[Pd(NHC)(μ-Cl)Cl]2: Versatile and Highly Reactive Complexes for Cross-Coupling Reactions that Avoid Formation of Inactive Pd(I) Off-Cycle Products

Zhou, Tongliang; Ma, Siyue; Nahra, Fady; Obled, Alan M.C.; Poater, Albert; Cavallo, Luigi; Cazin, Catherine S.J.; Nolan, Steven P.; Szostak, Michal

doi:10.1016/j.isci.2020.101377

The cross-coupling of aryl esters has emerged as a powerful platform for the functionalization of otherwise inert acyl C–O bonds in chemical synthesis and catalysis. Herein, we report a combined experimental and computational study on the acyl Suzuki–Miyaura cross-coupling of aryl esters mediated by well-defined, air- and moisture-stable Pd( ii )–NHC precatalysts [Pd(NHC)(μ-Cl)Cl] 2 . We present a comprehensive evaluation of [Pd(NHC)(μ-Cl)Cl] 2 precatalysts and compare them with the present state-of-the-art [(Pd(NHC)allyl] precatalysts bearing allyl-type throw-away ligands. Most importantly, the study reveals [Pd(NHC)(μ-Cl)Cl] 2 as the most reactive precatalysts discovered to date in this reactivity manifold. The unique synthetic utility of this unconventional O–C(O) cross-coupling is highlighted in the late-stage functionalization of pharmaceuticals and sequential chemoselective cross-coupling, providing access to valuable ketone products by a catalytic mechanism involving Pd insertion into the aryl ester bond. Furthermore, we present a comprehensive study of the catalytic cycle by DFT methods. Considering the clear advantages of [Pd(NHC)(μ-Cl)Cl] 2 precatalysts on several levels, including facile one-pot synthesis, superior atom-economic profile to all other Pd( ii )–NHC catalysts, and versatile reactivity, these should be considered as the ‘first-choice’ catalysts for all routine applications in ester O–C(O) bond activation.

More Like this