Stretchable chiral pockets for palladium-catalyzed highly chemo- and enantioselective allenylation

Abstract

Pyrazolones are a vital class of heterocycles possessing various biological properties and much attention is paid to the diversified synthesis of enantiopure pyrazolone derivatives. We describe here the development of diphenylphosphinoalkanoic acid based chiral bisphosphine ligands, which are successfully applied to the palladium-catalyzed asymmetric allenylation of racemic pyrazol-5-ones. The reaction affords C-allenylation products, optically active pyrazol-5-ones bearing an allene unit, in high chemo- and enantioselectivity, with DACH-ZYC-Phos-C1 as the best ligand. The synthetic potential of the C-allenylation products is demonstrated. Furthermore, the enantioselectivity observed with DACH-ZYC-Phos-C1 is rationalized by density functional theory studies.

Chiral pyrazolone derivatives show promising biological activity in commercial drugs. Here, the authors report an enantioselective allenylation of pyrazolones by fine tuning of Trost’s ligands, which leads to a chiral pocket featuring high efficiency and asymmetric induction in the catalytic process.