These are preliminary reports that have not been peer-reviewed. They should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information. For more information, please see our FAQs.
Preprints are manuscripts made publicly available before they have been submitted for formal peer review and publication. They might contain new research findings or data. Preprints can be a draft or final version of an author's research but must not have been accepted for publication at the time of submission.
The ability to use soluble organic amine bases in
Pd-catalyzed C–N cross-coupling reactions has provided a long-awaited solution
to the many issues associated with employing traditional, heterogeneous
reaction conditions. However, little is known about the precise function of
these bases in the catalytic cycle and about the effect of variations in base
structure on catalyst reactivity. We used 19F NMR to analyze the
kinetic behavior of C–N coupling reactions facilitated by different organic
bases. In the case of aniline coupling reactions employing DBU, the resting
state was a DBU-bound oxidative addition complex, LPd(DBU)(Ar)X, and the reaction
was found to be inhibited by base. In general, however, depending on the binding
properties of the chosen organic base, increased concentration of the base can
have a positive or negative influence on the reaction rate. We propose a model
in which the turnover-limiting step of the catalytic cycle depends on the
relative nucleophilicity of the base compared to that of the amine. This
hypothesis guided the discovery of new reaction conditions for the coupling of
weakly binding amines, including secondary aryl amines, which were unreactive
nucleophiles in our original protocol.