Mechanistic investigations of cooperative catalysis in the enantioselective fluorination of epoxides

Julia A. Kalow, Abigail Gutmann Doyle

Research output: Contribution to journalArticle

101 Scopus citations

Abstract

This report describes mechanistic studies of the (salen)Co- and amine-cocatalyzed enantioselective ring opening of epoxides by fluoride. The kinetics of the reaction, as determined by in situ 19F NMR analysis, are characterized by apparent first-order dependence on (salen)Co. Substituent effects, nonlinear effects, and reactivity with a linked (salen)Co catalyst provide evidence for a rate-limiting, bimetallic ring-opening step. To account for these divergent data, we propose a mechanism wherein the active nucleophilic fluorine species is a cobalt fluoride that forms a resting-state dimer. Axial ligation of the amine cocatalyst to (salen)Co facilitates dimer dissociation and is the origin of the observed cooperativity. On the basis of these studies, we show that significant improvements in the rates, turnover numbers, and substrate scope of the fluoride ring-opening reactions can be realized through the use of a linked salen framework. Application of this catalyst system to a rapid (5 min) fluorination to generate the unlabeled analog of a known PET tracer, F-MISO, is reported.

Original languageEnglish (US)
Pages (from-to)16001-16012
Number of pages12
JournalJournal of the American Chemical Society
Volume133
Issue number40
DOIs
StatePublished - Oct 12 2011

All Science Journal Classification (ASJC) codes

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

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