Dynamic Covalent Chemistry Based On Imine And Iminium Ions

Dynamic covalent chemistry(DCC)is one of the cutting-edge areas in supramolecular chemistry nowadays.The reversible forming and breaking of covalent bonds and the thermodynamic controlled product distribution play an important role in constructing multi-functional supramolecular system.There are no doubts that explore the reversible covalent bond types associated with reaction mechanism can facilitate the rapid development of DCC.This article focus on Zn(OTf)2 templated dynamic covalent assemblies of 2-pyridinecarboxaldehyde,di(2-picolyl)amine,and primary aromatic amines/secondary aliphatic amines through imine/iminium pathway.Furthermore,we utilized in situ generated iminiun ions for the reversible binding and chirality discrimination of mono-alcohols.The main contents are as follows:1.Using piperidine as a model,the conditions of dynamic covalent reactions of 2-pyridinecarboxaldehyde,di(2-picoiyl)amine,secondary amines and Zn(OTf)2 were screened.1H-NMR and ESI-MS analysis shows that couteranion ligand in Bu4NX(X = Cl-?Br-?I-?AcO-)is necessary for forming aninal 1,and adding molecular sieves improve the yield.Two possible iminium pathways were revealed.The substrate scope of the mono-secondary amines was further expanded.Comparing with reaction yield and apparent equilibrium constant indicates that the nucleophilicity and steric effect of secondary amine have significant effects on the reaction.Finally,the resulting diastereomeric helical complexes were employed to determine enantiomeric excess of chiral secondary amines in conjunction with circular dichroism spectroscopy.2.Having explored the multi-component assembly with secondary amines,we next investigate the dynamic reaction with primary aromatic amines.Aldehydes and primary aromatic amines can easily form imines which are thermodynamically stable.The substituent groups of benzene could influence the C=N reactivity.A series of primary aromatic amines were employed to form aminal 3 and the equilibrium constant between imine and 3 were calculated.Analysis of the equilibrium constants using Hammett linear free energy relationships against ?+reveals that the substituent resonance effect are the major factor influenceing the reaction.The component exchange confired the reversibility of multi-component assembly.Kinetics experiment shows that two different pathways are involved and depending on the substitution groups on aromatic amines.3.The dynamic covalent binding of mono-alcohols through in situ generated iminiums from aromatic aldehyde and secondary amine were explored by 1H-NMR and ESI-MS.The apparent equilibrium constants of the multi-component reaction of aldehydes,secondary amines and alcohols were measured.The experiment data shows that the aldehyde with electron-withdrawing group can promote the reaction with higher efficiency,while the nucleophilicity and steric effect of secondary amine have significant effect on the reaction.The substrates which can participate in ?-? or polar-? interaction are able to stabilize the assembly,hence,moving the reaction toward the desired products.The reaction mechanism and the hemiaminal intermediates were investigated.To take advantage of high electrophilic affinity of imimiun,S-2-(methoxymethyl)pyrrolidine was exploited as chiral auxiliary,and chirality discrimination and ee measurement of chiral secondary alcohols were achieved.