Org Prep Daily

November 25, 2006

For a few carbons more

Filed under: mechanisms — milkshake @ 7:27 am

I was trying to make diazaindoles from diaminobromopyrimidines by Pd-catalyzed arylation of a cyclic 1,3-diketone (dimedone) when I met these cyclized strangers:

dimedone1d.gif

Apparently the cyclization product resulted from a reductive Heck coupling with a condensation product of acetaldehyde plus dimedone. I used a fairly high Pd(II) pre-catalyst loading (10 mol%) so I guess the acetaldehyde equivalent was generated by the Pd(II)-promoted oxidation of triethylamine.

dimedone2d.gif

In this wild story the addition product does not beta-eliminate Pd(0) – as in typical Heck reaction – but undergoes a protonolysis instead. Pd(II) re-emerges from the sequence at the end, ready to hunt down and oxidize another molecule of triethylamine. (Credits: Dr. Ni for ROESY)

5 Comments »

  1. at first blush, I was curious… is the hydrazine available for fischer indole synethesis? the 2-amino,4-hydrazinyl-pyrmidine?

    just a thought…

    Comment by Luke — November 25, 2006 @ 4:17 pm

  2. I think Fisher indole synthesis would not work on these pyrimidines too well – the hydrazone cyclization is an electrophilic Ar substitution after all and pyrimidines have a terribly desactivated ring. The acidic/Lewis-acidic catalysts in Fisher synthesis would desactivate it even further.

    Comment by milkshake — November 25, 2006 @ 10:10 pm

  3. Nice detective work.

    Comment by kinasepro — November 27, 2006 @ 1:47 am

  4. I am curious whether you worked out the disired product by using other bases.

    BTW, any idea bezyne chemistry is going to work on pyrimidine?

    Comment by diketenes — November 30, 2006 @ 9:52 pm

  5. I don’t think benzyne happens here. Testing other conditions: I think I tried couple of catalysts and bases and I did not see much happening – either there was no reaction, or I got a baseline schmutz (or streak on TLC and a forrest of peaks on HPLC) or I obtained the product of halogen reduction. But I have not done any systematic study and comparison with other amine bases. I know what you mean – this thing should not be happening if NEt3 is replaced with something else.

    Comment by milkshake — December 1, 2006 @ 2:09 pm


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