Hyperconjugative Antiaromaticity Activates 4 H-Pyrazoles as Inverse-Electron-Demand Diels-Alder Dienes

Org Lett. 2019 Oct 18;21(20):8492-8495. doi: 10.1021/acs.orglett.9b03351. Epub 2019 Oct 7.


The Diels-Alder reactivity of 4,4-difluoro-3,5-diphenyl-4H-pyrazole was investigated experimentally and computationally with endo-bicyclo[6.1.0]non-4-yne. The computationally predicted rate enhancement from hyperconjugative antiaromaticity induced by fluorination of cyclopentadienes at the 5-position extends to five-membered heterocyclic dienes containing a saturated center. 4,4-Difluoro-4H-pyrazoles are new electron-deficient dienes with rapid reactivities toward strained alkynes.