A General Protocol for Addressing Speciation of the Active Catalyst Applied to Ligand-Accelerated Enantioselective C(sp3)–H Bond Arylation

David E. Hill, Qing-lan Pei, En-xuan Zhang, James R. Gage, Jin-Quan Yu, and Donna G. Blackmond

ACS Catalysis,
2018, 8, (2), 1528; DOI:10.1021/acscatal.8b00103

01/2018

Catalysts are tools developed by chemists that expediate the production of materials and energy used in daily life. Catalysts serve this important role by providing access to a lower energy reaction pathway that was previously unavailable, thereby decreasing the overall energy required for the chemical transformation. Understanding the way current catalysts work, or their mechanism, is critical to their advancement and diversification. Thus, research in advancing and understanding catalysts has led to the development of various methods for interrogating catalyst mechanisms. One such method is chemical kinetics, or the study of reaction rates, which is the primary tool employed by the Blackmond lab to investigate catalyst mechanisms. Through observing reaction rates under different conditions, the Blackmond lab builds experimentally-derived mathematical models that plausibly describe the individual steps of an entire catalyst mechanism. Previous investigations by the Blackmond lab have been influential towards validating or disproving the accepted hypotheses for a catalyst’s mechanism. The research described below exemplifies the clarity the Blackmond lab has brought towards the characterization of the mechanism for two different C-H/arylation catalysts.

A catalyst can interact with many different molecules, including itself, during a chemical reaction. Catalysts that are capable of self-interaction are classified as multimeric, while those that cannot self-interact are deemed monomeric. The proper assignment of a catalyst as monomeric or multimeric can significantly change the working hypothesis for its mechanism. While investigating the mechanism of a chiral C-H/arylation catalyst, the Blackmond lab obtained experimental results that conflicted with previous reports by another research group, whose computer modeling studies had suggested the catalyst acted as both a monomeric and multimeric catalyst during the chemical reaction. However, the computation modeling was based upon the non-chiral version of the catalyst while the Blackmond lab was studying the chiral catalyst.

To experimentally verify the monomeric/multimeric nature of both the non-chiral and chiral catalysts, the Blackmond lab developed an experimental protocol that would allow the reaction itself to report on the monomeric/multimeric nature of the catalyst during the reaction conditions. This protocol, when applied to the non-chiral C-H/arylation catalyst, found the presence of both monomeric and multimeric catalysts, which held consistency with the previous computer modeling. The Blackmond lab then studied the chiral C-H/arylation catalyst with the protocol and found the sole presence of monomeric catalyst during the chemical reaction. These findings demonstrated that multimeric species may be present for one type of catalyst and play no role in another version, even for catalysts with similar chemical structure. This work serves as a caveat for those attempting to understand the mechanism of one catalyst by studying another. This protocol developed by the Blackmond lab represents a simple accessible method for understanding an important feature of a catalyst’s mechanism and will enable more chemists to simultaneously pursue mechanistic studies while developing new catalysts.

Author: David Hill

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