E-Mail Alert

Add your e-mail address to receive forthcoming issues of this journal:

Journal Browser

Journal Browser

Special Issue "Dynamic Stereochemistry"

Quicklinks

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Theoretical Chemistry".

Deadline for manuscript submissions: closed (30 November 2014)

Special Issue Editor

Guest Editor
Prof. Dr. Stig Allenmark

Department of Chemistry and Molecular Biology, Goteborg University, SE-41296 Goteborg, Sweden
Website | E-Mail
Phone: +46 31 932315
Fax: +46 317723840
Interests: enantioselectivity in chromatography and in catalytic reactions; chiroptical methods for solving stereochemical problems

Special Issue Information

Dear Colleagues,

The Nobel Prize in Chemistry 1969 was awarded jointly to Derek H. R. Barton and Odd Hassel "for their contributions to the development of the concept of conformation and its application in chemistry". Their work, which started already in the 1930’s, can be said to mark the transition from constitutional to conformational aspects of organic molecules and thereby paved the way to studies of dynamic stereochemistry. The later development of this field has been enormous and of immense importance for our understanding of a variety of phenomena, like rotation and inversion barriers or mechanisms of enantiomer interconversions in stereochemically labile compounds as well as other stereoselective interconversions of compounds exhibiting different types of chirality.
This Special Issue on Dynamic Stereochemistry is intended to attract researchers in this field who want to contribute their latest results to the forum of Molecules. It is my hope that a good deal of interesting papers will be submitted that will reflect the potential and rapid development in this important area of organic chemistry.

Dr. Stig Allenmark
Guest Editor

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed Open Access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs).


Keywords

  • conformational analysis
  • intramolecular dynamics
  • barriers to rotation
  • inversion barriers
  • hypervalent compounds
  • pseudorotation
  • foldamers
  • molecular propellers
  • dynamic kinetic resolution
  • NMR-studies
  • dynamic chromatography
  • potential energy surfaces (PES)
  • computational methods

Published Papers (13 papers)

View options order results:
result details:
Displaying articles 1-13
Export citation of selected articles as:

Research

Jump to: Review

Open AccessArticle Acid Catalyzed Alcoholysis of Sulfinamides: Unusual Stereochemistry, Kinetics and a Question of Mechanism Involving Sulfurane Intermediates and Their Pseudorotation
Molecules 2015, 20(2), 2949-2972; doi:10.3390/molecules20022949
Received: 19 December 2014 / Accepted: 3 February 2015 / Published: 11 February 2015
Cited by 2 | PDF Full-text (1169 KB) | HTML Full-text | XML Full-text
Abstract
The synthesis of optically active sulfinic acid esters has been accomplished by the acid catalyzed alcoholysis of optically active sulfinamides. Sulfinates are formed in this reaction with a full or predominant inversion of configuration at chiral sulfur or with predominant retention of configuration.
[...] Read more.
The synthesis of optically active sulfinic acid esters has been accomplished by the acid catalyzed alcoholysis of optically active sulfinamides. Sulfinates are formed in this reaction with a full or predominant inversion of configuration at chiral sulfur or with predominant retention of configuration. The steric course of the reaction depends mainly on the size of the dialkylamido group in the sulfinamides and of the alcohols used as nucleophilic reagents. It has been found that bulky reaction components preferentially form sulfinates with retention of configuration. It has been demonstrated that the stereochemical outcome of the reaction can be changed from inversion to retention and vice versa by adding inorganic salts to the acidic reaction medium. The unusual stereochemistry of this typical bimolecular nucleophilic substitution reaction, as confirmed by kinetic measurements, has been rationalized in terms of the addition-elimination mechanism, A-E, involving sulfuranes as intermediates which undergo pseudorotations. Full article
(This article belongs to the Special Issue Dynamic Stereochemistry)
Figures

