Using Michael acceptors as electrophiles
المؤلف:
Jonathan Clayden , Nick Greeves , Stuart Warren
المصدر:
ORGANIC CHEMISTRY
الجزء والصفحة:
ص605-606
2025-06-28
525
α, β-Unsaturated carbonyl compounds are, as you have just seen, an excellent source of regio defined enolate equivalents. But they are also very effective electrophiles for reaction with enolates. In this last section we will consider conjugate addition reactions of enolates as an alternative way of making C–C bonds.
As with other conjugate additions, it is important in such reactions to choose conditions that prevent the nucleophile (here the enolate) attacking the C=O group directly. The same factors discussed govern the eventual outcome of the reaction. Thermodynamic control leads to conjugate addition but kinetic control leads to direct addition, so the key to successful conjugate addition is to ensure that direct addition to the carbonyl group is reversible. This enables the conjugate addition to compete and, as its product is more stable (it loses the weaker C=C π bond rather than the stronger C=O π), it eventually becomes the sole product.
One of the most important ways of making the direct addition reversible is to use a more stabilized enolate, since expulsion of the stable anion from the direct addition product is more favourable. An additional consequence of adding a second electron-withdrawing group such as CO2Et is that the direct addition product is more hindered (and therefore less stable) than the conjugate addition product.
The nature of the carbonyl group in the α,β-unsaturated electrophile is also important as the more electrophilic carbonyl groups give more direct addition and the less electrophilic carbonyl groups (esters, amides) give more conjugate addition. Aldehydes and ketones can be pushed towards conjugate addition pathways by careful choice of enolate equivalent, while esters and amides are much less electrophilic at the carbonyl carbon and so are good sub strates for conjugate addition.
●Conjugate addition is thermodynamically controlled; direct addition is kinetically controlled. Stabilized enolates promote conjugate addition by:
• making direct addition (aldol reaction) more reversible
• making the direct addition (aldol) product more hindered.
Less reactive Michael acceptors promote conjugate addition by:
• making direct addition (aldol reaction) more reversible
• making the carbonyl group less electrophilic.
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