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Chemistry Forums for Students => Organic Chemistry Forum => Topic started by: xshadow on June 05, 2021, 07:43:34 AM

Title: Retrosynthetic analysis ecercise
Post by: xshadow on June 05, 2021, 07:43:34 AM
I'm stuck in the last step(I hope) of this retrosynthesis:
(https://i.imgur.com/KTh2lbH.jpg)

There will be another cyclization but I don't know how get that

In order to get another cyclopentane I need that C1 attaccks C5 ...but how?!!

Before that I  think that the OH- group leaves and I get an aldol condensation
I don't know how closing that ring with an alkene + an α-β unsaturated ketone as main funcitiona l group

PS: I miss  the first stage where  I oxidize the alcohol using PCC


Thanks


Title: Re: Retrosynthetic analysis ecercise
Post by: xshadow on June 10, 2021, 05:29:43 PM
Update:  I found this possible solution
(https://i.imgur.com/ezSj6mY.jpg)

May have it sense?
Thanks :)
Title: Re: Retrosynthetic analysis ecercise
Post by: rolnor on June 11, 2021, 07:47:58 AM
It looks messy. H2/PdC will hydrogenate the bromide. This is not a simple exercise!
Title: Re: Retrosynthetic analysis ecercise
Post by: Meter on June 11, 2021, 07:54:05 AM
Quote from: rolnor on June 11, 2021, 07:47:58 AM
It looks messy. H2/PdC will hydrogenate the bromide. This is not a simple exercise!
I haven't heard of this. H2/Pd/C can be used to substitute halide moieties with hydrogen?

Title: Re: Retrosynthetic analysis ecercise
Post by: rolnor on June 11, 2021, 09:32:56 AM
Yes. Also the ketone carbonyl close to the bromide can also form anion and attack the bromide. Also this carbonyl anion can attack the other carbonyl so you get the wrong product.
Title: Re: Retrosynthetic analysis ecercise
Post by: Meter on June 11, 2021, 10:46:21 AM
Never realized it was that simple. Always thought you had to use some sort of hydride donor (I have seen NaBH4 used in some sources?) like NaH.
Title: Re: Retrosynthetic analysis ecercise
Post by: rolnor on June 11, 2021, 10:57:38 AM
NaH is no good, strong base, very bad nucleophile. LiAlEt3H is better.
Title: Re: Retrosynthetic analysis ecercise
Post by: Meter on June 11, 2021, 11:33:48 AM
Ah, of course. In practice, is catalytic hydrogenation generally used for this purpose, or are reagents preferred?
Title: Re: Retrosynthetic analysis ecercise
Post by: rolnor on June 11, 2021, 12:59:25 PM
You dont often want to do this reaction really, its more a side-reaction in my experience.
Title: Re: Retrosynthetic analysis ecercise
Post by: rolnor on June 11, 2021, 01:06:06 PM
I checked now am maybe I am mistaking, aryl halides are often hydrogenated but I dont find alkylhalides. Its very possible you can do it but Iam not sure anymore.
Title: Re: Retrosynthetic analysis ecercise
Post by: Meter on June 11, 2021, 01:13:52 PM
I suppose a way to selectively hydrogenate bromide groups is to make a Grignard reagent and then treat it with an excess of water.
Title: Re: Retrosynthetic analysis ecercise
Post by: rolnor on June 11, 2021, 03:46:29 PM
Yes, I have seen you can do it with Mg/propanol in one step. I also checked, the best reagent to use is LiBEt3H, this is a very powerfull Sn2-nucleophile.
Title: Re: Retrosynthetic analysis ecercise
Post by: kriggy on June 16, 2021, 05:37:32 AM
Quote from: rolnor on June 11, 2021, 12:59:25 PM
You dont often want to do this reaction really, its more a side-reaction in my experience.

Nah, we do it all the time in our lab using D2 or T2 gas to introduce isotope labels but yeah 99% its just pain in the ass side reaction. It can be solved by use of other hydrogenation catalysts than Pd/C.
Title: Re: Retrosynthetic analysis ecercise
Post by: rolnor on June 16, 2021, 06:40:04 AM
Great! The reaction is not described in Marchs Adv. Org. Chem. so I became unsure about it.