Effects of solvent on inclusion complexation of a chiral dipeptide toward racemic BINOL

Abstract

The effects of reaction solvent on inclusion complexation of a chiral dipeptide (3S,6S)-1 derived from (S)-proline toward racemic BINOL was investigated, discovering that the reaction solvent played a crucial role in determining the inclusion complexation behavior of dipeptide (3S,6S)-1 toward rac-BINOL. (3S,6S)-1 did not show any chiroselective or achiroselective complexation toward rac-BINOL in polar protic solvents such as methanol and ethanol, polar aprotic solvents including trichloromethane and THF, while in polar aprotic solvent ethyl acetate and apolar aprotic solvents benzene, (3S,6S)-1 displayed achiroselective complexation toward rac-BINOL. However, the resulting heterocomplex HC-2 from benzene and HC-3 from ethyl acetate have a different composition. Single crystal X-ray diffraction analysis demonstrates that the two heterocomplexes are formed via different H-bond interaction patterns, in which the reaction solvent has a dramatic effect. Furthermore, this work provides a relatively green method for quantitative enantiomeric enrichment of nonracemic BINOL, in which unacceptable and toxic benzene was replaced by ethyl acetate.

Methodology for the Absolute Configuration Determination of Epoxythymols Using the Constituents of Ageratina glabrata

“…In the five compounds ( 1 – 5 ) studied, it was observed that the changes in chemical shifts upon addition of BINOL were more significant on those hydrogen atoms located near the stereogenic center, in concordance with the observed trends for other substances. − , In some cases, intermolecular interactions between BINOL and the studied molecules have been confirmed by X-ray diffraction analysis. On the basis of these findings, the formation of a transitory hydrogen bond between the hydroxy hydrogen of ( S )-BINOL and the oxygen atoms O-10 and/or O-8 of the epoxythymols could be proposed, allowing an evident shielding phenomenon at the CH 2 -10 and CH 2 -9 hydrogen atoms caused by the naphthol moieties.…”

“…To achieve this task, it was decided to explore the use of ( S )-1,1′-bi-2-naphthol [( S )-BINOL] as a chiral solvating agent to differentiate the enantiomers by means of 1 H NMR measurements. This method has been employed successfully in the enantiomeric discrimination of some natural isoflavanones, alkaloids, , and peptides, as well as for pharmacologically active principles − and is based on the use of a chiral solvating agent for the enantioresolution of the NMR signals of two distereoisomeric host–guest complexes formed between a BINOL enantiomer and each enantiomer of the studied thymol derivative. This methodology has some advantages over other spectroscopic techniques for the estimation of the enantiomeric excess.…”

An Efficient Method for Long‐Term Configurational Stabilization of Chiral Tricyclic Dipeptide via Heterocomplexation Approach

“…Further studies found that chiral tricyclic dipeptide, (5a S ,10a S )‐octahydro‐5H,10H‐dipyrrolo[1,2‐a:1′,2′‐d]pyrazine‐5,10‐dione, ( S , S )‐ 1 could undergo heterocomplexation with racemic 1,1′‐bi‐2‐naphthol (BINOL) and 2,3‐O‐cyclohexylidene‐1,1,4,4‐tetraphenylthreitol ( 2 ) derived from L ‐tartaric acid. Furthermore, this heterocomplexation strategy has been successfully applied to the enantiomeric enrichment of nonracemic BINOL and chiral diol 2…”