The use of MPA amide for the assignment of absolute configuration of a sterically hindered cyclic secondary amine by ‘mix and shake’ NMR method

✍ Scribed by Jinhai Gao; Hansjoerg Haas; Kate Yaping Wang; Zhuoliang Chen; Werner Breitenstein; Srinivasan Rajan

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 377 KB
• Volume: 46
• Category: Article
• ISSN: 0749-1581
• DOI: 10.1002/mrc.2115

✦ Synopsis

Abstract

We present here a new method using methoxyphenylacetic acid (MPA) as the chiral derivatizing agent (CDA) for the assignment of absolute configuration of cyclic secondary amines. The MPA amides were prepared using the purification‐free ‘mix and shake’ method. A detailed conformational analysis for the two diastereomeric amides was conducted by 2D NMR experiments and molecular mechanics calculations. We have established that, in the most stable conformation of each syn rotamer of MPA amides, the H‐α in the MPA moiety is oriented toward the bulky substituent group at the asymmetric carbon in the chiral amine, presumably to avoid steric and/or electrostatic interactions. The observed NMR data were correlated with the conformational model to allow unambiguous assignment of absolute configuration of secondary amines. The results demonstrate that the MPA can be used as a useful CDA in the case of sterically crowded cyclic secondary amines from which the MTPA amides are usually difficult to make. Copyright © 2008 John Wiley & Sons, Ltd.