A general, mild and efficient palladium-catalyzed 2,2,2-trifluoroethoxylation of activated aryl bromides and bromo-chalcones: bromo-chalcones a new coupling partner in cross-coupling reaction

Abstract

An efficient protocol for Pd-catalyzed 2,2,2-trifluoroethoxylation of activated aryl bromides and bromo-chalcones has been developed. We unveil a fascinating insight into the Pd-catalyzed C–O cross-coupling reaction. Pd/tBuXPhos (L1) ligand system facilitates the C–O cross-coupling reaction between 2,2,2-trifluoroethanol and activated aryl bromides at both higher (115 °C) and lower temperatures (40 °C). Unprecedentedly, this catalyst system facilitates the C–O cross-coupling reaction in short span of reaction times, generally 5–25 min (at 115 °C). The structurally simple analogue of tBuXPhos ligand so called JohnPhos (L2) ligand is also facilitated the C–O bond formation with activated aryl bromides and bromo-chalcones. Interestingly, under the optimal conditions (L1), methanol is also coupled rapidly with activated aryl bromides. These catalyst systems (L1 and L2) fail to couple electron rich aryl bromides with 2,2,2-trifluoroethanol, thus these catalyst systems allow the reductive elimination through an electronic pathway of reductive elimination. The unusual reactivity of 2,2,2-trifluoroethanol in Pd-catalyzed C–O cross-coupling reaction makes that the chemistry of fluorinated molecules is unique than that of non-fluorinated analogues. The bromo-chalcones can be used as a new coupling partner in the cross-coupling reaction.