A convenient alumination of functionalized aromatics by using the frustrated Lewis pair Et3 Al and TMPMgCl⋅LiCl.

A straightforward and efficient alumination of functionalized arenes by using the frustrated Lewis pair Et3 Al and TMPMgCl⋅LiCl (TMP=2,2,6,6-tetramethylpiperidyl) has been developed. In particular, halogenated electron-rich aromatics can be smoothly functionalized by using the frustrated Lewis pair Et3 Al and TMPMgCl⋅LiCl. Compared with previously described alumination methods, this procedure avoids extensive cooling and the need for an excess of base.

Aluminum bases for the highly chemoselective preparation of aryl and heteroaryl aluminum compounds.

Selective C-H activation with a series of neutral aluminum trisamide bases led to a wide range of polyfunctional aryl and heteroaryl aluminum reagents. Ester and cyano groups are stable under the reaction conditions for this direct alumination, and donor oxygen substituents are efficient directing groups. High metalation regioselectivities were observed with O,S and N,S heterocycles (see example).

Efficient mono- and bis-functionalization of 3,6-dichloropyridazine using (tmp)2Zn.2MgCl2.2LiCl.

3,6-Dichloropyridazine undergoes a smooth metallation using (tmp)2Zn.2MgCl2.2LiCl.

Direct zincation of functionalized aromatics and heterocycles by using a magnesium base in the presence of ZnCl2.

A wide range of polyfunctional aryl and heteroaryl zinc reagents were efficiently prepared in THF by using (TMP)(2)Mg2 LiCl (TMP=2,2,6,6-tetramethylpiperamidyl) in the presence of ZnCl(2). The possible pathways of this metalation procedure as well as possible reactive intermediates are discussed. This experimental protocol expands the tolerance of functional groups and allows an efficient zincation of sensitive heterocycles such as quinoxaline or pyrazine.

High temperature metalation of functionalized aromatics and heteroaromatics using (tmp)2Zn x 2 MgCl2 x 2 LiCl and microwave irradiation.

A wide range of polyfunctional aryl and heteroaryl zinc reagents were efficiently prepared in THF via direct zincation using (tmp)2Zn x 2 MgCl2 x 2 LiCl 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.

Halogen-magnesium exchange on unprotected aromatic and heteroaromatic carboxylic acids.

The magnesiation of halogenated aromatic and heteroaromatic carboxylic acids is accomplished by their treatment with MeMgCl in the presence of LiCl and subsequent reaction with i-PrMgCl.LiCl; the resulting double-magnesiated species react with a variety of electrophiles in up to 97% yield.