The self-disproportionation of the enantiomers (SDE) of methyl n-pentyl sulfoxide via achiral, gravity-driven column chromatography: a case study

Abstract

This work explores the self-disproportionation of enantiomers (SDE) of chiral sulfoxides via achiral, gravity-driven column chromatography using methyl n-pentyl sulfoxide as a case study. A major finding of this work is the remarkable persistence and high magnitude of the SDE for the analyte. Thus, it is the first case where SDE is observed even in the presence of MeOH in the mobile phase. The study demonstrated the practical preparation, in line with theory, of enantiomerically pure (>99.9% ee) samples of methyl n-pentyl sulfoxide starting from a sample of only modest ee (<35%). Remarkably, it was found that the order of elution was inverted, i.e. enantiomerically depleted fractions preceded later eluting enantiomerically enriched ones, when the stationary phase was changed from silica gel to aluminum oxide. To the best of our knowledge, this is the first occurrence of inverted SDE behavior due solely to a change in the stationary phase. Aberrant SDE behavior was observed in that the ee did not always fall continuously during the progression of the chromatography, and this was attributed to the complexity of the system at hand which cannot be described in simple terms such as the formation only of homo- and heterochiral dimers based on a single interaction. The results nevertheless suggest that all compounds with a chiral sulfoxide moiety in their structure are likely to exhibit the SDE phenomenon and thus this work constitutes the first example of SDE predictability. Moreover, it could well be that optical purification based on the SDE phenomenon is a simple, convenient, and inexpensive method for the optical purification of this class of compounds with a high degree of proficiency.

A comprehensive examination of the self-disproportionation of enantiomers (SDE) of chiral amides via achiral, laboratory-routine, gravity-driven column chromatography

“…For this test we used arbitrary conditions derived from our previous experience with the SDE study of chiral sulfoxides. 17 The rst test run fully realized our worries; thus, compound 1, of 72.3% ee, when subjected to routine column chromatography yielded initial fractions highly enriched in the excess enantiomer (>93% ee) while the nal fractions were alternatively drastically depleted in the excess enantiomer (<45% ee). One may agree that this experiment underscores the scientic signicance of this study and its general importance for organic chemistry and asymmetric synthesis.…”

Self‐disproportionation of Enantiomers (SDE) of Chiral Nonracemic Amides via Achiral Chromatography

“…The number and variety of the reported examples evidently suggests that a relatively strong SDE magnitude will be observed in virtually any case where a chiral amide is subjected to achiral chromatography. These overwhelming data clearly identify an amide functionality as an SDE‐phoric group, along with chiral sulfoxides and fluorine‐containing compounds ,,. Thus, it would be reasonable to expect that the editorial policy of chemistry journals should include the request to perform a proper SDE test for papers dealing with catalytic chemical or enzymatic asymmetric synthesis of amide, fluorine, and sulfoxide group‐containing compounds .…”

The resolution of acyclic P‐stereogenic phosphine oxides via the formation of diastereomeric complexes: A case study on ethyl‐(2‐methylphenyl)‐phenylphosphine oxide

“…[7][8][9] In those reactions, (−)-menthol and (−)-ephedrine are frequently used chiral templates, 6,10-17 but other synthetic derivatives were also used. The self-disproportion of enantiomeric mixtures via achiral chromatography or sublimation is receiving more and more attention, [22][23][24][25][26] but the first example of this phenomenon in the sphere of P-stereogenic compounds is yet to be published. However, in this case, the purification of the enantiomeric mixtures should be an integral part of these procedures.…”