My understanding is that aza-enolates have an advantage over enamines in enolate-type alkylations because the reaction at N is less likely. As a result, unactivated electrophiles can be used (i.e. electrophiles that are not allylic / benzylic / $\alpha$-halo, source: Clayden et al., p. 593)

Question: why is the lone pair on N in aza-enolates less reactive?

  • 4
    $\begingroup$ From how I understand it, the problem with enamines + unactivated electrophiles is self-condensation. This naturally prevented in the N-enolate. $\endgroup$ Oct 15 '17 at 13:46
  • $\begingroup$ @deus ex machina So would you say that the raction at N isn't a problem at all? Why? $\endgroup$ Oct 28 '17 at 10:06
  • $\begingroup$ Because the n-enolate prevents an electrophilic site $\endgroup$ Oct 28 '17 at 10:58
  • $\begingroup$ @deusexmachina No I mean, the enolate / enamine acting as a nucleophile at N. Because although the carbon will be the soft nucleophilic centre, the electron density on N will be greater, so why won't "harder" electrophiles react with it? $\endgroup$ Oct 28 '17 at 11:02
  • $\begingroup$ @deusexmachina From Clayden, Ed. 2, p. 592: "There is, however, a major problem with enamines: reaction at nitrogen. Less reactive alkylating agents -- simple alkyl halides such as methyl iodide, for example -- react to a significant degree at N rather at C. The product is a quaternary ammonium salt, which hydrolyses back to the starting material and leads to low yields". $\endgroup$ Oct 28 '17 at 11:04

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