Metal ions as external stimuli in stereoselective self-sorting of koneramines and thiokoneramines

Abstract

Stereoselective self-sorting of koneramines and thiokoneramines, which are N3 ligands, evolved from the system of pyridine-2-carboxaldehyde, mono-N-substituted ethylenediamine, primary alcohol or thiol, is observed when metal ions such as Ni(ii), Cu(ii), Zn(ii) and Cd(ii) are added as external stimuli to isolate the emergent molecule.

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

“…The initial characterization of the reaction mixture by using electrospray ionization mass spectrometry exhibited the presence of [Cu(L Ph O i Pr)Cl] + monocations as the most abundant species (observed m / z =472.1055, Figure S1 in the Supporting Information; calculated m / z =472.1091, Figure S2 in the Supporting Information), which suggested the formation of [Cu(L Ph O i Pr)Cl 2 ]. As none of the efforts in crystallizing [Cu(L Ph O i Pr)Cl 2 ] were fruitful, the chloride anions were exchanged to tosylate by using two equivalents of AgOTs (Figures S3, S4 in the Supporting Information); single‐crystal X‐ray diffraction analysis (SCXRD) revealed the structure as syn ‐[Cu(L Ph O i Pr)(OTs) 2 (H 2 O)], which was expected . Previous reactions towards Cu‐koneramines also always selectively yielded racemic mixtures of syn (6 R ,7 R and 6 S ,7 S ) forms (Figure ); anti (6 R ,7 S and 6 S ,7 R ) forms of Cu‐koneramines have never been observed .…”

“…The koneramine complexes syn ‐[Cu(L Ph OMe)Cl 2 ], syn ‐[Zn(L Ph OMe)Cl 2 ], anti ‐[Ni(L Ph OMe)(H 2 O)Cl 2 ], and anti ‐[Cd(L Ph OMe)(μ‐Cl)Cl] 2 were isolated when methanol was used as the solvent, where methanol easily attacked the iminium ion 10 . We have equilibrated a mixture of an equivalent of N ‐phenylethylenediamine and two equivalents of pyridine‐2‐carboxaldehyde in isopropanol (Scheme ) . The Cu‐koneramine complex formation at the conditions reported by us recently was performed by adding an equivalent of copper(II) salt as an isopropanol solution .…”

“…Our group recently reported a protocol involving multiple components forming complexes of koneramines . We have also reported the stereoselective self‐sorting of koneramines and thiokoneramines by using transition metal ions as external stimuli (Ni 2+ , Cu 2+ , Zn 2+ , Cd 2+ ) . The Cu II ions coordinate with syn forms of koneramines specifically in equatorial fashion; Ni II and Cd II ions facially coordinate with anti ‐koneramines specifically .…”

“…However Zn II complexes of facially bound anti ‐koneramines were isolated at low temperature in low yields . On the other hand, only anti ‐thiokoneramines are known to coordinate to transition metal ions (Ni 2+ , Cu 2+ , Zn 2+ , Cd 2+ ) in equatorial fashion; complexes of syn ‐thiokoneramines have not been isolated yet . This emergent phenomenon where transition metal ions serve as irreversible external stimuli has been interesting and is a less explored avenue in the literature …”

“…We have hypothesized that the multicomponent system recently reported by us (Scheme ) produces 2‐(1‐phenylimidazolidin‐2‐yl)pyridine (6 ) as the first checkpoint, which eventually yields the next checkpoint (3‐phenyl‐2‐(pyridin‐2‐yl)imidazolidin‐1‐yl)(pyridin‐2‐yl)methanol ( 8 ); this hemi‐aminal ( 8 ) ultimately delivers the strategic component of the system—3‐phenyl‐2‐(pyridin‐2‐yl)‐1‐(pyridin‐2‐ylmethylene)imidazolidin‐1‐ium cation ( 10 )—which could be attacked by nucleophilic solvent molecules such as alcohols to yield the 2‐(methoxy(3‐phenyl‐2‐(pyridin‐2‐yl)imidazolidin‐1‐yl)methyl)pyridine ( 12 ), a hemi‐aminal ether called a koneramine (R=Ph; R′=Me) . In this paper, we provide unequivocal support for the proposed intermediacy of metastable imidazolidine ( 6 ), hemi‐aminal ( 8 ), and iminium ion ( 10 ) in the formation of koneramines ( 12 ) by tweaking the multicomponent system to divert the equilibrium towards a different emergent.…”