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Conjugate Addition

A long time ago I said that the key theme of Org 2 is “resonance”. Resonance can really help us explain a lot about chemical reactivity.

Key example: normally, alkenes are not very reactive towards nucleophiles (such as, say hydroxide ion (HO-). That’s because if we added hydroxide, we’d have to put negative charge somewhere – and it’s not going to be very stable on an alkane.

However, if you put a ketone or ester adjacent to the alkene, now that negative charge becomes resonance-stabilized. This means that alkenes with electron withdrawing groups on them are good electrophiles – and will react with nucleophiles.

We call this “conjugate addition”, or sometimes “1,4-addition”.

This reaction works really well with certain types of nucleophiles, like cyanide ion (CN-), alkoxides, and Gilman reagents (organocuprates). Note that the first reaction (1,4-addition or conjugate addition) we form an enolate. Then, protonation of the enolate leads to the neutral product. 

Bottom line for today:  just by putting an electron withdrawing group on an alkene, we can completely change its reactivity.

Tomorrow; what do you get when you combine enolates with conjugate addition?

Thanks for reading! James

PS One word of caution. Conjugate addition doesn’t work well for Grignard reagents, however – they tend to add to the carbonyl instead (normal addition, or sometimes “1,2-addition”).
P.S.S. Reaction Guide: Conjugate Addition