Swany
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Potential Sonogashira Reaction Problems?
For those who don't know/care to look it up, the Sonogashira reaction couples a terminal alkyne and an alkyl halide, traditionally using a Cu and Pd
catalyst. Simple enough.
Now, I have a couple questions I could not find answers to, but perhaps significant o-chem knowledge may shed some light on the issue.
1) If the alkyne and halide were at the 2 or 6 position on a pyridine molecule, would the nitrogen or planar free electron pair inhibit the reaction
or screw with it in any way? Like coordinating the Cu(I) rathe than allowing it to form the nessisery acetylide intermediate?
2) What if I was trying to couple a coordinated bipyridine, say Co(Bipy)Cl2 with a terminal alkyne at 6' and a bromide at 2 to form a ring (trimer)? I
can see some nasty unwanted side reactions, but I don't really know *what* would happen.
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Sergei_Eisenstein
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I have seen the Sonogashira reaction being used to couple alkynes with halopyridines, so I don't think Cu-complexation by the pyridine nitrogen has
to-be-avoided detrimental effects on the Cu-acetylide formation. Sonogashira coupling of ethynylpyridines has been reported. Next to that,
Cu-catalysis is not always a requirement.
The second part of the question is something you should try first and analyze the results, then hypotesize (if there are no literature references
yet).
damnant quod non intelligunt
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Shaddy
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| Quote: | | 2) What if I was trying to couple a coordinated bipyridine, say Co(Bipy)Cl2 with a terminal alkyne at 6' and a bromide at 2 to form a ring (trimer)?
I can see some nasty unwanted side reactions, but I don't really know *what* would happen. |
Your can get transmetallation, Cu-Co ligand exchange and so on. But sometimes it works. I have seen some examples with complexes, from L. De Cola, as
I remember.
You should just try. More complex start. material means more shit that you can get as products, it is quite general.
[Edited on 21-9-2007 by Shaddy]
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Sandmeyer
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| Quote: | Originally posted by Swany
1) If the alkyne and halide were at the 2 or 6 position on a pyridine molecule, would the nitrogen or planar free electron pair inhibit the reaction
or screw with it in any way? Like coordinating the Cu(I) rathe than allowing it to form the nessisery acetylide intermediate?
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What exactly are you trying to do -- to put two different alkynes on those alpha positions? i.e is your starting material
2-alkyno-6-halopyridine which you want to cross-couple with a acetylene to make it assymetric? Yes, it should work, provided that the alkyne allready
attached to pyridine isn't terminal and the incoming dosen't have 2 termina, in which case you'll get "homo-coupling", don't have scifinder right now,
but see for example takahashi et al, synthesis, 1983, p. 312. They take 2,6-dibromopyridine and couple it with trimethylsillylacetylene, subsequent
hydrolysis gave 2,6-diethynylpyridine. Those conditions could be tried on your substrate.
[Edited on 21-9-2007 by Sandmeyer]
[Edited on 21-9-2007 by Sandmeyer]
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Swany
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No, trying to put one alkyne on the 2 position and leave bromo on the 6, then couple three of them to form a planar ring with 3 metal centers that
would hopefully not be sterically opposed to being close to each other. The purpose of the alkyne group is to expand the ending sexipyridine (hah,
sexipyridine) ring to hopefully allow multiple metal centers to be chelated within it. The modified bipy ligand (with deprotected alkyne and -Br as
well as solublizing groups) is to coordinate a metal center before the coupling reaction to render it planar and thus capable of forming a trimer/ring
shaped molecule rather than a polymer of sorts that would not be useful to me.
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Sandmeyer
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I meen, to avoid unescesary misunderstandings make a jpeg with structural formulas, it is the best way to communicate still...
[Edited on 29-9-2007 by Sandmeyer]
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chemrox
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possible articles of interest
I don't know what you're trying to do but I found these at ACS:
A Copper- and Amine-Free Sonogashira Reaction of Aryl Halides Catalyzed by 1,3,5-Triaza-7-phosphaadamantane Palladium Systems
Ruiz, J.; Cutillas, N.; Lopez, F.; Lopez, G.; Bautista, D.
Organometallics; (Article); 2006; 25(24); 5768-5773. DOI: 10.1021/om060636k
Palladium-Catalyzed Alkynylation
Negishi, E.; Anastasia, L.
Chem. Rev.; (Review); 2003; 103(5); 1979-2018. DOI: 10.1021/cr020377i
Carbonylative Sonogashira Coupling of Terminal Alkynes with Aqueous Ammonia
Mohamed Ahmed, M. S.; Mori, A.
Org. Lett.; (Letter); 2003; 5(17); 3057-3060. DOI: 10.1021/ol035007a
Di-2-pyridylmethylamine-Based Palladium Complexes as New Catalysts for Heck, Suzuki, and Sonogashira Reactions in Organic and Aqueous Solvents
Najera, C.; Gil-Molto, J.; Karlstrom, S.; Falvello, L. R.
Org. Lett.; (Letter); 2003; 5(9); 1451-1454. DOI: 10.1021/ol0341849
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