-isopropyldiaziridine, ΔG(╪)(298K) = 124.2 kJ mol(-1) (ΔH(╪) = 113.1±2.4 kJ mol(-1), ΔS(╪) = -37±2 J mol(-1) K(-1)), were determined, representing some of the highest values observed for nitrogen inversion in diaziridines., (Copyright © 2013 Wiley Periodicals, Inc.)

We investigated the stereodynamics of 5,5'-substituted tropos BIPHEP ligands (2,2'-bis(diphenylphosphino)-biphenyls) by enantioselective dynamic high-performance liquid chromatography (DHPLC) to elucidate the influence of the substitution pattern and electronics of the substituents (methyl, methoxy, and hydroxyl groups). By temperature-dependent dynamic HPLC measurements the activation parameters ΔG(╪), ΔH(╪), and ΔS(╪) could be determined with high precision, revealing that the activation barrier of these 5,5'-substituted BIPHEP ligands ranges in a narrow band between 87.8 and 93.0 kJ mol(-1), making them highly attractive as deracemizable dynamic chiral ligands in asymmetric catalysis. Interestingly, the activation parameters are highly influenced by a hydroxyl or methoxy group in the 5,5'-position of the BIPHEP ligands., (Copyright © 2012 Wiley Periodicals, Inc.)

The antidepressant drug tetramezine [1,2-bis-(3,3-dimethyldiaziridin-1-yl)ethane] consists of two bridged diaziridine moieties with four stereogenic nitrogen centers, which are stereolabile and, therefore, are prone to interconversion. The adjacent substituents at the nitrogen atoms of the diaziridines moieties exist only in an antiperiplanar conformation, which results in a coupled interconversion. Therefore, three stereoisomers exist (meso form and two enantiomeric forms), which epimerize when the diaziridine moieties are regarded as stereogenic units due to the coupled interconversion. Here, we have investigated the epimerization between the meso and enantiomeric forms by dynamic gas chromatography. Temperature-dependent measurements were performed, and reaction rate constants were determined using the unified equation of chromatography implemented in the software DCXplorer. The activation barriers of the epimerization were found to be ΔG(≠) = 100.7 kJ mol(-1) at 25°C and ΔG(≠) = 104.5 kJ mol(-1) at 37°C, respectively. The activation enthalpy and entropy were determined to be ΔH(≠) = 70.3 ± 0.4 kJ mol(-1) and ΔS(≠) = -102 ± 2 J mol(-1) K(-1) ., (Copyright © 2010 Wiley-Liss, Inc.)

N-alkylated trans-diaziridines are an intriguing class of compounds with two stereogenic nitrogen atoms which easily interconvert. In the course of our investigations of the nature of the interconversion process via nitrogen inversion or electrocyclic ring opening ring closure, we synthesized and characterized the three constitutionally isomeric diaziridines 1,2-di-n-propyldiaziridine 1, 1-isopropyl-2-n-propyldiaziridine 2, and 1,2-diisopropyldiaziridine 3 to study the influence of the substituents on the interconversion barriers. Enantiomer separation was achieved by enantioselective gas chromatography on the chiral stationary phase Chirasil-beta-Dex with high separation factors alpha (1-isopropyl-2-n-propyldiaziridine: 1.18; 1, 2-diisopropyldiaziridine: 1.24; 100 degrees C 50 kPa He) for the isopropyl substituted diaziridines. These compounds showed pronounced plateau formation between 100 and 150 degrees C, and peak coalescence at elevated temperatures. The enantiomerization barriers DeltaG(double dagger) and activation parameters DeltaH(double dagger) and DeltaS(double dagger) were determined by enantioselective dynamic gas chromatography (DGC) and direct evaluation of the elution profiles using the unified equation implemented in the software DCXplorer. Interestingly, 1-isopropyl-2-n-propyldiaziridine and 1,2-diisopropyldiaziridine exhibit similar high interconversion barriers DeltaG(double dagger) (100 degrees C) of 128.3 +/- 0.4 kJ mol(-1) and 129.8 +/- 0.4 kJ mol(-1), respectively, which indicates that two sterically demanding substituents do not substantially increase the barrier as expected for a distinct nitrogen inversion process., (2009 Wiley-Liss, Inc.)

Electrokinetic chromatography was employed to separate the enantiomers of two novel functionalized ruthenium(II) complexes with different polypyridyl coordination spheres. The use of anionic carboxymethyl-beta-cyclodextrin as chiral mobile phase additive resulted in maximum efficiency and resolution for the enantiomer separation of both transition metal complexes. The syntheses of the [4-(3-hydroxypropyl)-4'-methyl-2,2'-bipyridine]-bis(2,2'-bipyridine)rethenium(II)-bis(tetrafluoroborate) and [4-(3-hydroxypropyl)-4'-methyl-2,2'-bipyridine]-bis(4,4'-dimethyl-2,2'-bypyridine)ruthenium(II)-bis(tetrafluoroborate) complexes and their complete characterization by means of two-dimensional (1)H and (13)C[(1)H] NMR techniques ((1)H-(1)H COSY and (1)H-(13)C HMQC) as well as elemental analyses and MALDI-TOFMS are described in detail. The functionalized complexes can be used as building blocks for further reactions with polymers, biopolymers, surfaces and nanoparticles., (Copyright Wiley-Liss, Inc.)

The axially chiral allenes dimethyl-1,3-allenedicarboxylate 1 and diethyl-1,3-allenedicarboxylate 2 show characteristic plateau formation during enantioselective GC separation on the chiral stationary liquid phase Chirasil-beta-Dex. The elution profiles, obtained from temperature-dependent dynamic GC (DGC) experiments (1: 100-140 degrees C; 2: 110-150 degrees C) were evaluated with the recently derived approximation function (AF) k1(approx) = f(t(R)(A),t(R)(B),w(h)(A),h(plateau), N) to yield the enantiomerization rate constant directly k(1). These values were compared with those obtained by computer-aided simulation with ChromWin. The Eyring activation parameters of the experimental interconversion profiles were determined to be: DeltaG(#)(298.15 K) = 103.6 +/- 0.9 kJ mol(-1), DeltaH(#) = 44.7 +/- 0.4 kJ mol(-1), DeltaS(#) = -198 +/- 7 J K(1) mol(-1) for dimethyl-1,3-allenedicarboxylate 1, and DeltaG(#)(298.15 K) = 103.5 +/- 1.1 kJ mol(-1), DeltaH(#) = 44.7 +/- 0.5 kJ mol(-1), DeltaS(#) = -197 +/- 9 J K(-1) mol(-1) for diethyl-1,3-allenedicarboxylate 2. The approximation function (AF) presented here allows the fast determination of rate constants k(1) and activation barriers of enantiomerization DeltaG(#) from chromatographic parameters without extensive computer simulation., (Copyright 2002 Wiley-Liss, Inc.)

In recent years, dynamic chromatography and stopped-flow chromatographic techniques have become versatile tools for the determination of enantiomerization and isomerization barriers. Increasing demands for the stereochemical safety of chiral drugs contributed to the rapid development of new techniques. New computer-aided evaluation systems allow the on-line determination of interconversion barriers from the experimental chromatograms. Both dynamic chromatography and stopped-flow chromatography have been applied to the entire range of chromatographic methods (GC, SFC, HPLC, CE)., (Copyright 2001 Wiley-Liss, Inc.)