2 research outputs found
Completely N<sup>1</sup>-Selective Palladium-Catalyzed Arylation of Unsymmetric Imidazoles: Application to the Synthesis of Nilotinib
The completely N<sup>1</sup>-selective Pd-catalyzed arylation
of
unsymmetric imidazoles with aryl halides and triflates is described.
This study showed that imidazoles have a strong inhibitory effect
on the in situ formation of the catalytically active Pd(0)–ligand
complex. The efficacy of the N-arylation reaction was improved drastically
by the use of a preactivated solution of Pd<sub>2</sub>(dba)<sub>3</sub> and <b>L1</b>. From these findings, it is clear that while
imidazoles can prevent binding of <b>L1</b> to Pd, once the
ligand is bound to the metal, these heterocycles do not displace it.
The utility of the present catalytic system was demonstrated by the
regioselective synthesis of the clinically important tyrosine kinase
inhibitor nilotinib
Me<sub>3</sub>(OMe)<i>t</i>BuXPhos: A Surrogate Ligand for Me<sub>4</sub><i>t</i>BuXPhos in Palladium-Catalyzed C–N and C–O Bond-Forming Reactions
A new biarylphosphine ligand, Me<sub>3</sub>(OMe)<i>t</i>BuXPhos (<b>L3</b>), was designed as a surrogate
for Me<sub>4</sub><i>t</i>BuXPhos (<b>L1</b>). The
Me<sub>3</sub>(OMe)<i>t</i>BuXPhos could be prepared in
a chromatography-free manner from inexpensive and readily available
2,3,6-trimethylphenol. Comparative studies demonstrated that a catalyst
based on Me<sub>3</sub>(OMe)<i>t</i>BuXPhos displayed the
same reactivity as a catalyst based on Me<sub>4</sub><i>t</i>BuXPhos for Pd-catalyzed C–N and C–O bond-forming processes