Pre-transmetalation intermediates in the Suzuki-Miyaura reaction revealed: the missing link

Thomas, Andy Alexander

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https://hdl.handle.net/2142/97541 Copy

Description

Title

Pre-transmetalation intermediates in the Suzuki-Miyaura reaction revealed: the missing link

Author(s)

Thomas, Andy Alexander

Issue Date

2017-03-17

Director of Research (if dissertation) or Advisor (if thesis)

Denmark, Scott E.

Doctoral Committee Chair(s)

Denmark, Scott E.

Committee Member(s)

• Burke, Martin D.
• Sarlah, David
• Rauchfuss, Thomas B.

Department of Study

Chemistry

Discipline

Chemistry

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

Transmetalation

Abstract

The Suzuki-Miyaura reaction is currently the most practiced cross-coupling reaction due to its broad applicability, low toxicity of the metal (B), and the wide variety of commercially available boronic acid substrates. 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 over 30 years. The work described in this dissertation has focused on identifying such species by low temperature rapid injection NMR spectroscopy. For the first time, we were able to detect and characterize the first pre-transmetalation intermediate “The Missing Link” in the Suzuki-Miyaura reaction. The ability to confirm the intermediacy of pre-transmetalation intermediates has provided the opportunity to clarify mechanistic aspects of the transfer of the organic moiety from boron to palladium in the key transmetalation step. Specifically, these studies establish the identity of two different intermediates containing Pd−O−B linkages, a tricoordinate (6-B-3) boronic acid complex and a tetracoordinate (8-B-4) boronate complex, both of which undergo transmetalation leading to the cross-coupling product. Two distinct mechanistic pathways have been elucidated for stoichiometric reactions of these complexes: (1) transmetalation via an unactivated 6-B-3 intermediate that dominates in the presence of excess ligand, and (2) transmetalation via an activated 8-B-4 intermediate that takes place with a deficiency of ligand. The successful formation of pre-transmetalation intermediates with arylboronic acids led to the investigation of whether some of the most common arylboronic esters utilized in the Suzuki-Miyaura reaction could also form stable intermediates. Surprisingly, catechol and ethylene glycol arylboronate esters formed Pd-O-B linkages at low temperature and were found to transfer their organic groups directly from boron to palladium with enhanced rates. Specifically, the glycol arylboronate ester was found to transfer its organic group ~25 times faster than the corresponding arylboronic acid analog. These combined results provide the first structure activity relationships on the pre-transmetalation intermediates in the Suzuki-Miyaura reactions which are currently being applied to catalytic reactions.

Graduation Semester

2017-05

Type of Resource

text

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http://hdl.handle.net/2142/97541

Copyright and License Information

Copyright 2017 Andy Thomas

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