Readily accessible chiral at nitrogen cage structures

Julian Rowley, Sze Chak Yau, Benson M Kariuki, Alan Kennedy, Nick Tomkinson

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.
LanguageEnglish
Pages2198-2205
Number of pages8
JournalOrganic and Biomolecular Chemistry
Volume11
Issue number13
DOIs
Publication statusPublished - 6 Mar 2013

Fingerprint

Amides
amides
Nitrogen
nitrogen
Ytterbium
Sarcosine
Rigid structures
Enantiomers
enantiomers
X ray analysis
ytterbium
rigid structures
glycine
Crystallization
methylene
Discrete Fourier transforms
Amines
Conformations
amines
X-Rays

Keywords

  • nitrogen cage structures
  • paraformaldehyde
  • biomolecular chemistry

Cite this

Rowley, Julian ; Yau, Sze Chak ; Kariuki, Benson M ; Kennedy, Alan ; Tomkinson, Nick. / Readily accessible chiral at nitrogen cage structures. In: Organic and Biomolecular Chemistry. 2013 ; Vol. 11, No. 13. pp. 2198-2205 .
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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.",
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Readily accessible chiral at nitrogen cage structures. / Rowley, Julian; Yau, Sze Chak; Kariuki, Benson M; Kennedy, Alan; Tomkinson, Nick.

In: Organic and Biomolecular Chemistry, Vol. 11, No. 13, 06.03.2013, p. 2198-2205 .

Research output: Contribution to journalArticle

TY - JOUR

T1 - Readily accessible chiral at nitrogen cage structures

AU - Rowley, Julian

AU - Yau, Sze Chak

AU - Kariuki, Benson M

AU - Kennedy, Alan

AU - Tomkinson, Nick

PY - 2013/3/6

Y1 - 2013/3/6

N2 - 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.

AB - 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.

KW - nitrogen cage structures

KW - paraformaldehyde

KW - biomolecular chemistry

U2 - 10.1039/c3ob27458f

DO - 10.1039/c3ob27458f

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VL - 11

SP - 2198

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JO - Organic and Biomolecular Chemistry

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JF - Organic and Biomolecular Chemistry

SN - 1477-0520

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