Imines mechanistic considerations

The cycloaddition of diazomethane to SchifT bases from heterocyclic aldehydes and anilines provides a useful route to heterocyclic substituted triazolines. Unlike olefins bearing heterocyclic substituents, the heterocyclic imines can be obtained readily by reaction of the appropriate aldehyde and amine thus the diazomethane-imine addition has greater scope than the olefin-azide reaction. NMR spectroscopic studies of the orientation of addition are in accord with previously reported mechanistic considerations (see, e.g., Scheme 93).329 In addition to the influence of the N-aryl group, the electron-withdrawing power of the heterocyclic substituent on the Schiff-base carbon also has a substantial effect on imine reactivity, in the order 2-quinolyl 2-, 3-, or 4-pyridyl > phenyl > 2-thienyl as 2-furyl.329... 

Treatment of amino acid 156, imine and 2-chloro-l-methylpyridinium iodide (Mukaiyama s reagent) in the presence of triethylamine in refluxing dichloro-methane afforded spiro-(3-lactams 157,158. These were obtained as a 1.8 1 mixture of diastereoisomers and separated by column chromatography. The reaction of 159 and imine under the usual experimental conditions resulted in the formation of a single diastereoisomer 160. The absolute (3 S, 4 S, 7 -configuration was assigned on the basis of mechanistic considerations and XH NMR spectra. The presence of the stereocenter affords complete diastereoselectivity (only trans diastereoisomers 157, 158) and enantioselectivity (160). 

Scheme 5.2.40 Mechanistic considerations for reactions of E/Z-2-butenylstannanes with imines...

The mechanistic considerations are based mainly on the fact that amino nitriles 29 and 29 rapidly equilibrate in alkaline solution through the intermediacy of imine 28 but not in acid solution. The Read reaction is conducted under acidic conditions so that the interconversion of 29 to (29) is... 

It is assumed that both reactions start with the formation of the imine of the acyclic structure of carbohydrates with proline. After this initial step, the cyanoacetate 86 dictates aKnoevenagel/Michael cascade, whereas by employment of isocyanoacetate 87 a nucleophilic addition of the carbon atom of the isocyano group and subsequent rearrangement reaction are observed. An explanation for this different behavior of the isostructural compounds (ethyl esters 86 and 87) depicted in Scheme 2.18 is given by the different sites of highest nucleophilicity as described by Mayr et al. [41]. These mechanistic considerations are depicted in Scheme 2.19. 

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