An experiment featuring an operationally simple Suzuki–Miyaura cross-coupling reaction suitable for a second-semester, second-year undergraduate organic chemistry laboratory course is presented. The cross-coupling reaction between 4-bromobenzoic acid and phenylboronic acid is run entirely in water and features an easily prepared and affordable palladium catalyst that requires no specialized equipment as the reaction can be run in a flask or beaker that is open to air. The product precipitates directly from the reaction mixture and is purified by a straightforward recrystallization from aqueous hydrochloric acid and ethanol. The cross-coupling reaction requires only 30 min of reaction time, allowing ample time to coordinate this reaction with other instructive exercises, such as recrystallization, melting point determination, and IR and NMR spectroscopy. The solvents used in the synthesis and purification provide a link to the growing commitment to sustainable chemistry in teaching laboratories and how safe, renewable solvents and catalysis play a role in green chemistry.

The Suzuki-Miyaura cross-coupling reaction is a foundation stone of modern organic synthesis, as evidenced by its widespread use in the preparation of pharmaceuticals, agrochemicals, polymers, and other functional materials. With the prevalence of this venerable reaction in industrial synthesis, it is prudent to ensure its application adheres to the tenets of green chemistry. The introduction of cross-coupling catalysts that are active in sustainable solvents is therefore an important endeavor. In this report, a melamine-palladium complex is introduced as a versatile catalyst for the Suzuki-Miyaura cross-coupling reaction. This catalyst is soluble and active in both water and the renewable organic solvent ethyl lactate. The melamine-palladium catalyst can also be cross-linked by reaction with formaldehyde to generate an insoluble polymeric catalyst that can be recovered after the cross-coupling. The melamine-palladium system is inexpensive, easy to handle, bench-stable, and effective in catalysis in the presence of a variety of impurities (high cross-coupling yields were obtained in reactions run in unfiltered river water to illustrate this final point). Additionally, investigations reported herein revealed an intriguing relationship between catalytic efficiency and the base employed in the cross-coupling reaction. Implications for the mechanism of transmetalation in aqueous Suzuki-Miyaura cross-coupling reaction are discussed.

The melamine/PdC(OAc) 2 catalyst is soluble and active in both water and the renewable nontoxic organic solvent ethyl lactate (ELA). Further, it is inexpensive, easy to handle, bench-stable, and effective in catalysis in the presence of a variety of impurities. The reaction of the catalyst with formaldehyde generates an insoluble polymeric catalyst that can be easily recovered and applied in Suzuki-Miyaura cross-coupling [reaction of (XII)]. -(EDWARDS, G. A.; TRAFFORD, M. A.; HAMILTON, A. E.; BUXTON, A. M.; BARDEAUX, M. C.; CHALKER*, J. M.; J. Org. Chem. 79 (2014) 5, 2094-2104, http://dx.