Aza-Cope Rearrangement

Aza-Cope Rearrangement

25 March, 2015 / by / in Reactions
6289
Overall Score4.5
  • Generality
  • Reagent Availability
  • Experimental User Friendliness
  • Criteria #4
  • Criteria #5

  • General Characteristics

Nitrogen-containing 1,5-dienes undergo [3,3]-sigmatropic rearrangement just like the Cope rearrangement of 1,5-dienes. Among these so-called aza-Cope rearrangements, the 3-aza version is sometimes referred to as the aza-Claisen rearrangement. In well-designed systems, the 2-aza version is known to undergo the Mannich reaction sequentially, in which case the reaction is called the aza-Cope/Mannich reaction.

  • General References

  •  Horowitz, R. M.; Geissman, T. A. J. Am. Chem. Soc. 1950, 72, 1518 DOI: 10.1021/ja01160a025

Review

  • Reaction Mechanism

Similar to other [3,3]-sigmatropic rearrangements, it is assumed that the reaction proceeds via a six-membered chair transition state (except for some specific cases in which it is not possible). The rearrangement is stereospecific for chiral compounds.

aza_cope_2.gif

  • Examples

The iminium formed by the 2-aza-Cope rearrangement can be reacted with nucleophiles in the intramolecular Mannich fashion, which has been utilized in the synthesis of extremely complex alkaloid molecules.[1] Shown below is a famous example where it was used as a key step in the synthesis of (-)-strychnine.[2]

aza_cope_3.gif

  • Experimental Procedure

  • Experimental Tips

  • References

[1] Review: Overman, L. E. Acc. Chem. Res. 1992, 25, 352. DOI: 10.1021/ar00020a005

[2] Overman, L. E. et al. J. Am. Chem. Soc. 1995, 117, 5776. DOI: 10.1021/ja00126a017

  • Related Reactions

 

  • Related Books

  • External Links

Aza-Cope rearrangement – Wikipedia

, ,