[quantumnumber]

Hi guys,

I was trying to solve a retrosynthetic analysis excersice and I think I can't do what a I first thought. Here I attach the route I've followed. The point is... Is it possible to create the synthon "A"? Could I somehow make an enolate equivalent of that kind with an enone?

Thanks a lot!

[clarkstill]

That is an entirely reasonable synthon: it is the enolate product of deprotonation at the kinetic position, using a strong base such as LDA. In practice, however, you might run into problems with side reactions, such as the enolate adding directly to the ketone, rather than going 1,4.  In practice, you can solve this problem by position an ester attached to 'A' at the position where the anion is formed.  The beta keto ester enolate is much more stable, allowing you to use a weaker base.  The anion is also softer, and so adds 1,4 rather than 1,2.  Then you can just hydrolyse and decarboxylate the ester to remove it when it's no longer needed.

[quantumnumber]

That is an entirely reasonable synthon: it is the enolate product of deprotonation at the kinetic position, using a strong base such as LDA. In practice, however, you might run into problems with side reactions, such as the enolate adding directly to the ketone, rather than going 1,4.  In practice, you can solve this problem by position an ester attached to 'A' at the position where the anion is formed.  The beta keto ester enolate is much more stable, allowing you to use a weaker base.  The anion is also softer, and so adds 1,4 rather than 1,2.  Then you can just hydrolyse and decarboxylate the ester to remove it when it's no longer needed.

Thanks a lot for your response. It was just I think I never saw an enone-enolate equivalent... I dindn't know if there could be any problem in making them.

What about making the lithium enolate with LDA, and then the sylil enol eter? This would be a softer enolate equivalent too...

[clarkstill]

Yeah the Sakurai reaction with the silyl enol ether might help, or you could try enamine catalysis a la Hajos-Parrish.

[orgopete]

That is an entirely reasonable synthon: it is the enolate product of deprotonation at the kinetic position, using a strong base such as LDA. In practice, however, you might run into problems with side reactions, such as the enolate adding directly to the ketone, rather than going 1,4.  In practice, you can solve this problem by position an ester attached to 'A' at the position where the anion is formed.  The beta keto ester enolate is much more stable, allowing you to use a weaker base.  The anion is also softer, and so adds 1,4 rather than 1,2.  Then you can just hydrolyse and decarboxylate the ester to remove it when it's no longer needed.

I agree with this suggestion. This is how I had rationalized these reactions. I argued the kinetic products are the 1,2-addition reactions. If the retro addition gives a weaker base, then it can revert. In this case, the alkoxide would give a beta-ketoester enolate, a weaker base then the alkoxide. If it were to give a conjugate addition, this will give an enolate of the ketone. Protonation will now remain as the ketone is now at an even lower acidity. I reason that conjugate addition nucleophiles are thiolates, amines, cyanide, beta-diketones or ketoesters, etc. Those of higher basicity, Grignards, lithiates, and enolates are more basics and prefer the 1,2-addition products.