Under what circumstances can the stereochemistry at nitrogen atom be faithfully retained and identified?

Because in most cases nitrogen atoms tend to undergo stereorandomisation by flipping due to its lone pair. I know of one example which has a three membered ring where nitrogen flips very slowly due to the high s character in the lone pair which requires significant activation energy to flip. But I wanted to know of the other cases where this is possible (probably in a stereo locked system inhibiting flipping).

  • 1
    $\begingroup$ Kill that lone pair, and the problem will be gone. I believe tetraalkylammonium cations don't flip. $\endgroup$ May 14 '18 at 17:17
  • $\begingroup$ The TS for nitrogen inversion involves the lone pair being in a p orbital. Putting more s character in the orbital holding the lone pair moves it further away from the TS and increases the inversion barrier. Electronegative substituents will have this effect (Bent's Rule) on the lone pair orbital. $\ce{NF3}$ has a calculated inversion barrier of 78.5 kcal/m $\endgroup$
    – ron
    May 14 '18 at 18:48

You could try to lock the conformation of structure. For example, derivatives of a 1-azabicyclo[2.2.2]octane system could have a chiral nitrogen, and the fact that the substituents are tied back prevents inversion of the nitrogen. Quinine has this kind of structural moiety.

This example isn't exactly what you're looking for, but it does it by using diastereocontrol to limit the amount of undesired isomer: J. Org. Chem. 2004, 69 (3), 714–718.

As Ivan suggested, you can hold onto the lone pair with something. Here's an example where metal coordination prevents inversion: Inorg. Chem. 2012, 51 (15), 8516–8523.

There are plenty of others. I just did a quick search on the JACS website for stereogenic nitrogen.


Your Answer

By clicking “Post Your Answer”, you agree to our terms of service, privacy policy and cookie policy

Not the answer you're looking for? Browse other questions tagged or ask your own question.