Synthesis of Amidines by Palladium-Mediated CO2 Extrusion Followed by Insertion of Carbodiimides: Translating Mechanistic Studies to Develop a One-Pot Method

A palladium-mediated one-pot synthesis of amidines from aromatic carboxylic acids and carbodiimides (RNCNR) is reported as an isoelectronic adaption of CO2ExIn (ExIn = Extrusion–Insertion) reactions developed for the synthesis of thioamides from carboxylic acids and isothiocyanates (RNCS). Multistage mass spectrometry (MSn) experiments for model systems established “proof of concept”, demonstrating decarboxylation of [(L)Pd(O2CAr)]+ (L = 1,10-phenanthroline or py), to give [(L)PdAr]+, followed by reaction with a carbodiimide, RNCNR, to yield [(L)Pd(NRC(NR)Ar)]+ (R = isopropyl). DFT calculations predicted these reactions as highly exothermic and occurring via carbodiimide insertion into the Pd–Ph bond. 2,6-Dimethoxy and 2,4,6-trimethoxy substitution for the Pd–Ar moiety results in slower reactions with minor changes in mechanism. The individual reaction steps associated with the conversion of 2,6-dimethoxybenzoic acid and 2,4,6-trimethoxybenzoic acid into amidines in solution was probed by 1H NMR spectrosc...