4-Arylation of N-Acylamino- and Aminopyrazoles by the Suzuki-Miyaura Cross-Coupling Reaction

Halogenated aminopyrazoles have rarely been utilized in metal‐catalysed cross‐coupling reactions mainly due to the complexation of the aminopyrazoles to the metal center, which deactivates the catalyst. In this paper we reveal that the appropriate combination of palladium source and ligand enables efficient Suzuki–Miyaura cross‐coupling reactions with even challenging substrates such as halogenated aminopyrazoles. The combination of Pd(OAc)2 and XPhos allowed efficient coupling of halogenated N‐acetylaminopyrazoles, whereas XPhos Pd G2 was needed when unprotected aminopyrazoles were used. Generally, the halogenated aminopyrazoles underwent facile cross‐coupling reactions with a range of aryl‐, heteroaryl‐, and styrylboronic acids and esters. The resulting biaryl, bisheteroaryl, or arylalkenyl derivatives were obtained in good‐to‐high isolated yields. Halogenated pyrazoles containing an amino group have rarely been used as reagents in metal‐catalyzed cross‐couplings due to the complexation of aminopyrazoles to the metal, resulting in inhibition of the catalyst. We reveal herein that the appropriate combination of Pd source and ligand enables efficient Suzuki–Miyaura cross‐couplings with challenging substrates such as halogenated aminopyrazoles.