Open AccessArticle Comparison of the Separation Performances of Cinchona Alkaloid-Based Zwitterionic Stationary Phases in the Enantioseparation of β2- and β3-Amino Acids
Molecules 2015, 20(1), 70-87; doi:10.3390/molecules20010070
Received: 10 November 2014 / Accepted: 15 December 2014 / Published: 23 December 2014
Cited by 7 | PDF Full-text (874 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The enantiomers of twelve unusual β2- and β3-homoamino acids containing the same side-chains were separated on chiral stationary phases containing a quinine- or quinidine-based zwitterionic ion-exchanger as chiral selector. The effects of the mobile phase composition, the nature and
[...] Read more.
The enantiomers of twelve unusual β2- and β3-homoamino acids containing the same side-chains were separated on chiral stationary phases containing a quinine- or quinidine-based zwitterionic ion-exchanger as chiral selector. The effects of the mobile phase composition, the nature and concentration of the acid and base additives and temperature on the separations were investigated. The changes in standard enthalpy, ∆(∆H°), entropy, ∆(∆S°), and free energy, ∆(∆G°), were calculated from the linear van’t Hoff plots derived from the ln α vs. 1/T curves in the studied temperature range (10–50 °C). The values of the thermodynamic parameters depended on the nature of the selectors, the structures of the analytes, and the positions of the substituents on the analytes. A comparison of the zwitterionic stationary phases revealed that the quinidine-based ZWIX(−)™ column exhibited much better selectivity for both β2- and β3-amino acids than the quinine-based ZWIX(+)™ column, and the separation performances of both the ZWIX(+)™ and ZWIX(−)™ columns were better for β2-amino acids. The elution sequence was determined in some cases and was observed to be R < S and S < R on the ZWIX(+)™ and ZWIX(−)™ columns, respectively. Full article
(This article belongs to the Special Issue Dynamic Stereochemistry)
Open AccessArticle Liquid Chromatographic Resolution of Fendiline and Its Analogues on a Chiral Stationary Phase Based on (+)-(18-Crown-6)-2,3,11,12-tetracarboxylic Acid
Molecules 2014, 19(12), 21386-21397; doi:10.3390/molecules191221386
Received: 4 November 2014 / Revised: 5 December 2014 / Accepted: 11 December 2014 / Published: 19 December 2014
Cited by 4 | PDF Full-text (782 KB) | HTML Full-text | XML Full-text
Abstract
Fendiline, an effective anti-anginal drug for the treatment of coronary heart diseases, and its sixteen analogues were resolved on a CSP based on (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid. Fendiline was resolved quite well with the separation factor (α) of 1.25 and resolution (RS) of
[...] Read more.
Fendiline, an effective anti-anginal drug for the treatment of coronary heart diseases, and its sixteen analogues were resolved on a CSP based on (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid. Fendiline was resolved quite well with the separation factor (α) of 1.25 and resolution (RS) of 1.55 when a mobile phase consisting of methanol–acetonitrile–trifluoroacetic acid–triethylamine at a ratio of 80/20/0.1/0.5 (v/v/v/v) was used. The comparison of the chromatographic behaviors for the resolution of fendiline and its analogues indicated that the 3,3-diphenylpropyl group bonded to the secondary amino group of fendiline is important in the chiral recognition and the difference in the steric bulkiness between the phenyl group and the methyl group at the chiral center of fendiline is also important in the chiral recognition. Full article
(This article belongs to the Special Issue Dynamic Stereochemistry)
Open AccessArticle Homoconjugation vs. Exciton Coupling in Chiral α,β-Unsaturated Bicyclo[3.3.1]nonane Dinitrile and Carboxylic Acids
Molecules 2014, 19(7), 9893-9906; doi:10.3390/molecules19079893
Received: 4 May 2014 / Revised: 3 June 2014 / Accepted: 5 June 2014 / Published: 8 July 2014
PDF Full-text (606 KB) | HTML Full-text | XML Full-text
Abstract
The chiroptical properties of enantiomerically pure bicyclo[3.3.1]nona-2,6-diene-2,6-dicarbonitrile and related acids were studied by circular dichroism spectroscopy and theoretical computations. A consideration of the molecular structure of the synthesized difunctional compounds revealed that chromophores are predisposed to transannular through-space interaction due to a favourable
[...] Read more.
The chiroptical properties of enantiomerically pure bicyclo[3.3.1]nona-2,6-diene-2,6-dicarbonitrile and related acids were studied by circular dichroism spectroscopy and theoretical computations. A consideration of the molecular structure of the synthesized difunctional compounds revealed that chromophores are predisposed to transannular through-space interaction due to a favourable conformation of the bicyclic skeleton and a rather small interchromophoric distance. Evidence for non-exciton-type coupling between the two acrylonitrile and acrylate moieties in 3 and 4, respectively, was obtained by chiroptical spectroscopy and DFT calculations. Full article
(This article belongs to the Special Issue Dynamic Stereochemistry)
Open AccessArticle Ni-Catalyzed Homoallylation of Polyhydroxy N,O-Acetals with Conjugated Dienes Promoted by Triethylborane
Molecules 2014, 19(7), 9288-9306; doi:10.3390/molecules19079288
Received: 4 April 2014 / Revised: 13 June 2014 / Accepted: 23 June 2014 / Published: 2 July 2014
PDF Full-text (299 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In the presence of Ni-catalyst and triethylborane, N,O-acetals prepared from glycolaldehyde and glyceraldehyde with primary amines in situ underwent homoallylation with conjugated dienes to provide 2-amino-5-hexenols in high regio- and stereoselectivity. Under similar reaction conditions, N,O-acetals from
[...] Read more.
In the presence of Ni-catalyst and triethylborane, N,O-acetals prepared from glycolaldehyde and glyceraldehyde with primary amines in situ underwent homoallylation with conjugated dienes to provide 2-amino-5-hexenols in high regio- and stereoselectivity. Under similar reaction conditions, N,O-acetals from carbohydrates with primary amines provided the corresponding polyhydroxy-bishomoallylamines in good to reasonable yields. Full article
(This article belongs to the Special Issue Dynamic Stereochemistry)
Open AccessArticle Chiroptical Properties and the Racemization of Pyrene and Tetrathiafulvalene-Substituted Allene: Substitution and Solvent Effects on Racemization in Tetrathiafulvalenylallene
Molecules 2014, 19(3), 2829-2841; doi:10.3390/molecules19032829
Received: 21 January 2014 / Revised: 21 February 2014 / Accepted: 23 February 2014 / Published: 4 March 2014
Cited by 4 | PDF Full-text (818 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Dissymmetric 1,3-diphenylallene derivative 3 connected with 4,5-bis(methyl-thio)tetrathiafulvalenyl and 1-pyrenyl substituents was prepared and characterized. The molecular structure was determined by X-ray crystallographic analysis. Optical resolution was accomplished using a recycling chiral HPLC, and its chiroptical properties were examined with optical rotation and electronic
[...] Read more.
Dissymmetric 1,3-diphenylallene derivative 3 connected with 4,5-bis(methyl-thio)tetrathiafulvalenyl and 1-pyrenyl substituents was prepared and characterized. The molecular structure was determined by X-ray crystallographic analysis. Optical resolution was accomplished using a recycling chiral HPLC, and its chiroptical properties were examined with optical rotation and electronic circular dichroism (ECD) spectra. The title compound underwent photoracemization under daylight. This behavior was investigated in various solvents and compared with that of 1,3-bis(tetrathiafulvalenyl)allene (bis-TTF-allene) derivative 2. The first-order rate plot of the intensity of the ECD spectra at a given time interval gave the rate of racemization. Mild racemization was observed in polar solvents, whereas a relatively fast rate was obtained in less polar solvents. In addition, the TTF groups of the allene also accelerate the racemization rate. These results suggest that the racemization mechanism occurs via a non-polar diradical structure. Full article
(This article belongs to the Special Issue Dynamic Stereochemistry)
Figures

