DOE OSTI · 3023783
Bulky Phosphine Ligands Promote Palladium-Catalyzed Protodeboronation
Abstract
The Suzuki-Miyaura cross-coupling reaction is plagued by protodeboronation, an undesirable side reaction with water that consumes the boronic acid derivatives required for the cross-coupling reaction. Meticulous mechanistic studies have previously established protodeboronation to be highly sensitive to the nature of the boronic reagent and reaction conditions. Particularly, the presence of bases, which are essential for the Suzuki-Miyaura coupling, is known to catalyze protodeboronation. However, protodeboronation catalyzed by palladium-phosphine complexes, the benchmark catalyst system for Suzuki-Miyaura cross-coupling, has been understudied compared to its base-catalyzed counterpart. Here, we demonstrate, using automated high-throughput experimentation, comprehensive computational mechanistic analyses and kinetic modeling, that protodeboronation is accelerated by palladium(II) complexes bound to bulky phosphine ligands. While sterically hindered ligands are typically used to facilitate difficult cross-couplings, these ligands can instead paradoxically impede cross-coupling product formation, requiring careful and judicious consideration when choosing ligands for Suzuki-Miyaura cross-couplings.
Keep this discovery
Explore connections, maps & timelines
Ser, Cher Tian [University of Toronto, ON (Canada); Vector Institute for Artificial Intelligence, Toronto, ON (Canada)] (ORCID:0000000305975758), Hao, Han [University of Toronto, ON (Canada); Acceleration Consortium, Toronto, ON (Canada)], Pablo-García, Sergio [University of Toronto, ON (Canada); Vector Institute for Artificial Intelligence, Toronto, ON (Canada); Acceleration Consortium, Toronto, ON (Canada)] (ORCID:0000000233279285), Jorner, Kjell [University of Toronto, ON (Canada); ETH Zurich (Switzerland)] (ORCID:0000000241916790), Li, Shangyu [University of Toronto, ON (Canada); Harvard University, Cambridge, MA (United States)] (ORCID:0009000998201997), Pollice, Robert [University of Toronto, ON (Canada); University of Groningen (The Netherlands)] (ORCID:0000000188366266), Aspuru-Guzik, Alán [University of Toronto, ON (Canada); Vector Institute for Artificial Intelligence, Toronto, ON (Canada); Acceleration Consortium, Toronto, ON (Canada); Canadian Institute for Advanced Research (CIFAR), Toronto, ON (Canada); Institute of Medical Science, Toronto, ON (Canada)] (ORCID:0000000282774434). 2025-11-17. Bulky Phosphine Ligands Promote Palladium-Catalyzed Protodeboronation. https://doi.org/10.1021/jacs.5c14153
Cite the original work for its findings. Save a collection to share your selection of sources.