[quantumnumber]

Hi everyone,

I thought of two synthesis routes driving to the same product (see the attachment). One is an alkylation, and the other a conjugate addition. Which one do you think it's better? Both would work?

Thanks a lot!

[discodermolide]

Probably the alkylation. Methyl vinyl ketones are very prone to polymerisation.

[rwiew]

I agree, the Michael might get problematic.

[AlphaScent]

I am actually doing a reaction very similar to your alkylation and it works great. 

I do it all in situ too.  No isolation until the final decarboxylated product.

Very clean reaction.  87% yield.

[quantumnumber]

Thank all of you for your answers

[orgopete]

I am actually doing a reaction very similar to your alkylation and it works great. 

I do it all in situ too.  No isolation until the final decarboxylated product.

Very clean reaction.  87% yield.

I would not have expected this with a beta-bromoketone. Did you simply add additional bromide and base to overcome elimination, or am I completely wrong on how easy it is to eliminate a bromide in basic solution?

I actually would have preferred the conjugate addition route although it might have been complicated by a concomitant aldol reaction. As an alternative, I'd protect the ketone.

[AlphaScent]

I maybe used the word similar a little loosely...

Mine is 1-bromo-3-hexene.  Elimination was prevalent with the mesylate.  We have to use bromide.

[AlphaScent]

I also think this could be one of those reactions where you have to try it and see.

[orgopete]

In that case, the conjugate addition. I don't think the bromide would work. Even if the bromide were used, it would eliminate quite quickly and consume base. Conjugate addition only requires a catalytic amount of base, so even the proposed alkylation could go by conjugate addition.

[AlphaScent]

Its still primary.  I think you may be surprised.  Mine doesnt eliminate as readily as one may think.

Try both.

[orgopete]

Its still primary.  I think you may be surprised.  Mine doesnt eliminate as readily as one may think.

I didn't expect yours would eliminate very easily, but I did think 4-bromo-2-butanone will eliminate a lot more easily than your 1-bromo-3-hexene.

[zsinger]

Alkylation is usually pretty fool proof.  High yields usually in my experiences.  Conjugate can be finicky.
         -Zack

[orgopete]

And yet I persist? I am surprised that no one picks up that treating a beta-bromoketone with ethoxide will cause an elimination. I think, perhaps this reaction is referenced in Organic Synthesis? I do a search in OrgSyn for methyl vinyl ketone. Although that was not helpful, it showed examples of pretty good yields in conjugate additions, for example see http://www.orgsyn.org/demo.aspx?prep=V78P0249. Obviously this is not the proposed reaction. The alpha methyl group will likely interfere with a conjugate addition, but it will also interfere with an elimination by reducing the acidity of the alpha hydrogen and will slow the alkylation reaction. Compare the rates of propyl, isobutyl, and t-amyl bromide.

@alpha, this is how I think this reaction is different. If the bromide is used, the reaction can still succeed if elimination is much faster than alkylation (via conjugate addition). In your reaction, I think elimination reduces the overall conversion of bromide.

Now, I sure hope this is a real reaction that is going to be performed so we can see the lab results.