There is nothing I hate more than not being able to draw a plausible mechanism for a seemingly simple transformation. (That is not entirely true; I hate coriander, jazz music and water-boarding too, but you get the point.)
We have this reaction we know works, but I fail to get the curly arrows right. It bothers me a great deal. For a number of reasons, I cannot provide the exact structure or literature reference here, but the essence of the reaction is as depicted above. An acid-catalyzed ring-contraction to a (fused) thiazole in good isolated yield in gram scale. Several other functional groups are polite bystanders, suggesting relatively benign conditions. I feel somewhat confident that the first two steps must be an internal sulfur nucleophilic attack on the protonated imine followed by ring opening by water, and by all means do correct me if you think otherwise…
…but then what? The proposed acetal intermediate could maybe be hydrolyzed to its corresponding ketone, sure. However, that does not really help us much, does it? I am, frankly, completely lost.
Something appears to be fishy with the oxidation level. Agreed? No matter how I draw it, at some point a hydride or a carbon anion (God forbid under acidic conditions) is a leaving group, and I am no big fan of those. Alternatively, you could kick out the top ester, but that would involve the generation of carbon monoxide… ugh. While deformylation occurs readily in vivo, it does so rarely in the flask, in my humble experience. We have no oxidant in the mix (well we have air, if that helps). Also, if the top ester is the leaving group, why is the final compound an ester?
For the record, I have drawn even stupider mechanisms involving carbenes or nitrenes, but I hate them even more.
I need your help to understand this one. Feel free to use imgur or some other image provider, and post links below to pictures of better suggestions. Or just type it up. The correct answer, preferably! 🙂
I have great confidence in you. I know you can outperform me here. Do it! Thanks.