Decarbonylative Fluoroalkylation at Palladium(II): From Fundamental Organometallic Studies to Catalysis

Naish Lalloo, Christian A. Malapit, S. Maryamdokht Taimoory, Conor E. Brigham, Melanie S. Sanford*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

This Article describes the development of a decarbonylative Pd-catalyzed aryl-fluoroalkyl bond-forming reaction that couples fluoroalkylcarboxylic acid-derived electrophiles [RFC(O)X] with aryl organometallics (Ar-M′). This reaction was optimized by interrogating the individual steps of the catalytic cycle (oxidative addition, carbonyl de-insertion, transmetalation, and reductive elimination) to identify a compatible pair of coupling partners and an appropriate Pd catalyst. These stoichiometric organometallic studies revealed several critical elements for reaction design. First, uncatalyzed background reactions between RFC(O)X and Ar-M′ can be avoided by using M′ = boronate ester. Second, carbonyl de-insertion and Ar-RF reductive elimination are the two slowest steps of the catalytic cycle when RF = CF3. Both steps are dramatically accelerated upon changing to RF = CHF2. Computational studies reveal that a favorable F2C-H - -X interaction contributes to accelerating carbonyl de-insertion in this system. Finally, transmetalation is slow with X = difluoroacetate but fast with X = F. Ultimately, these studies enabled the development of an (SPhos)Pd-catalyzed decarbonylative difluoromethylation of aryl neopentylglycol boronate esters with difluoroacetyl fluoride.

Original languageEnglish (US)
Pages (from-to)18617-18625
Number of pages9
JournalJournal of the American Chemical Society
Volume143
Issue number44
DOIs
StatePublished - Nov 10 2021
Externally publishedYes

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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