Open AccessArticle Influence of Temperature on the Enantioselectivity of Koga Tetraamines on Amylose Chiral Stationary Phases
Molecules 2014, 19(1), 9-21; doi:10.3390/molecules19010009
Received: 25 October 2013 / Revised: 4 December 2013 / Accepted: 10 December 2013 / Published: 19 December 2013
Cited by 2 | PDF Full-text (1261 KB) | HTML Full-text | XML Full-text
Abstract
Enantioseparation is largely based on the formation of transitional complexes, the solvation species, the stationary phase configurations or the diastereomeric complexes formed by analytes and the chiral stationary phase. Temperature and the chemical nature and composition of the eluent play significant roles during
[...] Read more.
Enantioseparation is largely based on the formation of transitional complexes, the solvation species, the stationary phase configurations or the diastereomeric complexes formed by analytes and the chiral stationary phase. Temperature and the chemical nature and composition of the eluent play significant roles during that process. In this study; unique temperature-induced behaviors were observed during the enantioseparation of Koga tetraamines, also known as Koga bases, on polysaccharide chiral stationary phases, in which van’t Hoff plots were acquired over a temperature range of 10 °C to 40 °C with 5 °C increments. Koga bases were eluted by a mixture of methanol and 2-propanol with 0.03% triethylamine as a modifier. The van’t Hoff plots are linear in the case of eluent containing equal volumes of methanol and 2-propanol. Increasing 2-propanol concentration from 50% to 85% in volume led to non-linear van’t Hoff plots over the entire temperature range studied. Examination of the individual non-linear plots revealed two linear regions of 10 °C–20 °C and 20 °C–40 °C. Transition from one linear region to the other at 20 °C indicates alterations of chiral stationary phase conformation and/or enantioseparation mechanism as a result of temperature changes. Full article
(This article belongs to the Special Issue Dynamic Stereochemistry)
Open AccessArticle Examination of the Potential for Adaptive Chirality of the Nitrogen Chiral Center in Aza-Aspartame
Molecules 2013, 18(12), 14739-14746; doi:10.3390/molecules181214739
Received: 3 October 2013 / Revised: 7 November 2013 / Accepted: 12 November 2013 / Published: 28 November 2013
Cited by 2 | PDF Full-text (465 KB) | HTML Full-text | XML Full-text
Abstract
The potential for dynamic chirality of an azapeptide nitrogen was examined by substitution of nitrogen for the α-carbon of the aspartate residue in the sweetener S,S-aspartame. Considering that S,S- and R,S-aspartame possess sweet and
[...] Read more.
The potential for dynamic chirality of an azapeptide nitrogen was examined by substitution of nitrogen for the α-carbon of the aspartate residue in the sweetener S,S-aspartame. Considering that S,S- and R,S-aspartame possess sweet and bitter tastes, respectively, a bitter-sweet taste of aza-aspartame 9 could be indicative of a low isomerization barrier for nitrogen chirality inter-conversion. Aza-aspartame 9 was synthesized by a combination of hydrazine and peptide chemistry. Crystallization of 9 indicated a R,S-configuration in the solid state; however, the aza-residue chiral center was considerably flattened relative to its natural amino acid counterpart. On tasting, the authors considered aza-aspartame 9 to be slightly bitter or tasteless. The lack of bitter sweet taste of aza-aspartame 9 may be due to flattening from sp2 hybridization in the urea as well as a high barrier for sp3 nitrogen inter-conversion, both of which may interfere with recognition by taste receptors. Full article
(This article belongs to the Special Issue Dynamic Stereochemistry)
Figures

