Microwave irradiation, aryl chloride/bromide

Low reactive aryl chlorides are converted to the respective organomagnesium species in excellent yields through transition metal catalysis using 2 mol% FeCU (4-6, equation 3). Alternatively, a safe and reproducible method for activation of aryl chlorides or bromides 7 uses microwave irradiation (equation 4). In a synthesis of a novel HIV-1 protease inhibitor, microwave irradiation was essential to generate the starting arylmagnesium halide as well as to promote the subsequent Kumada coupling reaction. ... 

Leadbeater and Marco also undertook to optimise the reaction conditions for ligand-free Suzuki reactions in water using both aryl bromides and chlorides. Comparisons between reactions performed under microwave irradiation and oil-bath heating led to the conclusion that the yields were identical or better with oil baths when aryl bromides were used as aryl precursors. However, comparisons between microwave and oil-bath heating with aryl chlorides as starting material clearly favoured the microwave technique38. 

Rapid aminations of aryl chlorides and bromides using amine resins as the nitrogen nucleophile have been developed by Weigand and Pelka [120]. The normally very sluggish reaction (18 h, reflux) between the polystyrene Rink resin and electron-poor chlorides and bromides could be performed within 15 min under the action of microwave irradiation in a closed vessel (solvent DME-t-BuOH, 1 1) at 130 °C. This high-speed reaction was equally high yielding as the classic method. 

This reaction was modified by the replacement of CuCN with cheaper NaCN in the presence of palladium or nickel catalyst, as exemplified by the 5% Pd(PPh3)4/10% Cul catalyzed reaction and the Ni(CN)2 or NaCN/NiBr2 based reaction under microwave irradiation for aryl bromide. The latter condition is also used for the cyanation of aryl chloride with NaCN and NiBr2. In addition, this reaction has also been extended to the preparation of some Qf,)0-unsaturated nitriles. Further modifications include the copper-catalyzed domino halogen exchange-cyanation and the application of ionic liquid as reaction media. ... 

The use of less expensive aryl chlorides in this transformation has been reported using microwave irradiation [92]. Best results were obtained with Pfc-CgHiOs as ligand in combination with carbonate bases. Notably, under these conditions, phenylchloride proved to be more reactive than bromide or iodide (Scheme 37). 

Relatively unreactive aryl chlorides can be converted into the corresponding organomagnesium chlorides in excellent yields using transition metal catalysis with 2 mol% FeCU (5-7 Scheme 2-12 eq. (a)) " Another safe and reproducible method for aryl chlorides or bromides activation uses iodine and microwave irradiation (Scheme 2-12 eq. (b)), leading to the Grignard reagents of type 8 in 61-99%. ... 

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