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. 2012 May 7;51(19):4710-3.
doi: 10.1002/anie.201201244. Epub 2012 Mar 30.

A bulky biaryl phosphine ligand allows for palladium-catalyzed amidation of five-membered heterocycles as electrophiles

Mingjuan Su  1 , Stephen L Buchwald
Affiliations

A bulky biaryl phosphine ligand allows for palladium-catalyzed amidation of five-membered heterocycles as electrophiles

Mingjuan Su et al. Angew Chem Int Ed Engl. .

Abstract

Palladium-catalyzed amidation of five-membered heterocyclic bromides that contain multiple heteroatoms was achieved for the first time using the Pd/1 catalyst system. This system allows for efficient access to N-arylated imidazoles, pyrazoles, thiazoles, pyrroles, and thiophenes in moderate to excellent yield. Experimental results and DFT calculations point to the need for electron-rich and especially sterically demanding biaryl phosphine ligand to promote these difficult cross-coupling reactions.

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Figures

Figure 1
Figure 1
Synthesis and X-ray structures of oxidative addition complexes (where L3 = tBuBrettPhos and L6 = AdBrettPhos). Thermal ellipsoid plot at 50% probability; hydrogen atoms omitted for clarity.
Figure 2
Figure 2
Optimized ground state structures for monoligated LPd(HetAr)(benzamidate) complexes (phosphorus in orange, palladium in green, nitrogen in blue, oxygen in red). Hydrogen atoms omitted for clarity. Angle P–Pd–C1: (A, 97.0°; B, 97.7°; C, 98.5°)
See this image and copyright information in PMC

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