Self-disproportionation of enantiomers via achiral gravity-driven column chromatography: A case study of N -acyl-α-phenylethylamines

Possible Case of Halogen Bond‐Driven Self‐Disproportionation of Enantiomers (SDE) via Achiral Chromatography

“…With this in mind, we set out to experiment with enantiomerically enriched mebroqualone ( P )‐ 1 f as a model compound, simply because it was available in a sufficiently large quantity. Based on previous experience,– we chose to start with the concentration 1 mmol of 1 f for 40 g of silica gel, and selecting the eluent, we adjusted the ratio of n ‐hexane/EtOAc (6:1) providing R f ≈0.2 (TLC) for a suitable elution rate. Under these conditions, mebroqualone analog 1 f did show an noticeable magnitude of SDE, but the difference between the highest and lowest value of ee , defined as Δ ee , as well the enantiomeric enrichment of the first fractions, were not high enough for any practical applications (Δ ee =12.4, Table , entry 1).…”

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.…”

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

“…[40,41] Thea bility of an amide bond to serve as ad onor and/ or as an acceptor in an HB is also of key importance in the SDE phenomenon, resulting from the formation of homo-/heterochirals pecies.H ence, ourr ecent research has demonstratedt hat sulfur-for-oxygen substitution in an amide group has ar emarkably detrimental effect on the SDE magnitude of the corresponding chiral derivatives. [42] Thus,S DE via achiralc hromatography of chiral ÀC(S)À NHÀ derivatives resulted in only slightly enantiomerically enriched/depleted fractions, which can be explained by the inabilityo ft he sulfur atom to support the HB.…”

“…TheS DE phenomenon waso bserved for all amides 8. [42][43][44][45] Similarly to CF 3 -containing amides,t he magnitude of the SDE in these cases strongly depended on the solvent system used. Table 3p resents the results obtained for amide 8a in different eluents.…”

“…[43] Thes teric and electronic effects of the substituentso n the acyl group on the SDE phenomenon were also investigated. [42] Thea mides 8b-8e were used to studyt he effect of steric requirements,w hile the amides 8f-8g were used to study the electronic effect. Thec omparison of the SDE of these derivatives was done under the same chromatographic conditions.T he silica gel wasu sed as as tationary phase in the proportion of 1mmol of the amide to 30 gramso fthe phase,a nd the most effective eluent found for amide 8a was am ixture of c-hexanew ith MTBE.…”