Isomerization of imines

In addition to cydocondensation reactions of the Paal-Knorr type, cycloaddition processes play a prominent role in the construction of pyrrole rings. Thus, 1,3-dipo-lar cycloadditions of azomethine ylides with alkene dipolarophiles are very important in the preparation of pyrroles. The group of de la Hoz has studied the micro-wave-induced thermal isomerization of imines, derived from a-aminoesters, to azomethine ylides (Scheme 6.185) [346]. In the presence of equimolar amounts of /i-nitrostyrenes, three isomeric pyrrolidines (nitroproline esters) were obtained under solvent-free conditions in 81-86% yield within 10-15 min at 110-120 °C through a [3+2] cycloaddition process. Interestingly, using classical heating in an oil bath (toluene reflux, 24 h), only two of the three isomers were observed. 

Nitrile oxides are often generated by the dehydration of nitro compounds by reagents such as phenyl isocyanate. Azomethine ylides can be generated by the pyrolysis of aziridines or by the prototopic isomerization of imines upon heating. 

More recently, we have found that the role of the isomerization pathways in the reaction between ketenes and imines can be extended to the (E)/(Z) isomerization of imines themselves [68]. Thus, the stereocontrol observed in the reaction between methoxyketene 41 and (E)-imines (62a,b) was attributed to the competition between the energy barriers associated with the formation of intermediates (63a,b) and (65a,b) and the energies of activation corresponding to the isomerisation of (E)-imines (62a,b). Inclusion of isomerisation processes involving both imines (62a,b) and zwitterionic intermediates (63a,b) and (65a,b) led to a more complex kinetic analysis. As the final steps leading to (3-lactams (64) can be considered irreversible, the formation of both cis- and trans-(64) can be described by (3) and (4) ... 

Diiminothietane undergoes isomerization according to Equation (1). The free energy of activation of this process (AG = 74.0 kj mol-1) lies in the range of typical activation barriers for (E)/(Z)-isomerization of imines <1999CC2439>. 

On the basis of the high. 4-factors, low activation energies, and relative insensitivity of rates with respect to solvents and substituents, Talaty and Fargo consider a linear transition state in which one or both nitrogen atoms acquire an sp hybrid state, as the most likely one for the isomerization reaction. A similar transition state has been postulated for the cis - trans isomerization of imines and di-fluorodiimide. ... 

Scheme 28 Transition structures (112a-d) corresponding to the degenerate isomerization of imines (108a-d)...

In addition, our computational study revealed that the origin of this surprising behavior relies on the relative rates associated with the ( ) (Z) isomerization of imines lla,b and with the nucleophilic attack on methoxyketene 7b. The... 

FIGURE 2,6 Fully optimized structures of the transition structures associated with the (E) —> (Z) isomerization of imines ( )-la,b at B3LYP(PCM)/6-31+G //B3LYP(PCM)/6-31G +AZPVE level of theory. Bond distances and angles are given in angstrom and degrees, respectively. Reproduced from Ref. [91] with permission. 

Hayashi, et al. developed an enantioselective formal aza [3+3] cycloaddition of a,p-unsaturated aldehydes and enamide (enecarbamate) providing tetrahydropyil-din-2-ol in excellent enantioselectivities and yield. Scheme 3.50 [66]. The reaction comprised four consecutive reactions ene reaction, isomerization of imine to enecarbamate, hydrolysis and hemiacetal formation. Noteworthy, examples of a,P-unsaturated aldehydes acting as enophile in intermolecular catalytic enantioselective ene reaction are rare, and the reaction developed by Hayashi represents one of the successful example in such category. 

The photochemical ,Z-isomerization of imines carrying alkyl, aryl, or acyl substituents at the nitrogen of their CN group, on the other hand, was reported much later. This was due to the fact that the energy... 

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