The copper catalysed reaction of unactivated aryl bromides with sodium methoxide has been investigated by studying a number of parameters (copper catalyst, cosolvent, concentration and relative ratio of the reactants, additives and aryl bromide substituents) which influence this reaction. 'Die ipso-substitution reaction was found to proceed via an intimate electron transfer mechanism involving a cuprate-like intermediate, Na[Cu(OMe)2]. A convenient synthesis of methyl aryl ethers from sryl bromides and concentrated sodium methoxide solutions in dimethyl formami de and methanol is presented. Also an attempt to extend this reaction to the use of chlorine derivatives was made.

High throughput screening was used to find a cost-effective and scalable catalyst for the asymmetric hydrogenation of a sterically demanding enamide as an intermediate towards a new potent melanocortin receptor agonist useful in the treatment of obesity. Lessons drawn from the testing of a first library of 96 chiral monodentate phosphoramidites led to the design of a second focused library of 16 chiral ligands, allowing the discovery of a new efficient catalyst. This catalyst was based on rhodium and a bulky monodentate phosphite ligand. The catalyst was scaled up and used in the kilogram production of the desired bulky chiral amide.

ChemInform Abstract The title reaction is extensively studied a) to develop a convenient synthesis of methyl aryl ethers from aryl bromides, b) to elucidate the mechanism, and c) to extend eventually this reaction to aryl chlorides (yielding the environmentally favored NaCl as the waste product instead of NaBr). The reaction parameters are widely varied, e.g., 1. cat. (age unimportant, non-linear increase in reaction rate with increasing concentration), 2. cosolvent (only DMF has a positive effect), 3. concentration of NaOMe (II) (very important) and Br-(reaction is retarded), and 4. substituents (Hammett correlation). With Ph-Cl as the substrate, reduction takes place (formation of benzene) instead of substitution.