Issue 13, 2013

Readily accessible chiral at nitrogen cage structures

Abstract

The reaction of glycine-N-methyl amide with paraformaldehyde in the presence of ytterbium triflate (1 mol%) leads to a novel cage structure 6 which is chiral at nitrogen. Single crystal X-ray analysis and DFT calculations suggest this cage structure is rigid and adopts a single low energy conformation. Use of single enantiomer α-amino amides results in two diastereomeric tertiary amines that differ in their absolute configuration at nitrogen. These diastereoisomers interconvert under acidic conditions but are configurationally stable under basic conditions and can be readily separated by either crystallisation or column chromatography. By reacting racemic chiral α-amino amides a third diastereomeric cage can also be isolated through this reaction protocol. Preparation of mixed cages by reacting two different α-amino amides is also possible allowing for greater structural diversity in the products to be attained. Preliminary mechanistic studies show that all three methylene units in the cage structure are labile and can be replaced under acidic reaction conditions.

Graphical abstract: Readily accessible chiral at nitrogen cage structures

Supplementary files

Article information

Article type
Paper
Submitted
19 Dec 2012
Accepted
29 Jan 2013
First published
30 Jan 2013

Org. Biomol. Chem., 2013,11, 2198-2205

Readily accessible chiral at nitrogen cage structures

J. H. Rowley, S. C. Yau, B. M. Kariuki, A. R. Kennedy and N. C. O. Tomkinson, Org. Biomol. Chem., 2013, 11, 2198 DOI: 10.1039/C3OB27458F

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