Organometallics and Wittig reactions in synthesis

Grignard reagents are among the most frequently used reagents in organic synthesis. They react with a wide variety of substrates; however, in this section, we are concerned only with those reactions that produce alcohols. Notice that in a reaction involving a Grignard reagent, not only does the functional group get changed, but the number of carbon atoms present also changes. This fact provides us with a useful method for ascending a homologous series. For example:

One important route for producing an alcohol from a Grignard reagent has been omitted from the discussion in the reading. It involves the reaction of the Grignard reagent with ethylene oxide to produce a primary alcohol containing two more carbon atoms than the original Grignard reagent.

As mentioned in the reading, both organolithium and Grignard reagents are good nucleophiles. They also act as strong bases in the presence of acidic protons such as −CO₂H, −OH, −SH, −NH and terminal alkyne groups. Not only do acidic protons interfere with the nucleophilic attack on the carbonyl of these organometallic reagents, if the starting materials possess any acidic protons, reagents cannot be generated in the first place. They are also the reason these reactions must be carried out in a water‑free environment.

Another limitation of preparing Grignard and organolithium reagents is that they cannot already contain a carbonyl group  because it would simply react with itself.

A summary of the methods used to prepare alcohols from Grignard reagents is provided below.

Many of these alcohols can be converted to an alkene, by heating with an acid such as H₂SO₄ or H₃PO₄., via an E1 elimination.  However, this can often give mixtures of isomeric alkene products with the double bond at different positions.  Therefore, when the target product of a C-C bond forming reaction is an alkene, it is usually better to use a Wittig reaction instead, because this will form the new double bond unambiguously at one position.