The challenge of palladium-catalyzed aromatic azidocarbonylation: from mechanistic and catalyst deactivation studies to a highly efficient process

Fedor M Miloserdov, Claire L McMullin, Marta Martinez Belmonte, Jordi Benet-Buchholz, Vladimir I Bakhmutov, Stuart Alan Macgregor, Vladimir V Grushin

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40 Citations (Scopus)

Abstract

Azidocarbonylation of iodoarenes with CO and NaN3, a novel Heck-type carbonylation reaction, readily occurs in an organic solvent-H2O biphasic system to furnish aroyl azides at room temperature and 1 atm. The reaction is catalyzed by Xantphos-Pd and exhibits high functional group tolerance. The catalyst deactivation product, [(Xantphos)PdI2], can be reduced in situ. with PMHS to Pd(0) to regain catalytic activity. In this way, the catalyst loading has been lowered to 0.2% without any losses in selectivity at nearly 100% conversion to synthesize a series of aroyl azides in 80-90% isolated yield on a gram scale. Alternatively, the ArCON3 product can be used without isolation for further transformations in situ, e.g., to isocyanates, ureas, benzamides, and iminophosphoranes. A detailed experimental and computational study has identified two main reaction pathways for the reaction. For both routes, Ar-I oxidative addition to Pd(0) is the rate-determining step. In the presence of CO in excess, the Ar-I bond is activated by the less electron-rich Pd center of a mixed carbonyl phosphine complex. Under CO-deficient conditions, a slightly lower energy barrier pathway is followed that involves Ar-I oxidative addition to a more reactive carbonyl-free (Xantphos)Pd-0 species. Mass transfer in the triphasic liquid liquid gas system employed for the reaction plays an important role in the competition between these two reaction channels, uniformly leading to a common aroyl azido intermediate that undergoes exceedingly facile ArCO-N-3 reductive elimination. Safety aspects of the method have been investigated.

Original languageEnglish
Pages (from-to)736-752
Number of pages17
JournalOrganometallics
Volume33
Issue number3
DOIs
Publication statusPublished - 10 Feb 2014

Keywords

  • ARYLPALLADIUM(II) AZIDO COMPLEXES
  • N BOND ACTIVATION
  • ARYL HALIDES
  • REDUCTIVE ELIMINATION
  • VINYLIC HALIDES
  • CARBONYLATION REACTIONS
  • CURTIUS REARRANGEMENT
  • OXIDATIVE ADDITIONS
  • COUPLING REACTIONS
  • CRYSTAL-STRUCTURE

Cite this

Miloserdov, F. M., McMullin, C. L., Martinez Belmonte, M., Benet-Buchholz, J., Bakhmutov, V. I., Macgregor, S. A., & Grushin, V. V. (2014). The challenge of palladium-catalyzed aromatic azidocarbonylation: from mechanistic and catalyst deactivation studies to a highly efficient process. Organometallics, 33(3), 736-752. https://doi.org/10.1021/om401126m