Mechanism of Evolution of Koneramine Complexes from One‐Pot Reactions: Snapshots of Intermediates Offer Facile Routes to New Dipicolylamines

Abstract

Koneramines (L OR', R=Ph or Ts; R'=Me, iPr) and their complexes were found to emerge from the system of pyridine-2-carboxaldehyde and N-phenyl/tosylethylenediamine when a primary or secondary alcohol was used as solvent. Imidazolidinylpyridines (L , R=Ph or Ts) became major emergents whereas hemi-aminals (L OH, R=Ph or Ts) are minor emergents of the system when tertiary butanol was used as the solvent; the bulky tertiary butyl group prevented the addition of alcohol to the iminium ion that diverted the equilibrium towards imidazolidinylpyridines. By playing with the components of the reaction mixture, crystals of the metastable intermediates bound to copper(II) and/or zinc(II) were obtained and the structures were determined by X-ray diffraction analysis. The reported results shed light on how to control the emergents of the multicomponent reaction mixture that forms koneramines. Reactivity studies of the intermediates pave the way for a new type of koneramine complexes that are new dipicolylamines where the two pyridine moieties of the resulting koneramine are not the same.

Postsynthetic Modification Strengthens the Stereoselectively Self-Assembled Hemiaminal Ether Complexes

“…1). Furthermore we report the post-assembly modification of the fragile hemiaminal ether linkages 16 The formation of aforementioned complexes indicated that the HAE formation works in any primary and secondary alcohols and thiols except tertiary alcohols.…”

“…13 Our one-pot protocol allowed the stereoselective (syn or anti) and geometry specific (facial or meridional) assembly of hemiaminal ether ligands (L R OR') comprising 2,2'dipicolylamine backbone in good yield from prebiotically relevant multicomponent pool of mono-N-substituted ethylenediamines, pyridine-2-carboxaldehyde and primary alcohols or thiols at ambient conditions. [14][15][16][17] Although the multicomponent mixture contained both syn (RR and SS) and anti (RS and SR) forms of hemiaminal ether L R OR' is in dynamic equilibrium with plethora of other components such as hemiaminal and imidazoline, we succeeded to trap syn-L R OR' as complexes with Cu(II) and Zn(II) ions and anti-L R OR' by employing Ni(II) and Cd(II) ions.…”

Late‐stage Ligand Modification After Coordination Strengthens Stereoselectively Self‐Assembled Hemiaminal Ether Complexes

“…[5] Our one-pot protocol allowed the stereoselective (syn or anti) and geometry specific (facial or meridional) assembly of hemiaminal ether ligands (L R OR') comprising 2,2'-dipicolylamine backbone in good yield from prebiotically relevant multicomponent pool of mono-N-substituted ethylenediamines, pyridine-2-carboxaldehyde and primary alcohols or thiols at ambient conditions. [6][7][8][9] Although the multicomponent mixture contained both syn (RR and SS) and anti (RS and SR) forms of hemiaminal ether L R OR' in dynamic equilibrium with plethora of other components such as hemiaminal and imidazoline, we succeeded to trap syn-L R OR' as complexes with Cu(II) and Zn(II) ions and anti-L R OR' by employing Ni(II) and Cd(II) ions. Hemiaminal or hemiaminal ether moieties are known to be Achilles' heel and seldom isolated as part of cyclic compounds.…”

Investigating the photosensitivity of koneramines for cell imaging and therapeutic applications

“…Our group has recently reported a new family of potential tridentate ligands known as koneramines, [20][21][22] which contain a 2,2′-dipicolylamine scaffold. Initially, koneramines were stereoselectively self-assembled from a multicomponent onepot reaction of mono-N-substituted ethylenediamine and pyridine-2-carbinal in alcohol/thiol.…”