Mechanism and selectivity of N -triflylphosphoramide catalyzed (3+ + 2) Cycloaddition between hydrazones and alkenes

Xin Hong, Hatice Başpinar Küçük, Modhu Sudan Maji, Yun Fang Yang, Magnus Rueping*, K. N. Houk

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

71 Scopus citations


Brønsted acid catalyzed (3+ + 2) cycloadditions between hydrazones and alkenes provide a general approach to pyrazolidines. The acidity of the Brønsted acid is crucial for the catalytic efficiency: the less acidic phosphoric acids are ineffective, while highly acidic chiral N-triflylphosphoramides are very efficient and can promote highly enantioselective cycloadditions. The mechanism and origins of catalytic efficiencies and selectivities of these reactions have been explored with density functional theory (M06-2X) calculations. Protonation of hydrazones by N-triflylphosphoramide produces hydrazonium-phosphoramide anion complexes. These ion-pair complexes are very reactive in (3+ + 2) cycloadditions with alkenes, producing pyrazolidine products. Alternative 1,3-dipolar (3 + 2) cycloadditions with the analogous azomethine imines are much less favorable due to the endergonic isomerization of hydrazone to azomethine imine. With N-triflylphosphoramide catalyst, only a small distortion of the ion-pair complex is required to achieve its geometry in the (3+ + 2) cycloaddition transition state. In contrast, the weak phosphoric acid does not protonate the hydrazone, and only a hydrogen-bonded complex is formed. Larger distortion energy is required for the hydrogen-bonded complex to achieve the ion-pair geometry in the cycloaddition transition state, and a significant barrier is found. On the basis of this mechanism, we have explained the origins of enantioselectivities when a chiral N-triflylphosphoramide catalyst is employed. We also report the experimental studies that extend the substrate scope of alkenes to ethyl vinyl ethers and thioethers.

Original languageEnglish (US)
Pages (from-to)13769-13780
Number of pages12
JournalJournal of the American Chemical Society
Issue number39
StatePublished - Sep 2 2014
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2014 American Chemical Society.

ASJC Scopus subject areas

  • Catalysis
  • General Chemistry
  • Biochemistry
  • Colloid and Surface Chemistry


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