Identification of a Surprising Boronic Acid Homocoupling Process in Suzuki-Miyaura Cross-Coupling Reactions Utilizing a Hindered Fluorinated Arene

The Suzuki-Miyaura cross-coupling reaction of 2-bromo-1,3-bis(trifluoromethyl)benzene with arylboronic acids was evaluated and determined to suffer from the formation of large amounts of boronic acid homocoupling products in conjunction with dehalogenation. Homocoupling product formation in this process likely occurs through a rare protonolysis/second transmetalation event rather than by the well-established mechanism requiring the involvement of O-2. The scope of this boronic acid homocoupling reaction was investigated and shown to predominate with electron-deficient arylboronic acids. Finally, a good yield of cross-coupling products could be obtained by employing dicyclohexyl(2 ',6 '-dimethoxybiphenyl-2-yl)phosphine (SPhos) as the ligand.

Automated summary

The Suzuki-Miyaura cross-coupling reaction of 2-bromo-1,3-bis(trifluoromethyl)benzene with arylboronic acids leads to the formation of significant amounts of boronic acid homocoupling products, especially with electron-deficient arylboronic acids. Good yields of cross-coupling products can be achieved by utilizing dicyclohexyl(2',6'-dimethoxybiphenyl-2-yl)phosphine (SPhos) as the ligand.