Abstract
Pd-catalyzed direct arylation of 2-alkylthiazoles is a well-known reaction affording
the corresponding 2-alkyl-5-arylthiazoles in very high yields. Conversely, the reactivity
of 2-alkoxythiazoles has not been described yet. Herein, we report conditions for
the Pd-catalyzed regioselective C5-arylation of 2-alkoxythiazoles. Moreover, we also
found reaction conditions leading to 3-alkyl-5-arylthiazol-2(3H )-ones via a one-pot direct arylation with an O - to N -alkyl migratory rearrangement. The judicious choice of reaction temperature and time
allows control over the selectivity of the reaction. In general, at 100 °C, 2-alkoxy-5-arylthiazoles
were the major products, whereas, at 120 °C with a longer reaction time, 3-alkyl-5-arylthiazol-2(3H )-ones were obtained with good selectivities. The arylation reaction is promoted by
a ligand-free air-stable palladium catalyst and a simple and inexpensive base, without
oxidant or further additives, and tolerates a variety of useful substituents on the
aryl bromide and also heteroaryl bromides.
Key words palladium catalysis - C–H functionalization - arylation - migratory rearrangement
- thiazoles - thiazolones
