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Aza-Diels–Alder reaction

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The Aza Diels-Alder reaction converts imines and dienes to tetrahydropyridines. This organic reaction is a modification of the Diels-Alder reaction. The nitrogen atom can be part of the diene or the dienophile.

The Aza Diels-Alder reaction, general scope
The Aza Diels-Alder reaction, general scope

The imine is often generated in situ from an amine and formaldehyde. An example is the reaction of cyclopentadiene with benzylamine to an aza norbornene.[1]

In the enantioselective Diels-Alder (DA) reaction of an aniline, formaldehyde and a cyclohexenone catalyzed by (S)-proline even the diene is masked.[2]

S-proline enantioselective Aza Diels-Alder reaction
S-proline enantioselective Aza Diels-Alder reaction

The catalytic cycle starts with the reactions of the aromatic amine with formaldehyde to the imine and the reaction of the ketone with proline to the diene. The second step, an endo trig cyclisation, is driven to one of the two possible enantiomers (99% ee) because the imine nitrogen atom forms a hydrogen bond with the carboxylic acid group of proline on the Si face. Hydrolysis of the final complex releases the product and regenerates the catalyst.

catalytic cycle for S-proline enantioselective Aza Diels-Alder reaction
catalytic cycle for S-proline enantioselective Aza Diels-Alder reaction

See also

References

  1. ^ N-benzyl-2-azanorbornene Paul A. Grieco and Scott D. Larsen Organic Syntheses, Coll. Vol. 8, p.31; Vol. 68, p.206 Article
  2. ^ Direct Catalytic Enantioselective Aza-Diels-Alder Reactions Henrik Sundén, Ismail Ibrahem, Lars Eriksson, Armando Córdova Angewandte Chemie International Edition 4877 2005 Abstract