Open AccessArticle Perfluoroalkanesulfonamide Organocatalysts for Asymmetric Conjugate Additions of Branched Aldehydes to Vinyl Sulfones
Molecules 2013, 18(12), 14529-14542; doi:10.3390/molecules181214529
Received: 30 October 2013 / Revised: 20 November 2013 / Accepted: 21 November 2013 / Published: 25 November 2013
Cited by 2 | PDF Full-text (393 KB) | HTML Full-text | XML Full-text
Abstract Asymmetric conjugate additions of branched aldehydes to vinyl sulfones promoted by sulfonamide organocatalyst 6 or 7 have been developed, allowing facile synthesis of the corresponding adducts with all-carbon quaternary stereocenters in excellent yields with up to 95% ee. Full article
(This article belongs to the Special Issue Dynamic Stereochemistry)
Open AccessArticle Deracemization of Axially Chiral Nicotinamides by Dynamic Salt Formation with Enantiopure Dibenzoyltartaric Acid (DBTA)
Molecules 2013, 18(11), 14430-14447; doi:10.3390/molecules181114430
Received: 15 October 2013 / Revised: 13 November 2013 / Accepted: 19 November 2013 / Published: 21 November 2013
Cited by 3 | PDF Full-text (1560 KB) | HTML Full-text | XML Full-text
Abstract
Dynamic atroposelective resolution of chiral salts derived from oily racemic nicotinamides and enantiopure dibenzoyltartaric acid (DBTA) was achieved by crystallization. The absolute structures of the axial chiral nicotinamides were determined by X-ray structural analysis. The chirality could be controlled by the selection of
[...] Read more.
Dynamic atroposelective resolution of chiral salts derived from oily racemic nicotinamides and enantiopure dibenzoyltartaric acid (DBTA) was achieved by crystallization. The absolute structures of the axial chiral nicotinamides were determined by X-ray structural analysis. The chirality could be controlled by the selection of enantiopure DBTA as a chiral auxiliary. The axial chirality generated by dynamic salt formation was retained for a long period after dissolving the chiral salt in solution even after removal of the chiral acid. The rate of racemization of nicotinamides could be controlled based on the temperature and solvent properties, and that of the salts was prolonged compared to free nicotinamides, as the molecular structure of the pyridinium ion in the salts was different from that of acid-free nicotinamides. Full article
(This article belongs to the Special Issue Dynamic Stereochemistry)
Figures

