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How to Tackle Organic Syntheses - A Beginner's Guide by Prof Otto Meth-Cohn

The Wittig Reaction


Georg Wittig well deserved his Nobel Prize in 1979 - and is a hero of mine because he was a doddering 56 years old when he discovered this very versatile reaction. The idea is very simple - as are all good ideas. Phosphorus is a second row element - in Group 5 - like nitrogen - but unlike nitrogen can expand its valency from 3 to 4, 5, or even 6. The stable 5 valency is met in compounds like phosphoric acid and PCl5. What Wittig discovered was that phosphines (the P equivalent of amines) easily form phosphonium salts with alkyl halides and that these salts readily lose HX with a strong base. The product is called an ylide or a phosphorane. The ylide is a very polar molecule with a carbanionic carbon (aren't carbanions useful?!).

How to make a phosphorus ylide

This ylide reacts enthusiastically with an aldehyde or ketone to give an alkene.

How to make an alkene using the Wittig reaction

You'll notice that the reaction involves formation of a 4-membered ring intermediate and that the very stable phosphine oxide is a by-product. The great thing for hard-pressed student synthesizers is that the alkene is made up by linking an aldehyde or ketone to an alkyl halide replacing the O and the halide by a double bond. Just snip the alkene at the double bond and make one half an aldehyde or ketone and the other half an alkyl halide.

note the special arrow used when we work backwards more of that later in our course

The reason that the reaction goes so well is due to the formation of the immensely strong P-O bond. The strong base used to make the ylide could be sodium hydride (NaH) or sodamide (NaNH2). Given a more acidic H to abstract, a weaker base such as NaOEt or even Na2CO3 could be used.

Another variant on the Wittig reaction that is much easier and cheaper to carry out is called the Wittig-Horner reaction. This uses a phosphite ester instead of a phosphine:

The Wittig-Horner reaction

The ylide is much more reactive in this case.

What about stereochemistry? Cis/trans, E/Z etc. Well, that's an interesting issue though still not fully clear. Triphenylphosphines tend normally to give the Z- (or cis-) isomer. Trialkylphosphines or the presence of groups that stabilise the ylide tends to give E- (or trans-) geometry. So take your pick! What makes the Wittig reaction so useful is that it can tolerate all kinds of functionality.

You'll see that since an alkene can be converted into an alkane, an alkyl halide, a dihaloalkane, an epoxide etc. etc. we have an especially useful item in that bag of ours. In fact, armed with these three tools - the Grignard, enolate and Wittig reactions we can - as the Yanks would say - do most anything! So let's try out our nice new tool.

Q6. How would you synthesize these compounds using a Wittig reaction?

P.S. You'll have to think a bit for the second one; and for the third - invent a double bond then remove it later!

Let's now try to put everything together!


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Ol' Spidey: page last changed 5 April 1997