Chiral Resolution of Racemic 2‐Pyrone Diels‐Alder Cycloadduct by Diastereomeric Salt Formation

Jeon, Tae Hong; Kang, Hyung Joon; Svirid, Anastasia; Lyakhov, Alexander S.; Kovalenko, V. N.; Cho, Cheon Gyu

doi:10.1002/bkcs.11838

Cited by 4 publications

(9 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The behavior of diastereomeric salts we observed here is not common according to our experience 1,11–15 and among a huge number of known resolution procedures. Usually, the treatment of racemate with a resolving reagent results in a pair of salts with different solubility (crystallinity).…”

Section: Resultsmentioning

confidence: 63%

“…Racemic ester 4 was synthesized from 5‐bromo‐3‐phenyl‐α‐pyrone 3 6,7 according to our procedure developed for similar dibromo derivative 1 . Purification of the crude material by crystallization from the mixture of tert ‐butyl methyl ether and hexane provided 4 as a single endo ‐stereoisomer.…”

Section: Methodsmentioning

confidence: 99%

“…Diels‐Alder chemistry applied to α‐pyrones allowed to construct a bicyclolactone backbone of syntactically challenging metabolites such as basiliolides, 3 transtaganolides, 3,4 or scholarisine 5 . Furthermore, bicyclic compounds can serve as a source of functionalized cyclohexenes due to the cleavable lactone bond 1,2 . The advantage of this approach is a control of the relative stereochemistry of several simultaneously formed chiral centers in a Diels‐Alder adduct.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Resolution by diastereomeric salts: Access to both enantiomers of racemic acid using the same enantiomer of resolving base

Kovalenko

Císařová

2023

Chirality

Self Cite

View full text Add to dashboard Cite

Racemic carboxylic acid, a Diels‐Alder cycloadduct derived from 5‐bromo‐3‐phenyl‐α‐pyrone and acrylate dienophile, was resolved into enantiomers by diastereomeric salt crystallization. Quinidine was used as a sole resolving base. The salt of (+)‐acid crystallized from aqueous acetonitrile solution. Once this salt was separated by filtration, quinidine salt with (−)‐acid crystallized from mother liquor. As a result, both enantiomers of Diels‐Alder cycloadduct were isolated in high enantiomeric purity.

show abstract

Section: Resultsmentioning

confidence: 63%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Resolution by diastereomeric salts: Access to both enantiomers of racemic acid using the same enantiomer of resolving base

Kovalenko

Císařová

2023

Chirality

Self Cite

View full text Add to dashboard Cite

show abstract

“…An approach to obtain products with high enantiomeric purity is to utilize crystallization procedures. , Diastereomeric crystallization is commonly applied to separate racemic mixtures of chiral compounds also on the industrial scale. Depending on the difference in solubility of a pair of diastereomeric salts derived from a racemate and a chiral enantiopure resolving agent, one of the diastereomeric salts can be purified by repeated re-crystallization, and the subsequent decomposition of the purified diastereomeric salt provides one of the enantiomers of the racemate in a pure form. − An advantage of this method is that the enantiopurity may be improved by repeated re-crystallization of the less-soluble diastereomeric salt. The main disadvantage is that the corresponding more-soluble diastereomeric salt may be difficult to purify, and additional operations are required to obtain it.…”

Section: Trends In Enantioselective Recognition In Natural and Synthe...mentioning

confidence: 99%

Recognition in the Domain of Molecular Chirality: From Noncovalent Interactions to Separation of Enantiomers

2022

View full text Add to dashboard Cite

It is not a coincidence that both chirality and noncovalent interactions are ubiquitous in nature and synthetic molecular systems. Noncovalent interactivity between chiral molecules underlies enantioselective recognition as a fundamental phenomenon regulating life and human activities. Thus, noncovalent interactions represent the narrative thread of a fascinating story which goes across several disciplines of medical, chemical, physical, biological, and other natural sciences. This review has been conceived with the awareness that a modern attitude toward molecular chirality and its consequences needs to be founded on multidisciplinary approaches to disclose the molecular basis of essential enantioselective phenomena in the domain of chemical, physical, and life sciences. With the primary aim of discussing this topic in an integrated way, a comprehensive pool of rational and systematic multidisciplinary information is provided, which concerns the fundamentals of chirality, a description of noncovalent interactions, and their implications in enantioselective processes occurring in different contexts. A specific focus is devoted to enantioselection in chromatography and electromigration techniques because of their unique feature as “multistep” processes. A second motivation for writing this review is to make a clear statement about the state of the art, the tools we have at our disposal, and what is still missing to fully understand the mechanisms underlying enantioselective recognition.

show abstract

“…Up to now, formation of diastereomeric salt [23][24][25][26][27] and chiral chromatography [28][29][30][31] are two commonly applied chiral resolution methods in industry. For those compounds of interest that are easy to form salts, the formation of diastereomeric salt is the most suitable method, as a chiral resolving agent can form a pair of diastereomer salts with two enantiomers that show difference in their physical properties, promoting the success of the resolution [32].…”

Section: Introductionmentioning

confidence: 99%

Resolution of Halogenated Mandelic Acids through Enantiospecific Co-Crystallization with Levetiracetam

Wang

Peng

2021

Molecules

View full text Add to dashboard Cite

The resolution of halogenated mandelic acids using levetiracetam (LEV) as a resolving agent via forming enantiospecific co-crystal was presented. Five halogenated mandelic acids, 2-chloromandelic acid (2-ClMA), 3-chloromandelic acid (3-ClMA), 4-chloromandelic acid (4-ClMA), 4-bromomandelic acid (4-BrMA), and 4-fluoromandelic acid (4-FMA), were selected as racemic compounds. The effects of the equilibrium time, molar ratio of the resolving agent to racemate, amount of solvent, and crystallization temperature on resolution performance were investigated. Under the optimal conditions, the resolution efficiency reached up to 94% and the enantiomeric excess (%e.e.) of (R)-3-chloromandelic acid was 63%e.e.. All five halogenated mandelic acids of interest in this study can be successfully separated by LEV via forming enantiospecific co-crystal, but the resolution performance is significantly different. The results showed that LEV selectively co-crystallized with S enantiomers of 2-ClMA, 3-ClMA, 4-ClMA, and 4-BrMA, while it co-crystallized with R enantiomers of 4-FMA. This indicates that the position and type of substituents of racemic compounds not only affect the co-crystal configuration, but also greatly affect the efficiency of co-crystal resolution.

show abstract

Chiral Resolution of Racemic 2‐Pyrone Diels‐Alder Cycloadduct by Diastereomeric Salt Formation

Abstract: An efficient protocol was developed that allows resolution of racemic bicyclolactone carboxylic acid obtained from the Diels-Alder cycloaddition of 3,5-dibromo-2-pyrone by formation of diastereomeric salts with quinidine and cinchonidine.

Cited by 4 publications

References 58 publications

Resolution by diastereomeric salts: Access to both enantiomers of racemic acid using the same enantiomer of resolving base

Resolution by diastereomeric salts: Access to both enantiomers of racemic acid using the same enantiomer of resolving base

Recognition in the Domain of Molecular Chirality: From Noncovalent Interactions to Separation of Enantiomers

Resolution of Halogenated Mandelic Acids through Enantiospecific Co-Crystallization with Levetiracetam

Contact Info

Product

Resources

About