Iron-catalyzed cross-coupling of arylboronic acids with unactivated N-heterocycles and quinones under microwave heating

Start, Keegan (2019) Iron-catalyzed cross-coupling of arylboronic acids with unactivated N-heterocycles and quinones under microwave heating. Masters thesis, Memorial University of Newfoundland.

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Abstract

Traditional C-C cross-coupling reactions generally rely on the use of expensive and sometimes toxic metal catalysts, such as palladium or ruthenium. These methods generally require two functionalized reagents, which can increase reaction cost. In the interests of sustainability and reduced costs there has been considerable interest in catalysis using earth-abundant metals, such as iron, as well as in C-H activation reactions. One example of a C-H activation reaction is the Minisci reaction, which is a radical reaction that couples N-heteroarenes to a variety of organic species. Recently a variation of the Minisci reaction was discovered in which arylboronic acids, which are relatively cheap and easily available, are coupled to N-heteroarenes or quinones using either a silver or iron catalyst. This process occurs under air and at low temperatures, but requires long reaction times, has a somewhat limited scope, and is not regioselective. This thesis concerns the application of microwave heating to this reaction, in an attempt to mitigate these issues. Microwave heating has not been previously applied to the Minisci reaction, and in fact there are relatively few reports on radical reactions under microwave heating. The reaction between pyrazine and arylboronic acids under microwave heating was first optimized. Ultimately, optimization led to similar product yields, but reactions that previously required 12 — 48 h could be conducted in 25 min. The reaction scope was then examined. The scope of arylboronic acids when reacted with pyrazine was somewhat limited, as strong electron-withdrawing and electron-donating groups were not tolerated. Examination of the reaction mixtures revealed that two previously unobserved side reaction were taking place; first, a reaction in which the boronic acid moiety was replaced by a hydroxyl group, and second, N-heteroarene homo-coupling. The reaction scope with quinones was found to be similar to literature reports, but reactions still occurred at a much higher rate. The reaction was successfully extended to hydroquinones, but attempts to further expand scope to enones, imines, and other conjugated compounds were unsuccessful. Finally, the scope of reactions with N-heteroarenes was examined and was found to be similar to literature reports. The application of microwave heating did not significantly affect the regiochemical outcomes of the reaction.

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