(tmp)2Zn2 MgCl22 LiCl: A Chemoselective Base for the Directed Zincation of Sensitive Arenes and Heteroarenes

摘要

The directed metalation of arenas and heteroarenes is an important method for the functionalization of these scaffolds. Lithium bases have been used extensively to ortho-metalate various unsaturated systems.[1] The use of magnesium bases pioneered by Eaton et al.[2] has recently found renewed interest.[3] There are a number of useful synthetic applications of lithium magnesiates[4], [5] as well as mixed Mg/Li bases of the type R2NMgClLiCl. (2,2,6,6-Tetramethylpiperidide)magnesium chloride-lithium chloride, (tmp)MgClLiCl (1), proved to be especially effective and is compatible with functional groups such as esters, nitriles, and aryl ketones.[6] More sensitive functionalities such as aldehydes and nitro groups are not tolerated. Also some classes of heterocycles, for example 1,3- and 1,2-oxazoles and 1,2,5- and 1,3,4-oxadiazoles, provide unstable lithiated or magnesiated intermediates, which are prone to ring opening.[7] Lithium di-tert-butyl-(2,2,6,6-tetramethylpiperidino)zincate, Li[tBu2(tmp)Zn], was reported by Kondo et al. to be an excellent base for the zincation of various arenes.[8] As highly reactive zincates or related ate bases[9] may not be compatible with aldehydes or nitro groups, we have explored the preparation of neutral zinc bases for the directed zincation of arenes and heteroarenes.