Determination of barriers to rotation of axially chiral 5‐methyl‐2‐(o‐aryl)imino‐3‐(o‐aryl)thiazolidine‐4‐ones

Abstract

Thermally interconvertible axially chiral 5-methyl-2-(o-aryl)imino-3-(o-aryl)-thiazolidine-4-ones have been synthesized diastereoselectively, and conformations of the major and minor enantiomeric pairs have been determined by (1)H nuclear magnetic resonance. Chromatographic resolutions of each compound have been performed by enantioselective high-performance liquid chromatography, and the barriers to rotation about the N(3)-C(aryl) bond have been determined by following the thermal interconversion process of the major to minor isomers until equilibrium. The rotational barriers range from 96.2 to 115.2 kJ/mol, depending on the size of ortho substituent on N(3)-aryl ring.

Spontaneous transfer of chirality in an atropisomerically enriched two-axis system

“…The dynamics described above for amide isomerization correspond to experimentally derived free energies barriers 17,18 of 24.8 kcal/mol ( trans -to- cis ) and 24.1 kcal/mol ( cis -to- trans ) (Figure 5; see Supplementary Information, Section VIII). Computations 19,20 provided free energy barriers of 24.4 kcal/mol ( trans -to- cis ) and 24.0 kcal/mol ( cis -to- trans ) respectively (Supplementary Information, Section XIII), on par with both the experimentally determined values and literature values for somewhat related compounds.…”

Stereochemical Investigations of DiastereomericN-[2-(Aryl)-5-methyl-4-oxo-1,3-thiazolidine-3-yl]-pyridine-3-carboxamides by Nuclear Magnetic Resonance Spectroscopy (1D and 2D)

“…Chiral compounds bearing thiazolidin-4-one ring have also been studied for their stereochemistry. Several studies have been done on these compounds regarding enantiodifferentiation of stereoisomers in the presence of chiral auxiliary [28], separation of enantiomers by chiral HPLC [29,30], and determination of absolute conformations [31,32].…”

Aldol Reactions of Axially Chiral 5-Methyl-2-(o-aryl)imino-3-(o-aryl)-thiazolidine-4-ones

“…Compounds 2 – 5 contain both a stereogenic center at C-5 of the heterocyclic ring and an axis of chirality [14] due to the hindered rotation around the N sp2 -C aryl bond and therefore exist as two diastereomeric pairs [13,15] (Scheme 2). The aldol reactions [16] of compounds 1 – 5 were carried out by treating the compounds with lithium diisopropyl amide (LDA) at −78 °C and followed by an electrophile quench with benzaldehyde (at −78 °C) (Scheme 1).…”

“…The aldol reactions were also carried out on compounds 3 , 4 and 5 having ortho OCH 3 , Cl and Br substituents, respectively. The steric requirement for the OCH 3 group is much lower than those of the Cl and Br, as evident from the barriers to hindered rotations caused by them as ortho substituents [13,14]. Therefore, although no selectivity was observed for the o -methoxy derivative, as the size of the ortho substituent increased, it was able to shield one face of the enolate.…”

“…We recently disclosed the diastereoselective synthesis of 2-( o -aryl)imino-3-( o -aryl)-5-methyl-thiazolidine-4-ones [13] (Scheme 1) bearing an axis of chirality and showed that they are conformationally and configurationally stable even at room temperature [13,14]. In this paper, we report the aldol reactions of 1 – 5 (Scheme 1) which were found to proceed via enolates possessing an axis of chirality, to produce chiral secondary carbinols separable by HPLC on a chiral sorbent.…”