Direct C-H arylation of electron-deficient heterocycles with arylboronic acids

Abstract

A direct arylation of a variety of electron-deficient heterocycles with arylboronic acids has been developed. This new reaction proceeds readily at room temperature using inexpensive reagents: catalytic silver(I) nitrate in the presence of persulfate co-oxidant. The scope with respect to heterocycle and boronic acid coupling partner is broad, and sensitive functional groups are tolerated. This method allows for rapid access to a variety of arylated heterocycles that would be more difficult to access with traditional methods.

Figure 1

(A) Overview of the addition of arylboronic acids to electron-deficient heterocycles. (B) Initial findings with respect to arylboronic acid reactivity.

Figure 2

A mechanism consistent with previous studies by Minisci.

Scheme 1

Direct arylation of quinine.a ^a Quinine (0.125 mmol), arylboronic acid (0.25 + 0.125 mmol), TFA (0.375 mmol), AgNO₃ (0.025 mmol), K₂S₂O₈ (0.25 mmol), 23 °C, 3–24 h; isolated yield of chromatographically and spectroscopically pure product displayed.