Combining Diastereomeric Resolution and Viedma Ripening by Using a Racemic Resolving Agent. Issue 44 (22nd October 2021)

• Record Type: Journal Article
• Authors: Lerdwiriyanupap, Tharit; Belletti, Giuseppe; Tinnemans, Paul; Meekes, Hugo; Rutjes, Floris P. J. T.; Vlieg, Elias; Flood, Adrian E.
• Is Part Of: European journal of organic chemistry. Issue 44(2021)
• Page Start: 5975
• Page End: 5980
• Publication Date: 2021-10-22
• Subjects: Chiral resolution -- Chirality -- Diastereomeric resolution -- Racemization -- Stereoisomer -- Viedma ripening; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.202101193
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract: In spite of the many resolution techniques available to separate enantiomers, diastereomeric resolution still remains the most widely used technique in industry. However, drawbacks of this technique are the limited yield of the desired enantiomer and the expensive enantiopure resolving agent that is required. We show here for the first time that a combination of diastereomeric resolution with Viedma ripening using a racemic resolving agent can also provide a single stereoisomer when using an excess of the racemic resolving agent, without the need for the resolving agent to racemize. The requirements of this process are, like for an enantiomeric system, that the compound crystallizes as a racemic conglomerate and that at least one chiral center in the target molecule is racemizable. In addition, owing to the presence of the racemization reaction, substantial improvement in the yield can be obtained. We here demonstrate this approach using a metastable conglomerate salt of rac ‐2‐phenylglycinamide with rac ‐ N ‐acetyl tryptophan. Abstract : Combination of diastereomeric resolution with Viedma ripening achieves a single stereoisomeric salt from racemic mixtures of two compounds. The process allows for higher yield of the product in comparison with traditional diastereomeric resolution while using a lower‐cost racemic mixture of the resolving agent. The successful example is demonstrated using a racemic conglomerate salt of rac ‐2‐phenylglycinamide with rac ‐ N ‐acetyl tryptophan.