Chemical Forums
Chemistry Forums for Students => Organic Chemistry Forum => Topic started by: John Mcmurry on August 14, 2018, 08:03:44 AM
-
Hello!
Could anybody help me out finding the reagents for a succesful synthesis starting with cyclopent-4-ene-1,3-dione and ending with spiro[4.4]non-2-ene? I am totally lost on that one.
Thanks...
-
It is a forum rule that you must at least show that you've attempted the problem.
Have you had any instruction on retrosynthesis?
-
Nope...
-
Basically, it involves working backward from the product one step at a time. Let's see what you can come up with...
-
The dione has very acidic hydrogens and would form a good nucleophile if base were added but it is also a excellent Michael-type alpha-beta unsaturated molecule and would probably polymerase very quickly under basic conditions, its a tricky startingmaterial.
-
I would start by numbering atoms in the starting material and products, to identify where you need to make and break bonds.
-
I can't find any mechanism that makes sense in this case
-
I can't even find a way to remove the two C=O bonds. Maybe reduce them to C-OH, but what then?
-
Reducing the C=O by grignard to C-OH
-
There are many ways of reducing a ketone to an alkane. In fact if you type "ketone to alkane" into google the easiest way is the first result.
However, I suggest that this reduction not be your first step. You have a highly activated spot between the two carbonyls, what type of chemistry could you do there?
-
Wolff-Kishner Reduction, my bad!
Between the two carbonyls, maybe NBS and hr, inserting an Br. Then making an diorganocopper reaction with my R'-Br and the cyclopentane-CuLi?
-
Then I got this? Can I then reduce the two C=O with W-K reduction? and the synthesis is done
-
Something like this?
-
Very good, and very close. Take a look again at your cuprate. Its a bit off.
-
But I just realized that I would end with this, right?
-
How do I create the cyclopentane without that "extra" bond? I have to use a butane with some kind of terminal groups, right?
-
I would consider reversing the polarities of the two pieces that you are trying to bring together.
-
Oops, I didnt look closely enough. The cuprate route isn't the way to go.
I agree with using butane with 2 terminal groups. Babcock is on the track I was originally thinking. What is another type of chemistry that a methylene alpha to a carbonyl can do? And two carbonyls even better.
-
I think if you mix this enone with base you will get dimer or polymer, Michael-addition. Also if you try to remove the carbonyls with Woolf-Kischner you will have attack by hydrazine on the double-bond.
-
That makes this quite a difficult substrate rolnor.
-
Perhaps self condensation (polymerization) could be minimized by the appropriate choice of addition of reagents, but I don't have direct knowledge. I also wonder whether or not a plausible route, especially if possible side reactions are acknowledged, might be good enough for the purposes of this problem.
-
How about protection of the double bond - e.g. with Br2 which you may be able to reduce back off with zinc, or as the epoxide (and then removal with PPh3?)
Just some random thoughts
-
I'm kicking myself sjb, because I had the exact same two thoughts (bromination or epoxidation), then discarded them because I couldnt think of how to to "deprotect" the double bond correctly.
-
Hah, I was just looking through some old notes earlier and thought of the thread :) Not sure about the epoxidation route now I think it through, it is more used to invert the ene geometry so I don't think will be effective here.
-
If you react an epoxide with LAH you'll get an alcohol, which can be dehydrated with a strong acid. That's a nice route.
https://pubs.acs.org/doi/pdf/10.1021/ja01038a042
-
I think the epoxide can be converted back to alkene with PPh3 but epoxides are also electrophiles and can react if base is added.