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. 2014 Aug 15;16(16):4296-9.
doi: 10.1021/ol502014b. Epub 2014 Aug 4.

Mild Pd-catalyzed aminocarbonylation of (hetero)aryl bromides with a palladacycle precatalyst

Stig D Friis  1 , Troels Skrydstrup, Stephen L Buchwald
Affiliations

Mild Pd-catalyzed aminocarbonylation of (hetero)aryl bromides with a palladacycle precatalyst

Stig D Friis et al. Org Lett. .

Abstract

A palladacyclic precatalyst is employed to cleanly generate a highly active XantPhos-ligated Pd-catalyst. Its use in low temperature aminocarbonylations of (hetero)aryl bromides provides access to a range of challenging products in good to excellent yields with low catalyst loading and only a slight excess of CO. Some products are unattainable by traditional carbonylative coupling.

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Figures

Figure 1
Figure 1
Selection of FDA-approved drugs containing heteroaryl amides.
Figure 2
Figure 2
Palladacycle precatalyst and phosphine ligands examined for low temperature aminocarbonylations.
Scheme 1
Scheme 1. Low Temperature Aminocarbonylation of (Hetero)Aryl Bromides with Morpholine; Isolated Yields and Average of Two Runs, (Het)Ar–Br (1.0 mmol), 0.50 M
Used as HCl salt, Et3N (3.0 mmol). 80 °C. 65 °C. MePh2SiCO2H (1.0 mmol), KF (1.0 mmol). 2,4-Dibromothiazole (0.5 mmol). 0.25 M.
Scheme 2
Scheme 2. Low Temperature Aminocarbonylation of 2-Bromopyridine and a Selection of Amines; Isolated Yields and Average of Two Runs, 2-Bromopyridine (1.0 mmol), 0.50 M
65 °C. Et3N (4.0 mmol). Used as HCl ammonium salt. 0.25 M. RR′NH (1.2 mmol), Et3N (3.2 mmol).
Figure 3
Figure 3
Comparison of palladacycle precatalyst 1f with traditional Pd sources at different temperatures. GC yields, 2 (1.0 mmol), 0.50 M.
See this image and copyright information in PMC

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