[AlphaScent]

Hey All,

Do you guys think that making the enolate from Hept-5,6-enoic Acid via LDA and then treatment with methyl iodide will give the alpha methylation? 2-methyl-hept-5,6-enoic acid?

Cheers

[phth]

Another way is to use a nucleophilic catalyst and iodine to set up a cross coupling reaction.  e.g. TMSN₃ then I₂.   Reference: doi:10.1038/nature17153

[kriggy]

I think by the procedure you describe you would mailny get ester of the acid. YOu might try to start with the ester but then you are open to some claisen condensation IMO.

[AlphaScent]

Kriggy:  I agree that I would get the ester.  But I also think the alkylation would happen.  My PI wants me to add the methyl group earlier for my synthesis design.

Reference for Alkylation of Ester enolate in presence of allene, JOC 1977, 42, 353.

[kriggy]

Are you sure its the right article? There is no alkylation described but rather dehydrogenation. It can be argued that there is new C-Se bond formed at α position but I think with MeI you will get ester as a main product.
Using excess of MeI might work if you dont mind getting methylester instead of acid

[rolnor]

You could make the TMS-ester first then add LDA and methyl iodide. Just dissolve the acid in hexamethyldisilazane and evaporate. The TMS-ester would cleave of in the aquous workup. I have used twoo eq. of LDA and some HMPA att -78 Celsius to alkylate enolates with good result, even 2-iodopropane reacts fast under this conditions. if the allene-group in your molecule will interfere I dont know, maby you just have to try.