Química Orgánica 2 · Condensación de Claisen y adición conjugada
Methyl 3-(2-oxocyclohexyl)propanoate by Stork enamine Michael addition
Condiciones: pyrrolidine, cat. TsOH; methyl acrylate; then H3O⁺
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El mecanismo, paso a paso
Siguiente reproduce las flechas curvas de cada paso y las explica. Los pasos escritos están abajo.
Leer los 16 pasos escritos
Pyrrolidine adds to cyclohexanone
With a catalytic amount of TsOH present (as pyrrolidinium tosylate), the pyrrolidine nitrogen attacks the ketone carbonyl carbon, giving a zwitterionic tetrahedral adduct.
Las flechas curvas
- The nitrogen lone pair forms the C–N bond.
- The C=O π pair moves onto oxygen.
Protonate the alkoxide
The pyrrolidinium catalyst gives a proton to the alkoxide.
Las flechas curvas
- The alkoxide takes the N–H proton of pyrrolidinium.
- The N–H pair returns to nitrogen.
Remove the N–H proton
Pyrrolidine removes the proton from the ammonium nitrogen, giving the neutral carbinolamine.
Las flechas curvas
- The pyrrolidine lone pair takes the N–H proton.
- The N–H pair returns to nitrogen.
Protonate the OH
Acid catalysis: pyrrolidinium protonates the carbinolamine OH so that it can leave as water, not hydroxide.
Las flechas curvas
- The OH oxygen lone pair takes the proton.
- The N–H pair returns to nitrogen.
Lose water to form the iminium ion
The nitrogen lone pair pushes out water, giving an iminium ion.
Las flechas curvas
- The nitrogen lone pair forms the C=N π bond.
- The C–O bond breaks and water leaves.
Form the enamine
Pyrrolidine removes an α-hydrogen of the iminium ion; the C–H pair forms the C=C bond and the C=N π pair returns to nitrogen, giving the enamine and regenerating pyrrolidinium.
Las flechas curvas
- The pyrrolidine lone pair takes the α-hydrogen.
- The C–H pair forms the C=C π bond.
- The C=N π pair returns to nitrogen.
Enamine adds to methyl acrylate
The nucleophilic enamine α-carbon attacks the β-carbon of methyl acrylate, pushed by the nitrogen lone pair; the acrylate C=C π pair moves to its α-carbon.
Las flechas curvas
- The nitrogen lone pair forms the C=N π bond.
- The enamine C=C π pair forms the C–C bond to the acrylate β-carbon.
- The acrylate C=C π pair moves onto its α-carbon.
Why use the enamine?
Stork enamine advantages.
Protonate the ester enolate
Pyrrolidinium protonates the ester-stabilized carbanion, leaving the iminium ion.
Las flechas curvas
- The carbanion takes the N–H proton.
- The N–H pair returns to nitrogen.
Aqueous acid workup
Hydronium from the aqueous acid protonates the free pyrrolidine.
Las flechas curvas
- The pyrrolidine lone pair takes a proton from hydronium.
- The O–H pair returns to oxygen as water.
Water adds to the iminium ion
Water attacks the iminium carbon, beginning hydrolysis back to the ketone.
Las flechas curvas
- A water lone pair forms the C–O bond.
- The C=N π pair moves onto nitrogen.
Water removes a proton from the oxonium
A second water molecule takes a proton from the added oxygen.
Las flechas curvas
- Water takes the O–H proton.
- The O–H pair stays on oxygen.
Protonate nitrogen
Hydronium protonates the amine nitrogen, making pyrrolidine a good leaving group.
Las flechas curvas
- The nitrogen lone pair takes a proton from hydronium.
- The O–H pair returns to oxygen as water.
Expel pyrrolidine
The OH oxygen lone pair re-forms C=O and pushes out neutral pyrrolidine.
Las flechas curvas
- The oxygen lone pair forms the C=O π bond.
- The C–N bond breaks and pyrrolidine leaves.
Deprotonate the ketone
The released pyrrolidine removes the proton on the carbonyl oxygen, giving the neutral keto ester and pyrrolidinium.
Las flechas curvas
- The pyrrolidine lone pair takes the O–H proton.
- The O–H pair stays on oxygen.
Methyl 3-(2-oxocyclohexyl)propanoate
The product is methyl 3-(2-oxocyclohexyl)propanoate (racemic): the enamine delivered the cyclohexanone α-carbon to the β-carbon of methyl acrylate, and the workup removed pyrrolidine.
Qué vas a practicar
Draw the Stork enamine sequence: pyrrolidine enamine formation from cyclohexanone, conjugate addition to methyl acrylate, and hydrolysis to methyl 3-(2-oxocyclohexyl)propanoate.
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