Open AccessArticle Conformational Analysis of Geometric Isomers of Pitavastatin Together with Their Lactonized Analogues
Molecules 2013, 18(11), 13283-13296; doi:10.3390/molecules181113283
Received: 24 September 2013 / Revised: 17 October 2013 / Accepted: 19 October 2013 / Published: 28 October 2013
Cited by 4 | PDF Full-text (899 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Super-statins are synthetic inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, which is the rate-limiting enzyme responsible for the biosynthesis of cholesterol. All of the super-statins with a C=C double bond spacer between the heterocyclic and the dihydroxycarboxylic moiety that are currently on the market exist
[...] Read more.
Super-statins are synthetic inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, which is the rate-limiting enzyme responsible for the biosynthesis of cholesterol. All of the super-statins with a C=C double bond spacer between the heterocyclic and the dihydroxycarboxylic moiety that are currently on the market exist as E-isomers. To extend the understanding of conformational and thermodynamic preferences of Z-isomeric super-statin analogues, this study focused on analyzing pitavastatin and its lactonized derivatives via NMR spectroscopy and ab initio calculations. Z-isomeric pitavastatin analogues exist in solution as a pair of interconverting rotamers, where the Gibbs free energies between the major and minor rotamers are within 0.12 and 0.25 kcal mol−1 and the rotational energy barriers are between 15.0 and 15.9 kcal mol−1. The analysis of long-range coupling constants and ab initio calculations revealed that rotation across the C5'–C7 single bond is essential for generating a pair of atropisomers. The overall comparison of the results between Z-isomeric pitavastatin and rosuvastatin analogues demonstrated that the former are to some extent more flexible to attain numerous conformations. Demonstrating how structural differences between super-statin analogues induce distinctive conformational preferences provides important insight into the super-statins’ conformational variability and may well improve future drug design. Full article
(This article belongs to the Special Issue Dynamic Stereochemistry)
Figures

