Elucidating the Role of the Boronic Esters in the Suzuki-Miyaura Reaction: Structural, Kinetic, and Computational Investigations

Andy A. Thomas, Andrew F. Zahrt, Connor P. Delaney, Scott E. Denmark

Research output: Contribution to journalArticle

Abstract

The Suzuki-Miyaura reaction is the most practiced palladium-catalyzed, cross-coupling reaction because of its broad applicability, low toxicity of the metal (B), and the wide variety of commercially available boron substrates. A wide variety of boronic acids and esters, each with different properties, have been developed for this process. Despite the popularity of the Suzuki-Miyaura reaction, the precise manner in which the organic fragment is transferred from boron to palladium has remained elusive for these reagents. Herein, we report the observation and characterization of pretransmetalation intermediates generated from a variety of commonly employed boronic esters. The ability to confirm the intermediacy of pretransmetalation intermediates provided the opportunity to clarify mechanistic aspects of the transfer of the organic moiety from boron to palladium in the key transmetalation step. A series of structural, kinetic, and computational investigations revealed that boronic esters can transmetalate directly without prior hydrolysis. Furthermore, depending on the boronic ester employed, significant rate enhancements for the transfer of the B-aryl groups were observed. Overall, two critical features were identified that enable the transfer of the organic fragment from boron to palladium: (1) the ability to create an empty coordination site on the palladium atom and (2) the nucleophilic character of the ipso carbon bound to boron. Both of these features ultimately relate to the electron density of the oxygen atoms in the boronic ester.

Original languageEnglish (US)
Pages (from-to)4401-4416
Number of pages16
JournalJournal of the American Chemical Society
Volume140
Issue number12
DOIs
StatePublished - Mar 28 2018

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Boron
palladium
Palladium
boron
ester
Esters
kinetics
Kinetics
Boronic Acids
Atoms
Cross Reactions
electron density
Carrier concentration
Toxicity
hydrolysis
Hydrolysis
Carbon
Metals
Observation
Electrons

ASJC Scopus subject areas

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

Cite this

Elucidating the Role of the Boronic Esters in the Suzuki-Miyaura Reaction : Structural, Kinetic, and Computational Investigations. / Thomas, Andy A.; Zahrt, Andrew F.; Delaney, Connor P.; Denmark, Scott E.

In: Journal of the American Chemical Society, Vol. 140, No. 12, 28.03.2018, p. 4401-4416.

Research output: Contribution to journalArticle

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