Graduate Student Lydia Yorks

"The Role of Various Salts Impacting the Reactivity of Organozinc Reagents"

The effect of salt additives on the general reactivity of organozinc reagents is only recently appreciated.[1] The organozinc reagent is a key coupling partner with an organic halide in the transmetalation step of the Negishi reaction.[2] By analysis of single-metal-particle fluorescence microscopy and proton NMR spectroscopy, the effects of varying lithium salts on the development of soluble intermediates on the surface of the zinc was revealed.[1] For instance, lithium bromide (and other salts) is produced via the Rieke protocol, and while they were previously thought to have no impact on the catalytic reaction, studies have shown that they are necessary to prevent catalyst death by prevention of an undesirable beta-hydride elimination reaction.[3] The reactivity control was found to be dictated by the salts present in the supernatant instead of the salts present in the solid.[4] By altering the salt complex presence in the supernatant, or by keeping or removing the supernatant, the reaction kinetics and structure of the organozinc product can be altered. The need for the supernatant was discovered via use of fluorescence microscopy with single-Rieke-zinc particle resolution, inductively coupled plasma- mass spectrometry, X-ray photoelectron spectroscopy, energy dispersive spectroscopy, and scanning electron microscopy.[4] These findings simplify the synthetic manipulation of organozinc reactivity by adding a soluble salt to the solutions used in preparation of the metal reagents instead of trying to alter the composition and lattice structure of the reagent.[4]

References:

(1) Jess, K.; Kitagawa, K.; Tagawa, T. K. S.; Blum, S. A. Microscopy Reveals: Impact of Lithium Salts on Elementary Steps Predicts Organozinc Reagent Synthesis and Structure. J. Am. Chem. Soc. 2019, 141, 9879–9884.
(2) Baba, S.; Negishi, E.1976. A novel stereospecific alkenyl-alkenyl cross-coupling by a palladium-or nickel-catalyzed reaction of alkenylalanes with alkenyl halides. J. Am. Chem. Soc. 1976, 98 (21), 6729-6731.
(3) P. Eckert, M.G. Organ. A Path to More Sustainable Catalysis: The Critical Role of LiBr in Avoiding Catalyst Death and Its Impact on Cross‐Coupling.
Chem. Eur. J. 2020, 26, 4861-4865.
(4) Hanada, E. M.; Tagawa, T. K. S.; Kawada, M.; Blum, S. A. Reactivity Differences of Rieke Zinc Arise Primarily from Salts in the Supernatant, not in the Solids. J. Am. Chem. Soc. 2022, 144, 12081–12091.