[johnnyd]

I was unsure how to title this thread.

My issue is this: I am attempting to carry out an assymtric reduction on a ketone that is highly symmetrical. As such, the ee observed is poor. I would like to try to increase the selectivity by increasing the steric bulk around an aromatic nitro group in my compound (and so increase the "desymmetry"?).

So what I would ideally like, is a protect and deprotect strategy for an aromatic nitro group. I don't think one exists myself but please please please prove me wrong. the larger the steric influence that this group can have the better? Obviously, I'm looking to add only 2 steps to my synthesis - ie not go down to amine and back up.

For instance, is there any way to react at the oxygen? And then cleave? I realise that I'm reaching here...

[Åke]

I was unsure how to title this thread.

How about: Enantioselective reduction of a ketone

Anyway, the desired product can be obtained in one simple step by employing Corey-Itsuno (a.k.a. CBS) reduction, for more information check:

1. http://en.wikipedia.org/wiki/Corey-Itsuno_reduction
2. http://www.organic-chemistry.org/namedreactions/corey-bakshi-shibata-reduction.shtm

[willug]

I think you might have missed the point there Ake...

[Åke]

OK, so what was the point? 

[fledarmus]

OK, so what was the point? 

My guess was that he already has an assymetric reduction, probably the one you refer to. Unfortunately, the steric difference between the two substituents is not large enough to get good selectivity, and he wonders whether there is a simple way to make a nitro group much larger to drive the selectivity, without adding more than two steps (equivalent to protection/deprotection) to the synthetic sequence.

[Honclbrif]

I've never seen anything amounting to a "protection" of a nitro group. Quick scan of Greene isn't revealing anything either.

You can reduce it to an amino and put a big bulky protecting group on, react, deprotect, and take it back up to the nitro. But as I understand it, amine to nitro is a pretty obnoxious transformation. Unless your goal is to end with an amino anyway, in which case, just change the order you do things in. May require protection of the ketone first, then reduction/protection of the nitrogen. Honestly, I don't know if you'll get out of this one without a few more transformations then you want.

[Åke]

fledarmus, you're probably right. Among factors which influence the ee are the reaction temperature as well as the B-alkyl substituent of the CBS catalyst - it remains unknown if this has been considered.

[johnnyd]

Thanks guys. Fledarmus has described the problem very nicely. I suspected that the amine route might be the only way alright but thought it was worth asking. Thanks.

[Åke]

But did you try fine-tuning the CBS catalyst? I’d try that before modifying the substrate. Spur et al. obtianed low ee during their reduction of a ketone using the CBS method. However, by switching from B-methyl to B-n-butyl CBS catalyst, adding catecholborane extremely slowly and conducting the reduction at low temperature they were able to increase the ee substantially.¹

1. Rodriguez, A., Nomen, M., Spur, B. W., Godfroid, J.-J. An efficient asymmetric synthesis of prostaglandin E₁. Eur. J. Org. Chem. 1999, 2655-2662 http://onlinelibrary.wiley.com/doi/10.1002/%28SICI%291099-0690%28199910%291999:10%3C2655::AID-EJOC2655%3E3.0.CO;2-2/abstract

[g-bones]

I am trying to picture what you are saying but it would be easier just to see what your substrate looks like.