Solvent/base effects in the selective domino synthesis of phenanthridinones that involves high-valent palladium species: Experimental and theoretical studies

Abstract

The domino reaction of o-bromobenzamides 1-a-m in the presence of K 2CO 3 and the [PdCl 2(PPh 3) 2] catalyst granted a selective access to phenanthridinones 2 or to the new 1-carboxamide phenanthridinones 3 depending on the solvent, DMF or 1,4-dioxane, respectively. Investigations of the reaction parameters provided the first example of a direct correlation between the base dissociation and the solvent polarity on the selectivity observed. Moreover, mechanistic studies (NMR spectroscopy and ESI-MS monitoring) allowed us to characterize Pd II palladacycle 4 and biaryl species as common intermediates for these two domino processes. On that basis, C(sp 2)iC(sp 2) bond formation is envisaged by generation of a Pd IV complex after oxidative addition of 1 into Pd II palladacycle 4, a rationale that is supported by DFT calculations. A general catalytic cycle is proposed to account for these observations. Domino theory: The domino reaction of o-bromobenzamides 1 in the presence of K 2CO 3 and [PdCl 2(PPh 3) 2] granted a selective access to phenanthridinones 2 or to the new 1-carboxamide phenanthridinones 3 depending on the solvent (see scheme). Investigations showed a direct correlation between the base dissociation and the solvent polarity on the selectivity. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.