Synthesis of unsymmetrically substituted biaryls via sequential lithiation of dibromobiaryls using integrated microflow systems

• Aiichiro Nagaki,
• Naofumi Takabayashi,
• Yutaka Tomida and
• Jun-ichi Yoshida

Beilstein J. Org. Chem. 2009, 5, No. 16, doi:10.3762/bjoc.5.16

• micromixers and four microtube reactors to obtain unsymmetrically substituted biaryl compounds. Keywords: dibromobiaryls; fast mixing; integrated microflow system; selective lithiation; unsymmetrically substituted biaryls; Introduction Unsymmetrical biaryls have received significant research interest

• biaryls [2][3][4][5][6][7][8][9]. Selective monolithiation of dihalobiaryls also seems to be useful for synthesis of unsymmetrically substituted biaryls because the remaining halogen atom can be utilized for further transformations [10][11][12]. However, halogen-lithium exchange reactions of dihalobiaryls

• ][53]. Recently, we reported that selective monolithiation can be achieved by extremely fast 1:1 micromixing of dibromobiaryls and n-butyllithium using microflow systems [54]. The successful results prompted us to perform a study on the synthesis of unsymmetrically substituted biaryls via sequential