Atropisomerism in 3-arylthiazolidine-2-thiones. A combined dynamic NMR and dynamic HPLC study

Ciogli, Alessia; Kumar, Sundaravel Vivek; Mancinelli, Michele; Mazzanti, Andrea; Perumal, S.; Severi, Caterina; Villani, Claudio

doi:10.1039/c6ob02145j

Cited by 22 publications

(14 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A domino reaction between aryl‐isocyanates and 1,4‐dithiane‐2,5‐diol was used for the synthesis of axially chiral N‐arylthiazolinethione derivatives 28 (Scheme ) . The more flexible five‐membered ring of arylthiazolidine‐2‐thiones implies more flexibility in the transition state, thus lower rotational barriers at the C sp 2 ‐nitrogen stereogenic axis.…”

Section: Atropisomerismmentioning

confidence: 99%

Stereochemistry and Recent Applications of Axially Chiral Organic Molecules

et al. 2020

Self Cite

View full text Add to dashboard Cite

This minireview covers the literature of the last decade related to the stereochemistry of axially chiral molecules. The first section reviews the use of dynamic NMR and dynamic HPLC for the ranking of the steric size of common organic moieties. The second and third sections describe the recent advances in the preparation of new atropisomeric scaffolds, and in the asymmetric synthesis of stereogenic axes by means of atroposelective organocatalysis.

show abstract

Section: Atropisomerismmentioning

confidence: 99%

Stereochemistry and Recent Applications of Axially Chiral Organic Molecules

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…In 2016, Ciogli, Mazzanti, and Perumal exploited a new domino reaction between aryl isocyanates 12 and commercially available 1,4‐dithiane‐2,5‐diol for the synthesis of axially chiral N ‐arylthiazolinethione derivatives 14 (Scheme ) . A complete combined dynamic NMR and HPLC study both of the transient hemiaminal intermediates 13 and of the N ‐arylthiazolinethiones 14 allowed the determination of a low barrier to rotation of 90.5 kJ mol –1 for R = H, in agreement with fast atropisomerization at room temperature.…”

Section: Non‐stereoselective Synthesesmentioning

confidence: 99%

A Bird's Eye View of Atropisomers Featuring a Five‐Membered Ring

2018

View full text Add to dashboard Cite

An atropisomer is a member of a subclass of restricted rotational conformers – this restricted rotation giving rise to stereogenic sigma bonds – that can be isolated as separate chemical species. Most atropisomer are six‐membered‐ring biaryl or heterobiaryl derivatives. The aim of this microreview is to shed light on a less common class of atropisomers, those containing at least one five‐membered hetero‐ or carbocycle and displaying variously a stereogenic C–N, C–C, or even N–N chemical bond. After a short introduction, the occurrence of atropisomers in nature is presented, as well as the synthetic efforts – encompassing non‐stereoselective and diastereoselective strategies, together with an update on very recent enantioselective approaches – devoted to such axially chiral compounds. Finally, a special focus is placed on their important utilization as original and efficient ligands for metal complexes.

show abstract

“…Dynamic NMR and dynamic HPLC (coupled with computational techniques) are two of the most common methods to measure the free energy of interconversion between stereoisomers [26][27][28][29][30][31][32][33]. Dynamic HPLC with chiral stationary phase (CSP) is successfully employed in the determination of the enantiomerization barriers of fast interconverting enantiomers that exchange on a time-scale comparable to that of the separation process.…”

Section: Introductionmentioning

confidence: 99%

Low Temperature Dynamic Chromatography for the Separation of the Interconverting Conformational Enantiomers of the Benzodiazepines Clonazolam, Flubromazolam, Diclazepam and Flurazepam

2021

Self Cite

View full text Add to dashboard Cite

Benzodiazepines (BZDs) are an important class of psychoactive drugs with hypnotic-sedative, myorelaxant, anxiolytic and anticonvulsant properties due to interaction with the GABAa receptor in the central nervous system of mammals. BZDs are interesting both in clinical and forensic toxicology for their pharmacological characteristics and potential of abuse. The presence of a non-planar diazepine ring generates chiral conformational stereoisomers, even in the absence of stereogenic centers. A conformational enrichment of BZD at the binding sites has been reported in the literature, thus making interesting a stereodynamic screening of a wide range of BZDs. Herein, we report the investigation of three stereolabile 1,4-benzodiazepine included in the class of “designer benzodiazepines” (e.g., diclazepam, a chloro-derivative of diazepam, and two triazolo-benzodiazepines, flubromazolam and clonazolam) and a commercially available BZD known as flurazepam, in order to study the kinetic of the “ring-flip” process that allows two conformational enantiomers to interconvert at high rate at room temperature. A combination of low temperature enantioselective dynamic chromatography on chiral stationary phase and computer simulations of the experimental chromatograms allowed us to measure activation energies of enantiomerization (ΔG‡) lower than 18.5 kcal/mol. The differences between compounds have been correlated to the pattern of substitutions on the 1,4-benzodiazepinic core.

show abstract

Atropisomerism in 3-arylthiazolidine-2-thiones. A combined dynamic NMR and dynamic HPLC study

Cited by 22 publications

References 66 publications

Stereochemistry and Recent Applications of Axially Chiral Organic Molecules

Stereochemistry and Recent Applications of Axially Chiral Organic Molecules

A Bird's Eye View of Atropisomers Featuring a Five‐Membered Ring

Low Temperature Dynamic Chromatography for the Separation of the Interconverting Conformational Enantiomers of the Benzodiazepines Clonazolam, Flubromazolam, Diclazepam and Flurazepam

Contact Info

Product

Resources

About