title: Probing the mechanism and dynamic reversibility of trianglimine formation using real-time electrospray ionization time-of-flight mass spectrometry.
abstract: BACKGROUND
  The [3+3]-cyclocondensation reactions of chiral (1R,2R)-1,2-diaminocyclohexane with aromatic or aliphatic bis-aldehydes to form trianglimine macrocycles were reported a decade ago and were believed to proceed through a stepwise mechanistic pathway; however, no intermediates were ever isolated or detected and characterized.
  
  
  METHODS
  We investigated the mechanism of the [3+3]-cyclocondensation reaction using a selection of dialdehyde starting materials using real-time electrospray ionization time-of-flight mass spectrometry.
  
  
  RESULTS
  We observed up to a maximum of 16 reaction intermediates along the reaction pathway, more than for any other multistep reaction reported. We also probed the dynamic reversibility of trianglimines using selected small dynamic combinatorial libraries and showed that trianglimine formation is indeed fully reversible.
  
  
  CONCLUSIONS
  This study represents a significant contribution towards understanding the mechanism of trianglimine formation and its potential applicability can be extended to include other cascade reactions.
authors.affiliation: School of Engineering and Science, Organic and Analytical Chemistry Laboratory, Jacobs University, 28759, Bremen, Germany.
authors.forename: Hany F
authors.initials: HF
authors.lastname: Nour
authors.forename: Ana M
authors.initials: AM
authors.lastname: Lopez-Periago
authors.forename: Nikolai
authors.initials: N
authors.lastname: Kuhnert
mesh_terms: D000447:Aldehydes / Q000737:chemistry; D003500:Cyclization; D007477:Ions / Q000737:chemistry; D047028:Macrocyclic Compounds / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D000447:Aldehydes; D007477:Ions; D047028:Macrocyclic Compounds; C511280:trianglimine