Chemoselectivity for Alkene Cleavage by Palladium-Catalyzed Intramolecular Diazo Group Transfer from Azide to Alkene

Grant B Frost, Michaela N. Mittelstaedt, Christopher J Douglas

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Alkenes can be cleaved by means of the (3+2) cycloaddition and subsequent cycloreversion of 1,3-dipoles, classically ozone (O 3 ), but the azide (R−N 3 ) variant is rare. Chemoselectivity for these azide to alkene diazo group transfers (DGT) is typically disfavored, thus limiting their synthetic utility. Herein, this work discloses a palladium-catalyzed intramolecular azide to alkene DGT, which grants chemoselectivity over competing aziridination. The data support a catalytic cycloreversion mechanism distinct from other known metal-catalyzed azide/alkene reactions: nitrenoid/metalloradical and (3+2) cycloadditions. Kinetics experiments reveal an unusual mechanistic profile in which the catalyst is not operative during the rate-controlling step, rather, it is active during the product-determining step. Catalytic DGT was used to synthesize N-heterocyclic quinazolinones, a medicinally relevant structural core. We also report on the competing aziridination and subsequent ring expansion to another N-heterocyclic core structure of interest, benzodiazepinones.

Original languageEnglish (US)
Pages (from-to)1727-1732
Number of pages6
JournalChemistry - A European Journal
Issue number7
StatePublished - Feb 1 2019

Bibliographical note

Funding Information:
The authors wish to express thanks to the National Institutes of Health (R01 GM095559), thanks to Prof. S. R. Kass (UMN) for instrument use as well as insightful conversation, and thanks to Dr. N. R. Rondla for mentorship and discussions.


  • alkene cleavage
  • azides
  • cycloreversion
  • diazo group transfer
  • palladium


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