Retrosynthesis help

[ivanos]

Hello,

I have a problem with retrosynthesis as shown on Fig. 1. I have to synthesize the product starting from cyclohexenone. I think first step in normal synthesis will be the Michael addition as shown on Fig. 2., but I have no idea about next steps. Do you have any advice?

[hypervalent_iodine]

I wouldn't do the 1,4 addition first. You'll notice that your other group if attached to the alpha carbon. If you've learned about Michael additions, I assume you know about the special reactivity that those centres impart? If you do the Michael addition first, you open up not only the alpha carbon you want to react, but the other one as well. Think about reactions you know that use the alpha carbon for creating C-C bonds. That should help you.

[ivanos]

I thought I could do LDA/2-iodopropane as a next step (through enolate form), but now I am confused.

[hypervalent_iodine]

The problem is that you have three potential products because you have two alpha carbons in that compound. You could end up alkylating one or both of those, and good luck trying to separate them out (I realise this probably isn't something you're doing, but it's worth taking into consideration). I would alkylate with your method at the alpha position first, then do the Michael.

[ivanos]

Thank you for help! Now it's clear. Here is a proposed synthetic route which I made. Is it correct to use TMS group in β-elimination to form the final α,β-unsaturated carbonyl? The problem is that my starting material will be 5-(trimethylsilyl)cyclohex-2-enone which isn't commercially available. I know that this compound could be synthesized from anisole but doesn't make it whole synthesis too complicated?

I thought about using NBS to perform β-elimination, but the problem is the double bond in side chain. Do you have any other ideas about formation of α,β-unsaturated fragment?