I remember at one point having a (review?) paper called “Pyridine!” in my collection. Love that title. I can’t remember who wrote it, what year it was from or what it contained. Now I can’t find it again, because SciFinder and Google Scholar seem to ignore the exclamation mark in text based searches. If you know of a workaround or how else to rediscover this article, please tell me.

Anyways, pyridines and pyridones lie close to my heart, and I am delighted to see the latest progress in synthesis of highly substituted pyridines. I think it was Manfred Schlosser, the crowned King of pyridines, who coined the term “regioexhaustive functionalizations”, which I try to reuse as often as possible.

During this fall in Organic Letters alone there appear at least three excellent papers on the topic.

Org. Lett. 2011, 13, 5394–5397. (DOI: 10.1021/ol202290y)
Org. Lett., Article ASAP (DOI: 10.1021/ol202691b)
Org. Lett., Article ASAP (DOI: 10.1021/ol202679t)

Normally, I would paste the graphical abstracts here, but as time is not on my side right now, you will have to suffice with uncovering these manually – this time only. I can however vouch for the awesomeness of all three, if you are at all into heterocyclic chemistry.

Finally, I would like reveal my hidden agenda and turn your attention and this post into a blatant plug for one of our own publications. Ha! We were the first to synthesize pyridines substituted with five different elements (1 and 2).

Pyridines substituted with five different elements

Synthesis 2010, 63-66. (DOI: 10.1055/s-0029-1217084).

What we did not realize until the paper had been accepted and proofed was that we missed a golden opportunity to introduce a sixth element. Do you see it?

Upon treatment of pyridine 2 with MCPBA, you would get a pyridine substituted with six different elements, the N-oxide, right? Any takers? (Please mention us when you publish.)

 

3 Responses to Pyridine!

  1. milkshake says:

    the treatment of pyridine 2 with m-CPBA you will get you sulfoxide and then immediately the sulfone. You would have to beat much harder on it to get it all the way to N-oxide-sulfone.

    There is a lovely preparation where you oxidize 2-methylthio-4,6-dichloropyrimidine with mCPBA to the Me-sulfone (without harming the ring nitrogens and then you displace the produced methylsulfone in 2-position with a (poorly reactive) amine under mild conditions, this substitution leaves the two chlorines unmolested.

  2. milkshake says:

    also there is a risk that N-oxidation attempt would produce desilylated products, possibly 2-hydroxypyridine too.

  3. drfreddy says:

    Do you think I would post the perfect recipe just like that? :)

    You’re right, of course. MCPBA is a poor choice. But… I can’t think of anything right now that would prefer N over S.

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