Regioselectivity of Deprotonation of Imines by Hindered Amide Bases
Smith, Jon Kirk
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Studies by a number of groups have suggested that deprotonation of carbonyl compounds and their derivatives generally occurs anti to the lone pair of the C=N nitrogen. This is accounted for in terms of electronic effects, chelation and syn anion stabilization through homoaromaticity. Contrary to the predictive generalizations, Bergbreiter and Newcomb have shown that Oimethylhydrazones COMH), prepared from 3-pentanone deprotonate with low regioselectivity when deprotonation is accomplished wi,th the hindered amide base, Lithium Diisopropylamide (LDA). They suspected that steric effects as well as electronic effects determined the position of deprotonation in otherwise electronically equivalent acidic protons. In light of Bergbreiter's results, and the close similairity between imines and DMHs, the cumulative effects of steric and electronic factors were examined in the deprotonation of various imines by hindered amide bases. In this study, it was found that deprotonation of tert-butylimine pre ared from 2-butanone by LOA had low regioselectivity. In addition, steric effects were more contributory in the kinetic deproton~ ation, and that electronic effects were more contributory in the thermodynamic deprotonation of the tert-butylimine. Experiments showed that for the deprotonation of 2-butanone tert-butylimine by LDA, the base was zero order in the rate equation, and the mechanism proposed suggests that isomerization about the C=N bond prior to deprotonation is the rate determining step, scheme.