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

Abstract

This article is based on a review of literature devoted to the phenomenon of SDE via achiral chromatography since the appearance of the seminal work of Professor Emanuel Gil‐Av. The discussed examples of chromatographic studies are related to amides derived from chiral amines and α‐ and β‐amino acids. We discuss the observed SDE magnitude as a function of a compound's structure, and composition of eluent and stationary phases, providing some mechanistic considerations. Particular emphasis is given to the aspect of SDE via achiral chromatography as an emerging unconventional enantiomeric purification technique.

Recommended Tests for the Self-Disproportionation of Enantiomers (SDE) to Ensure Accurate Reporting of the Stereochemical Outcome of Enantioselective Reactions

“…The SDE literature has been well reviewed previously, including generally [ 5 , 47 ], for particular processes, e.g., sublimation [ 54 ] and chromatography [ 45 , 46 , 78 , 122 ], as well as for specific SDE-phoric groups, e.g., sulfoxides [ 71 , 102 ], fluorine-containing compounds [ 86 , 87 , 123 , 124 , 125 ], amides [ 102 , 126 ], and amino acids and their derivatives [ 105 ]. Of note, SDEvS has been much less reported, for the obvious reason that it is simply a less utilized technique compared to chromatography for routine purification.…”

“…The first instances of SDEvC were independently discovered by Cundy and Crooks [ 134 ] in 1983, and a year later in 1984 by Charles and Gil-Av [ 25 ], their discoveries coinciding with the beginning of wide availability of HPLC instrumentation and improved sensitivity of analyte detection. Details of these pioneering papers can be found in the following review articles [ 5 , 6 , 78 , 126 ]. For the purposes of the present account, we discuss a few examples dealing with routine, gravity-driven column chromatography, since it is routinely used in virtually all research laboratories for the isolation and purification of reaction products.…”

Self-disproportionation of enantiomers (SDE) of chiral sulfur-containing compounds via achiral chromatography

“…90 ), clearly indicate that the relatively strong SDE phenomenon should be observed as a rule when a chiral sulfoxide is subjected to achiral gravity-driven chromatography. This means that the sulfinyl moiety should be considered as a SDE-phoric group 18,103 along with chiral amides 31,[51][52][53][54][55]102 and fluorine-containing compounds. 33,[56][57][58][59][60][61] Thus, it may now be a suitable time to consider addition, in papers dealing with asymmetric synthesis of sulfoxides, information regarding the magnitude of the SDE phenomenon during a gravity-derived chromatographic purification.…”

“…[43][44][45][46][47][48][49][50] The results of these experimental studies and theoretical calculations allow the formulation of the concept of the SDE-phoric groups as a structural element responsible for the occurrence of the SDE during achiral chromatography. [51][52][53][54][55][56][57][58][59][60][61] Considering the structure of the SDE-phoric moieties one can expect interesting properties for a chiral sulfinyl grouping or a chiral thioamide residue. This results from the ability that compounds containing these groups have to form homo-and heterochiral dimers or higher-order aggregates by dipole-dipole interactions and/or hydrogen bonds.…”

The self‐disproportionation of enantiomers (SDE): The effect of scaling down, potential problems versus prospective applications, possible new occurrences, and unrealized opportunities?

“…In spite of the SDE being well‐documented and a large number of examples being described in several fine reviews on the phenomenon involving processes other than recrystallization, nevertheless, it remains that the SDE phenomenon is not widely appreciated by researchers, at least for processes other than recrystallization. The reviews on the SDE phenomenon include general accounts of the SDE phenomenon, as well as one general review specific for fluorine‐containing compounds , another dedicated to SDE via sublimation , as well as several dedicated solely to the SDE via achiral chromatography . Here in this commentary, the focus is on chromatographic techniques, especially with regards to, those techniques of wide application and interest for the readership of Electrophoresis .…”