Symmetry in intramolecular crossed Claisen condensations
المؤلف:
Jonathan Clayden , Nick Greeves , Stuart Warren
المصدر:
ORGANIC CHEMISTRY
الجزء والصفحة:
ص653-654
2025-07-01
573
If cyclization is to be followed by decarboxylation, a cunning plan can be set in motion. Addition of an amine by an SN2 reaction to an α halo-ester followed by conjugate addition to an unsaturated ester gives a substrate for Claisen ester cyclization.
This diester is unsymmetrical so cyclization is likely to lead to two different keto-esters. Either can form a stable enolate so both are indeed formed. This sounds like very bad news since it gives a mixture of products.
The cunning plan is that the relative positions of the ketone and the nitrogen atom in the five-membered ring are the same in both products. All that differs is the position of the CO2Et group. When the two different products are hydrolysed and decarboxylated they give the same amino-ketone!
Just occasionally it is possible to carry out cross-condensations between two different enolizable molecules under equilibrating conditions. A notable example is the base-catalysed reaction between methyl ketones and lactones. With sodium hydride—a strong base that can convert either starting material entirely into its enolate anion—good yields of products from the attack of the enolate of the ketone on the electrophilic lactone can be obtained.
Kinetic enolate formation must occur at the methyl group of the ketone followed by acylation with the lactone. Lactones are rather more electrophilic than non-cyclic esters, but the control in this sequence is still remarkable. Notice how a stable enolate is formed by proton transfer within the first-formed product.
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