[Urbanium]

Hello, I have to propose a retrosynthesis for one compound. This (attachment) is the best I was able to do.

Is there some better way to do some steps? I was concerned about some issues, especially the second and third step and also esterification (not sure about acidic medium used in esterification, given that the substrate is an α,β-unsaturated aldehyde, will it influence its stability)? What is the stereochemical aspect of these processes, will I get the preferred isomer? Thanks for suggestions.

[Archer]

Do you have any specific instructions to follow? i.e. all starting materials must be no more than 3 carbons etc.

[Urbanium]

I only have the structure of the final product and a suggestion to start with as simpler starting compounds as possible, e.g. methyl vinyl ketone or something similar.

[Urbanium]

If somebody could actually just tell me what are the prospectives for the last synthesis step, i.e. is it safe to perform a Fischer esterification catalyzed by sulfuric acid if a compound at a same time has hydroxy group (which we want to be a part of an ester) and at the same time is an enal (α,β-unsaturated aldehyde)?

[Archer]

If somebody could actually just tell me what are the prospectives for the last synthesis step, i.e. is it safe to perform a Fischer esterification catalyzed by sulfuric acid if a compound at a same time has hydroxy group (which we want to be a part of an ester) and at the same time is an enal (α,β-unsaturated aldehyde)?

No, but there are many much milder conditions which could be used.

Can you think of any reagents used to make esters which are derived from carboxylic acids?

[Urbanium]

as far as I know there is a possibility of carbonilation, transesterification, reaction of alcohols with acyl chlorides or anhydrides...

But I'm not sure if it's suitable to react my alcohol (which is an enal at the same time) with acyl chloride or acetic anhydride in the above process? Will only the hydroxy group react?

[Archer]

Acid anhydrides are extremely mild and selective, particularly if a base such as pyridine is used in conjunction with catalytic dimethylaminopyridine (DMAP)

[Urbanium]

Ok, thanks. I hope acetic anhydride is not prone to react with enal part of the substrate molecule.

[Archer]

The enal will not act as a nucleophile so you are safe there and the pyridine will mop up the acetic acid produced.