[Dan]

Not a bad idea - the [2+2] cycloaddition looks like a good idea.

Problem is that KOH won't eliminate that alcohol - generally you need acid, but there are exceptions where an E1cb mechanism can operate (e.g. aldol condensation). The KOH will probably hydrolyse the nitrile to the carboxylate. The acid step might do the elimination you are looking for, though you might get a cationic rearrangement of the cyclobutane ring.

To simplify things, I would suggest a [2+2] cycloaddition of propadiene to acrylonitrile to give:

[Rutherford]

Yes, K is a hydrocarbon, so your proposition seems correct. KOH is used for converting -CN to -COO^- and H₃O⁺ is used to protonate the carboxylate anion. Thanks very much for the help.


I thought that I could do the rest alone, but I got stuck again, there are things I need to learn and I hope that I will do now. The new scheme is attached.
In the first step the keto group and the two carboxylate groups should be reduced, so I got a triol. What happens when TsCl in pyridine is added? That reaction blocks me.

[discodermolide]

TSCl/Py forms the para-toluenesulphonate ester of alcohols.
The tosylate thus formed is a good leaving group when attacked by nucleophiles.

[Rutherford]

I don't understand what will be the final product. A triol is made in the first step, so which -OH group takes part in the esterification?

[discodermolide]

Probably only the primary ones, but as no quantities of reagents are given I might assume all of them are tosylated?


By the way I am finding this thread very confusing!

[Rutherford]

Sorry, these are all parts from the same problem, so I thought to post them in the same topic. It was probably a bad idea. For the next scheme I will open a new topic.

I will continue with this one tomorrow. Thanks till now for the help.

[Dan]

Yes, K is a hydrocarbon, so your proposition seems correct.

It would help if you share these additional bits of information from the beginning, do you have any other such hints?

I thought I had it up to U, but I can't see what the hydroxylamine will do, so maybe not...

[Rutherford]

There is no additional info for this scheme and I can't get further than Q  .

[discodermolide]

I said this already, R are the tosylates, two primary and one secondary.
Tosylates, which are good leaving groups. They then react with the malonate ester, presumably under basic conditions. So look at that and see where you get.
tri tosylate

di tosylate(s)
and

mono tosylate


or less likely

[Rutherford]

I assumed that the keto group didn't get reduced, so I ended with V being the compound attached. What happens then in the last reactions, if the compound is acceptable?

[discodermolide]

Why should the ketone not be reduced by LAH?

OK let's assume it didn't, that is not a reasonable product. The step that is false is T :rarrow:U.
In this case T is this compound
So how does an acid react with SOCl2 then NaN3, heat in the presence of tButanol, a named reaction by the way.

[Rutherford]

I thought that an acyl chloride was made, afterwards I didn't know . What is the role of the azide and tbutanol?

[discodermolide]

Right you get an acid chloride. NaN₃ acts as a nucleophile and does what? Don't forget the heat.

[Rutherford]

Substitution so I got the chlorine replaced by azide ion. Don't know what happens then.

[discodermolide]

OK, it's a Curtius rearrangement. See the picture. So now we know U (The compounds in brackets are not isolated).