Open AccessArticle Characterization of Amide Bond Conformers for a Novel Heterocyclic Template of N-acylhydrazone Derivatives
Molecules 2013, 18(10), 11683-11704; doi:10.3390/molecules181011683
Received: 4 August 2013 / Revised: 10 September 2013 / Accepted: 13 September 2013 / Published: 25 September 2013
Cited by 16 | PDF Full-text (970 KB) | HTML Full-text | XML Full-text
Abstract
Herein we describe NMR experiments and structural modifications of 4-methyl-2-phenylpyrimidine-N-acylhydrazone compounds (aryl-NAH) in order to discover if duplication of some signals in their 1H- and 13C-NMR spectra was related to a mixture of imine double bond stereoisomers (E/Z
[...] Read more.
Herein we describe NMR experiments and structural modifications of 4-methyl-2-phenylpyrimidine-N-acylhydrazone compounds (aryl-NAH) in order to discover if duplication of some signals in their 1H- and 13C-NMR spectra was related to a mixture of imine double bond stereoisomers (E/Z) or CO-NH bond conformers (syn and anti-periplanar). NMR data from NOEdiff, 2D-NOESY and 1H-NMR spectra at different temperatures, and also the synthesis of isopropylidene hydrazone revealed the nature of duplicated signals of a 4-methyl-2-phenylpyrimidine-N-acylhydrazone derivative as a mixture of two conformers in solution. Further we investigated the stereoelectronic influence of substituents at the ortho position on the pyrimidine ring with respect to the carbonyl group, as well as the electronic effects of pyrimidine by changing it to phenyl. The conformer equilibrium was attributed to the decoplanarization of the aromatic ring and carbonyl group (generated by an ortho-alkyl group) and/or the electron withdrawing character of the pyrimidine ring. Both effects increased the rotational barrier of the C-N amide bond, as verified by the DG values calculated from dynamic NMR. As far as we know, it is the first description of aryl-NAH compounds presenting two CO-NH bond- related conformations. Full article
(This article belongs to the Special Issue Dynamic Stereochemistry)

Review

Jump to: Research

Open AccessReview Stereocontrolled Synthesis and Functionalization of Cyclobutanes and Cyclobutanones
Molecules 2013, 18(12), 15541-15572; doi:10.3390/molecules181215541
Received: 7 November 2013 / Revised: 9 December 2013 / Accepted: 11 December 2013 / Published: 13 December 2013
Cited by 25 | PDF Full-text (423 KB) | HTML Full-text | XML Full-text
Abstract
In the last decade a certain number of new cyclobutane and cyclobutanone synthesis and functionalization protocols have been published. Organo- and biocatalyzed eco-friendly approaches to cyclobutane-containing molecules have been developed with interesting results. Also, successful new total synthesis of bioactive compounds and drugs
[...] Read more.
In the last decade a certain number of new cyclobutane and cyclobutanone synthesis and functionalization protocols have been published. Organo- and biocatalyzed eco-friendly approaches to cyclobutane-containing molecules have been developed with interesting results. Also, successful new total synthesis of bioactive compounds and drugs have been recently reported where a four membered ring represented the key intermediate. Therefore, the rising interest in this field represents a great point of discussion for the scientific community, disclosing the synthetic potential of strained four membered ring carbocyclic compounds. Herein we report a critical survey on the literature concerning the enantiocontrolled synthesis and functionalization of cyclobutane derivatives, with particular attention to metal-free, low impact methodologies, published during the period 2000–2013. Full article
(This article belongs to the Special Issue Dynamic Stereochemistry)

Journal Contact

MDPI AG
Molecules Editorial Office
St. Alban-Anlage 66, 4052 Basel, Switzerland
molecules@mdpi.com
Tel. +41 61 683 77 34
Fax: +41 61 302 89 18
Editorial Board
Contact Details Submit to Molecules
Back to Top