[Pranav]

I have attached the question. Ignore the marks made with the pen.

I was able to correctly answer the first question but my answer of second is marked incorrect. For second, I started with considering the chiral centres. I found two carbons and one nitrogen to be chiral. This makes a total of 6 stereoisomers but the answer key states its 4. I am fully aware of pyramidal inversion. If we consider that pyramidal inversion makes it impossible to resolve the stereoisomers, the answer is 4. Can someone please help me on this? Should I not consider nitrogen a chiral centre while solving questions?

[betterbesafehero]

Your answer is in your last question

[Dan]

1. If you consider you have 3 stereogenic centres, you will have 2³ = 8 stereoisomers. I do not see 6 as a logical answer in any case.

2. It is almost always the case that amines will undergo rapid pyramidal inversion and should not be considered stereogenic. Aziridines, azetidines and other N centres with unusually high energy barriers to pyramidal inversion may be resolvable. However, pyramidal inversion is not relevant here because...

3. We are not dealing with an amine here, it is an amide. The N is planar (sp²). Restricted C(O)-N bond rotation could result in E/Z isomerism, but as far as I am aware E/Z isomers of amides interconvert too readily to be separated. There are only two stereogenic centres.

[betterbesafehero]

and I would assume that someone has got a very propitious answer just because of me

[betterbesafehero]

1. If you consider you have 3 stereogenic centres, you will have 2³ = 8 stereoisomers. I do not see 6 as a logical answer in any case.

I too thought that, time to do some maths

[Pranav]

1. If you consider you have 3 stereogenic centres, you will have 2³ = 8 stereoisomers. I do not see 6 as a logical answer in any case.

Ah yes, you are right. I think I did it hastily during the examination and the 6 remained in my head.

2. It is almost always the case that amines will undergo rapid pyramidal inversion and should not be considered stereogenic. Aziridines, azetidines and other N centres with unusually high energy barriers to pyramidal inversion may be resolvable.

I do have a slight idea about it but they aren't usually asked in my exams and they aren't even in my syllabus too. 

However, pyramidal inversion is not relevant here because...

3. We are not dealing with an amine here, it is an amide. The N is planar (sp²). Restricted C(O)-N bond rotation could result in E/Z isomerism, but as far as I am aware E/Z isomers of amides interconvert too readily to be separated. There are only two stereogenic centres.

Thank you Dan! That is a nice explanation, thanks!

[AWK]

http://www.rod.beavon.clara.net/chiralit.htm
http://en.wikipedia.org/wiki/Tr%C3%B6ger%27s_base

[Pranav]

Thanks AWK!

I still have one question. What if it was an amine instead of amide? Should the answer be 8 or 4?

[AWK]

Amide group is flat - no stereogenic center

[Pranav]

Amide group is flat - no stereogenic center

I understand that but what if there was an amine in the question? Should the answer be 8 or 4? Because theoretically, we can say that amine is a chiral centre but due to pyramidal inversion, it is not resolvable, does that mean I should restrict my answer to 4?

[iamback]

Amide group is flat - no stereogenic center

I understand that but what if there was an amine in the question? Should the answer be 8 or 4? Because theoretically, we can say that amine is a chiral centre but due to pyramidal inversion, it is not resolvable, does that mean I should restrict my answer to 4?

You are right pranav

[AWK]

Amine Nitrogen (no hydrogen atom at N) is stereogenic only when involved in rings (mainly  3-membered). Even more steric hindrance should cooperate.
Note - nitrogen atom of quinine is stereogenic (inversion is impossible) though textbooks did not inform about it.

[Pranav]

Amine Nitrogen (no hydrogen atom at N) is stereogenic only when involved in rings (mainly  3-membered). Even more steric hindrance should cooperate.
Note - nitrogen atom of quinine is stereogenic (inversion is impossible) though textbooks did not inform about it.

Thank you AWK!