Curse or Blessing? Influence of Impurities on Cross-Coupling— Guideline for Elucidating Catalysts

Abstract

Several efforts have been made for the replacement of noble metal palladium in cross-coupling reactions, maintaining high efficiency of the target transformation. In several cases it is possible to perform the chemistry of palladium with related metals, and their activity was supported with mechanistic studies. Moreover, the complete exclusion of palladium is also in focus. Very recently it was demonstrated that special amine organocatalysts could catalyse Suzuki-Miyaura coupling reaction. Here we show that in this recent transformation homeopathic palladium impurities and trace phosphorous species originated from the conditions used for the organocatalyst synthesis are responsible for the catalytic effect instead of the amine species. This finding confirms the power of palladium in cross-coupling and draw the attention of impurity effect in this field of chemical research. In this article, we represent general guidelines for elucidating the real catalyst of reactions.<br>

Identifying palladium culprits in amine catalysis

“…During the preparation of this manuscript, a preprint was posted by Novák et al outlining complementary experiments that also demonstrate amine 1a is not catalytically active. 10…”

Amine-Catalysed Suzuki–Miyaura-Type Coupling? the Identification and Isolation of the Palladium Culprits.

“…During the preparation of this manuscript, a preprint was posted by Novák et al outlining complementary experiments that also demonstrate amine 1a is not catalytically active. 10…”

Pilot Study to Quantify Palladium Impurities in Lead-like Compounds Following Commonly Used Purification Techniques

“…In projects where there is a possibility of residual palladium interfering with biological assays or in subsequent reactions, measurement of the palladium content, and employment of palladium scavenging methods could minimise the potential for future problems. 67 − 73 …”

“…Accordingly, chemists cannot be certain that reaction products contain an acceptably low residual palladium level unless additional purification steps are routinely incorporated into synthetic practice or the more routine quantification of residual palladium levels is undertaken. In projects where there is a possibility of residual palladium interfering with biological assays or in subsequent reactions, measurement of the palladium content, and employment of palladium scavenging methods could minimise the potential for future problems. − …”