Suzuki-Miyaura coupling solvents

Example 5, Nickel-catalyzed Suzuki-Miyaura coupling in green solvents ... 

Along with their work on the nickel-catalyzed Suzuki-Miyaura coupling of neopentylglycol boronic esters, Percec and coworkers examined the speed of transesterification of a cyclic arylboronic ester with a diol under anhydrous conditions. In both assays in Scheme 3.2, some transesterification had taken place after 10 h (equilibrium was not reached). This result shows that transesterification of cyclic boronic esters is always possible, even starting from pinacol esters. This should be kept in mind when considering reactions in the presence of alcohol solvents and water. 

Heterogeneous Pd catalysts can activate the C-Cl bond in aryl chlorides for the Suzuki-Miyaura reaction, presumably due to a synergistic anchimeric and electronic effect that occurs between the Pd surface and the aryl chlorides. Pd on carbon has been found to be a very effective pre-catalyst for a variety of substrates even under very mild reaction conditions and aqueous solvent mixtures.In 2001, Kabalka and co-workers described that Pd powder and KF as base were useful to couple aryl iodides with arylboronic acids in methanol." At the conclusion of the reaction, Pd metal could be recovered by simple decantation. The use of microwave irradiation accelerates the reaction by... 

It is noteworthy that the microwave-assisted Suzuki-Miyaura reactions were found to be far superior to the reactions under conventional heating, as can be demonstrated by yield improvements from 22% to 84% in the case of cross-coupling of PEA derivatives. Microwave-irradiation also provided smooth conversions in water as the sole solvent. 

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]. 

Fig. 12.7 Examples of Suzuki-Miyaura cross-couplings yielding chromophore-modified DNA bases. THF-MeOH-H20 was used as the solvent and NaOH as the base.

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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