Direct metalation of methoxymethyl arylmethyl ethers: A tin-free approach to the generation of α-alkoxyalkoxy-substituted aryllithiums

The generation of a series of α-methoxymethoxy-substituted arylmethyllithiums was achieved by direct metalation of the corresponding arylmethyl methoxymethyl ethers. While the effect of substituents at the benzylic position is straightforward, substituents located on the aromatic ring promote the set up of a competition between lateral and aromatic metalation, strongly affected by the position and relative ortho directing properties of the new substituent. The proposed methodology allows a simple approach to the generation of a wide array of functionalized organolithium reagents.

Graphical abstractA wide array of α-methoxymethoxy-substituted arylmethyllithiums was generated by direct metalation of the corresponding arylmethyl methoxymethyl ethers, thus avoiding manipulation and isolation of toxic organotin reagents. Substituents located on the aromatic ring promote the set up of a competition between lateral and aromatic metalation.Figure optionsDownload full-size imageDownload as PowerPoint slide