Zinc reagents

In the presence of zinc dust (1.5−2.0 equiv) and LiCl (1.5−2.0 equiv), various benzylic chlorides bearing functional groups (iodide, cyanide, ester, ketone) are smoothly converted at 25 °C to the corresponding zinc reagents without homo-coupling (<5%). The utility of these benzylic zinc reagents is demonstrated by a short synthesis of papaverine.

• Metzger, Albrecht; Schade, Matthias A.; Knochel, Paul.    LiCl-Mediated Preparation of Highly Functionalized Benzylic Zinc Chlorides.    Org. Lett., 2008, 10, 1107-1110.

Treatment of (tmp)MgClLiCl (1) with ZnCl₂ (0.5 equiv, 25 °C, 15 h) provides (tmp)₂Zn2 MgCl₂2 LiCl (2). The resulting solution of the complex base has a high activity for the zincation of sensitive heterocycles such as 2-phenyl-1,3,4-oxadiazole (3) and N-tosyl-1,2,4-triazole (4).

• Wunderlich, Stefan H.; Knochel, Paul.    (tmp)₂Zn2 MgCl₂2 LiCl: A Chemoselective Base for the Directed Zincation of Sensitive Arenes and Heteroarenes.    Angew. Chem. Int Ed., 2007, 46, 7685-7688.

A wide range of polyfunctional aryl and heteroaryl zinc reagents were efficiently prepared in THF via direct zincation using (tmp)₂Zn·2MgCl₂·2LiCl and microwave irradiation. Ester and cyano functions as well as ketones are compatible with the high temperatures of the zincation. The resulting bis-organo zinc species undergo a number of subsequent reactions leading to highly functionalized aromatics and heteroaromatics in good to excellent yields.

• Wunderlich, Stefan H.; Knochel, Paul.    High Temperature Metalation of Functionalized Aromatics and Heteroaromatics using (tmp)₂Zn·2MgCl₂·2LiCl and Microwave Irradiation.    Org. Lett., 2008, 10, 4705–4707.

A wide range of polyfunctional aryl and heteroaryl zinc reagents were efficiently prepared in THF by using (TMP)₂Mg2 LiCl (TMP=2,2,6,6-tetramethylpiperamidyl) in the presence of ZnCl₂.

• Dong, Zhibing; Clososki, Giuliano C.; Wunderlich, Stefan H.; Unsinn, Andreas; Li, Jinshan; Knochel, Paul.    Direct Zincation of Functionalized Aromatics and Heterocycles by Using a Magnesium Base in the Presence of ZnCl₂.    Chem. Eur. J., 2008, 15, 457-468.

Benzylic zinc chlorides bearing various functional groups are smoothly prepared by the direct insertion of magnesium into benzylic chlorides in the presence of LiCl and ZnCl₂.

• Metzger, Albrecht; Piller, Fabian; Knochel, Paul    Polyfunctional benzylic zinc chlorides by the direct insertion of magnesium into benzylic chlorides in the presence of LiCl and ZnCl₂.    ChemComm, 2008, 5824 - 5826.