Computational Study of Key Mechanistic Details for a Proposed Copper (I)-Mediated Deconstructive Fluorination of N-Protected Cyclic Amines

Alexey L. Kaledin, Jose B. Roque, Richmond Sarpong, Djamaladdin G. Musaev

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Using calculations, we show that a proposed Cu(I)-mediated deconstructive fluorination of N-benzoylated cyclic amines with Selectfluor® is feasible and may proceed through: (a) substrate coordination to a Cu(I) salt, (b) iminium ion formation followed by conversion to a hemiaminal, and (c) fluorination involving C–C cleavage of the hemiaminal. The iminium ion formation is calculated to proceed via a F-atom coupled electron transfer (FCET) mechanism to form, formally, a product arising from oxidative addition coupled with electron transfer (OA + ET). The subsequent β-C–C cleavage/fluorination of the hemiaminal intermediate may proceed via either ring-opening or deformylative fluorination pathways. The latter pathway is initiated by opening of the hemiaminal to give an aldehyde, followed by formyl H-atom abstraction by a TEDA2+ radical dication, decarbonylation, and fluorination of the C3-radical center by another equivalent of Selectfluor®. In general, the mechanism for the proposed Cu(I)- mediated deconstructive C–H fluorination of N-benzoylated cyclic amines (LH) by Selectfluor® was calculated to proceed analogously to our previously reported Ag(I)-mediated reaction. In comparison to the Ag(I)-mediated process, in the Cu(I)-mediated reaction the iminium ion formation and hemiaminal fluorination have lower associated energy barriers, whereas the product release and catalyst re-generation steps have higher barriers.

Original languageEnglish (US)
Pages (from-to)418-432
Number of pages15
JournalTopics in Catalysis
Volume65
Issue number1-4
DOIs
StatePublished - Feb 2022
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)

Keywords

  • Copper catalyst
  • Deconstructive fluorination
  • DFT calculation
  • N-Benzoylated cyclic amines
  • Selectfluor
  • Two-state reactivity

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