Suzuki-Miyaura coupling optimal reaction conditions

Our group recently reported the development of a coumarin library with diversity at the 6-position via Suzuki-Miyaura coupling.21 The reaction conditions were optimized for the reaction of the 6-bromocoumarin scaffold 9 with the unsubstituted phenyl boronic acid pinacol ester 10a (Figs. 18.6 and 18.7). 

The development of catalytic systems using neat water as solvent is of high importance to industrial and environmentally friendly applications. In this respect, water is perhaps the ultimate solvent because of its lack of toxicity and ready availability. Leadbeater has published several papers where the Suzuki-Miyaura reaction has been optimized for aqueous conditions [9,120]. Aryl bromides and iodides were coupled and the corresponding products isolated in good yields with an attractive ligandless protocol. Some reactions gave increased yields with the addition of tetrabutylammonium bromide (TBAB) [121], Recently, an application for a scaled-up Suzuki-Miyaura synthesis in water using an automated batch stop-flow apparatus was also published (Scheme 46) [89]. 

Additionally, Suzuki-Miyaura cross coupling reactions can be performed on similar supported iodides. Aryl bromides could be employed in this reaction as well. After optimization of conditions, it turned out that a hydroxyl-derived IL was the best solvent for this reaction. Namely, reaction completion was obtained after 12 h at room temperature in [N11130H][NTf2] in the presence of 1% Pd(OAc)2 and using potassium carbonate as abase. Under these conditions, less than 1% of homocoupling product is observed and easily eliminated by washing with diethyl ether prior to transesterification with methanol. Overall, biphenyls were isolated under analytically pure form in 90-95% yields [126],... 

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