In‐tube derivatization for determination of absolute configuration and enantiomeric purity of chiral compounds by NMR spectroscopy

• Published in: Magnetic resonance in chemistry Vol. 55; no. 4; pp. 269 - 273
• Main Authors: Gao, Jinhai, Rajan, Srinivasan, Wang, Bing
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.04.2017
• Subjects: absolute configuration; Alcohols; Coupling agents; Derivatives; enantiomeric purity; in‐tube derivatization; NMR; NMR spectroscopy; Nuclear magnetic resonance; polymer‐supported coupling agents; Purification; Purity; Tubes; in-tube derivatization; NMR; enantiomeric purity; absolute configuration; polymer-supported coupling agents
• ISSN: 0749-1581; 1097-458X
• DOI: 10.1002/mrc.4419

We have developed an in‐tube derivatization method using commercially available polymer‐supported coupling agents to prepare derivatives of chiral compounds directly in NMR tube with high yield and purity. Because the method does not require any workup or purification, the configuration and enatiopurity can be quickly determined by NMR analysis for a small amount of chiral compounds, which is critical for today's fast‐paced medicinal chemistry efforts in drug discovery. The application of the method was demonstrated for the derivatization of chiral amines, alcohols, diols, amino alcohols, thiols, and carboxylic acids using various chiral derivatizing agents and coupling agents. This article also serves as a practical guide for in‐tube derivatization and selection of suitable chiral derivatizing agents and coupling agents for various types of chiral compounds. Copyright © 2016 John Wiley & Sons, Ltd. A fast and efficient in‐tube derivatization method using commercially available polymer‐supported coupling agents was developed to prepare chiral derivatizing agent derivatives of chiral compounds directly in NMR tube without any workup or purification. The method allows quick NMR analysis of chiral compounds at microscale level.