Diazonium Salts
Since halo-organics are often manufactured from the corresponding amine, via diazonium chemistry and Sandmeyer reactions, it would seem sensible to try to use the diazonium salts in reaction instead of the halides. Older chemists will remember the copper catalysed Meerwein reaction (addition of RN2+ X- across an unsaturated ketone double bond with loss of nitrogen) which does not give great yields unless you substitute acetonitrile for acetone in the old recipes.
At the Prague conference, Prof Bernd Schmidt (Univ of Potsdam) and Dr Francois-Xavier Felpin (Univ of Bordeaux) both gave excellent presentations on the use of the palladium catalysed reactions of diazonium salts with olefins, and both mentioned that this reaction is already used in the manufacture of the Syngenta herbicide Prosufuron on multi-tonne scale.
Whilst the details are too numerous to mention, in the Schmidt talk he mentioned the use of phenolic diazonium tetrafluoroborates and that they can be used without any OH protection ( possibly existing as stable quinonediazides?), and they can be added to styrenes, unsaturated carbonyls and vinyl ethers as well as used in cross coupling reactions to give biaryls, using simple palladium acetate as catalyst at room temperature, conditions which are process friendly. The diazonium salts can be prepared directly from protected amines (eg amides) by a combined deacetylation/diazotisation sequence, eg from paracetamol.
Dr Felpin focussed on use of Pd/C as a heterogeneous catalyst for similar reactions of diazonium salts involving C-C bond formation, followed by use of the catalyst for subsequent reactions (eg hydrogenation of the double bond or deprotection). The Pd/C could even be made in house from palladium acetate and charcoal followed by hydrogenation.
Yields in these reactions were as high as 98% with catalyst loadings as low as 0.005%. Both groups have patented their procedures, however.
To emphsise the utility of these reactions a third speaker, Kai Rossen of Sanofi Aventis had used the Heck diazonium reaction to make a key intermediate in a drug synthesis from a Baylis-Hillman adduct.
