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

Abstract

This work explores the self-disproportionation of enantiomers (SDE) of chiral amides via achiral, gravitydriven column chromatography as typically used in laboratory settings. The major findings of this work are: (1) the remarkable persistence and high magnitude of the SDE for the analytes under a variety of conditions, including polar solvents and different achiral stationary phases and (2) the notable generality of the SDE phenomenon as it occurs for a wide range of chiral amide substrates and even for a broad range of starting ee. This last aspect is unusual and not commonly observed. The key conclusion of this work is that it judiciously conveys the predictability of the SDE for chiral amides under the routine conditions of achiral chromatography. These results are consequently of concern for practitioners in the area of catalytic asymmetric synthesis involving chiral amides as intermediates or products and the inferents need to be taken extremely seriously by workers in the field.

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.…”

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

“…The structures of N ‐acetylated 1‐phenylethylamines used in the studies on SDE via gravity‐driven column chromatography are depicted in Figure . The SDE phenomenon was observed for all amides 8 …”

“…Another factor which affects the SDE phenomenon under chromatographic conditions is the type of stationary phase. Table includes results obtained for amides 8a , which have a methyl group; 8c , which have a sterically demanding i Pr group; and 8f , which have an electron‐donating OMe group …”

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.…”