On novel non-organometallic aryl nucleophile in palladium-catalyzed arylation

The arylation of aromatic electrophiles (halogenoaromatics, triflates, diazonium) catalyzed by palladium is known with numerous organometallic aryl nucleophiles of boron (Suzuki-Miyaura), silicon(Hiyama), tin(Stille), zinc (Negishi), mercury (Heck)... which obviously leads to sub -products containing metals. If boron and silicon are only slightly or not toxic, a large majority of metals present a toxicity which can be annoying during the synthesis of molecules for therapeutic purposes. This is particularly the case for tin in the Stille reaction.

We investigated whether it was not possible to use a non-organometallic phenyl anion derived from an elimination reaction as a nucleophilic arylation agent. Tests using a carboxylate or a sulfinate were not successful, on the other hand phenylazocarboxylate led to interesting results. Phenylazacarboxylate was introduced by Nesmeyanov (1948) in the synthesis of arylmercury componds. This compound was not reused, however, and was never tested in catalyzed palladium couplings, unknown at that time. During phenylation, one molecule of nitrogen and one molecule of carbon dioxide are removed.The precursor of phenylazocarboxylate is commercially available 1-phenylsemicarbazide, its oxidation gave of 1-phenyldiazocarboxamide.We obtained potassium phenylazacarboxylate by saponification with potash of 1-phenyldiazocarboxamide under ultrasound irradiation, without heating, in a yield of 81%.

A water-dioxane mixture with a water soluble palladium complexe was used under microwave irradiation with the potassium phenylazocarboxylate. It therefore appears that arylazocarboxylates can be non-organometallic arylnucleophiles in aromatic arylations.