[curiouscat]

I'm having a basic org chem amnesia moment: If I were to condense and   acid catalyzed,  would I expect to see (Product a) or (Product b) or both.

If both, any way to estimate (roughly) the ratios or which would be the dominant product?

I think I ought to get (Product a) but not sure if the other crossed Product (b) will form too.

I'm assuming I did get the crossed products right. I hope.

[curiouscat]

Sigh. More I think about it the more I'm confused. Too many alpha Hydrogens that may be abstracted away. Too many combinations.

How about these products?

(Product c) or the self condensation options (Product d) or  (Product e) or (Product f)

Am I missing something obvious? I feel I'm going overboard with the combinations.  Is it all dependent on the relative pKa values for various C-H bond abstraction possibilities among all the alpha Hydrogens.

[curiouscat]

On deeper digging I found this quote that might help my conundrum:

Since the carbonyl carbon of aldehyde is more electrophilic than that of ketone, the reaction between an aldehyde an a ketone is synthetically viable. The α-carbon of ketone usually adds to the carbonyl carbon of aldehyde, leading to only one major product.

If so, that'd mean (Product a) and ( Product c) are the ones? Right?

Any clue if one or the other might dominate? Sterically, (Product c) seems more likely, the terminal alpha-H seems more accessible. OTOH, is the secondary-Carbon alpha-H easier to abstract away?

[Dan]

I would expect predominantly product A, which would arise from the condensation of the thermodynamically most stable enol with acetaldehyde. I would not be surprised if it was quite messy though.

[curiouscat]

I would expect predominantly product A, which would arise from the condensation of the thermodynamically most stable enol with acetaldehyde. I would not be surprised if it was quite messy though.

Thanks Dan.

A question: Isn't self condensation of both the aldehyde and the ketone likely here? Or are they hindered or unfavorable in some way relative to the cross condensation.

[orgopete]

I would expect predominantly product A, which would arise from the condensation of the thermodynamically most stable enol with acetaldehyde. I would not be surprised if it was quite messy though.

Quite messy indeed. If anyone has a reference to a good acid catalyzed aldol condensation, I'm interested. Most are done under basic conditions. If you write a mechanism for an acid catalyzed condensation, you might conclude the concentration of intermediates may result in a slow reaction. Perhaps this contributes to the relatively small number of examples. The reactions that succeed may form additional products especially as some reaction conditions are quite vigorous.

[curiouscat]

I would expect predominantly product A, which would arise from the condensation of the thermodynamically most stable enol with acetaldehyde. I would not be surprised if it was quite messy though.

Quite messy indeed. If anyone has a reference to a good acid catalyzed aldol condensation, I'm interested. Most are done under basic conditions. If you write a mechanism for an acid catalyzed condensation, you might conclude the concentration of intermediates may result in a slow reaction. Perhaps this contributes to the relatively small number of examples. The reactions that succeed may form additional products especially as some reaction conditions are quite vigorous.

@orgopete:

Out of curiosity, if you did a base catalyzed condensation with these reactants, which major products would you expect? Would I need a subsequent acid step to dehydrate the aldol? Or would the base accomplish both parts?

[orgopete]

A crossed aldol with base and both carbonyls are enolizable? I'd look for another synthesis.

[curiouscat]

A crossed aldol with base and both carbonyls are enolizable? I'd look for another synthesis.

Have any options in mind? I'd love to consider. My aldehyde and ketone reactants are both commodity chemicals available fairly cheap. It's going to be mighty hard competing against those feedstocks. 

That's one big upside of my route, I think. But, I may be wrong.

This may not be a huge project, but still a couple of tons a month is what we might need to make. So definitely not an academic exercise.

[orgopete]

Can you acylate dimethylacetylene or a similar disconnection?