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Title:Pre-transmetalation intermediates in the Suzuki-Miyaura reaction revealed: the missing link
Author(s):Thomas, Andy Alexander
Director of Research:Denmark, Scott E
Doctoral Committee Chair(s):Denmark, Scott E
Doctoral Committee Member(s):Burke, Martin D; Sarlah, David; Rauchfuss, Thomas B
Department / Program:Chemistry
Discipline:Chemistry
Degree Granting Institution:University of Illinois at Urbana-Champaign
Degree:Ph.D.
Genre:Dissertation
Subject(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.
Issue Date:2017-03-17
Type:Thesis
URI:http://hdl.handle.net/2142/97541
Rights Information:Copyright 2017 Andy Thomas
Date Available in IDEALS:2017-08-10
Date Deposited:2017-05


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