Direct Magnesiation of Polyfunctionalized Arenes and Heteroarenes Using (tmp)2Mg centre dot 2LiCl

摘要

Directed lithiations are important reactions for the function-alization of arenes and heterocycles. In contrast, directed magnesiation with magnesium bases has been used much less often. The pioneering work of Eaton et al. demonstrated the potential of this approach using magnesium bis(2,2,6,6-tetramethylpiperamide), (tmp)_2Mg. However, the limited solubility of such bases in common organic solvents as well as the requirement for an excess of the magnesium bases (2-7 equiv) to achieve high conversions has precluded their general use. Recently, we have reported that mixed Li/Mg amides of the type R_2NMgCl centre dot LiCl and in particular (tmp)MgCl centre dot LiCl (1) are highly soluble magnesium bases readily able to deprotonate a broad range of unsaturated substrates. However, some moderately activated arenes such as tert-butyl benzoate (2 a) gave unsatisfactory results (Scheme 1). Therefore, we have developed a new class of mixed Li/Mg bases: magnesium bisamides complexed with lithium chloride, (R2N)2Mg centre dot 2LiCl (3). The reagents 3a-c were readily prepared by reacting R2NLi with MgCl2 in THFat 0°C for 0.5 h. Whereas with (tmp)MgCl centre dot LiCl no significant deprotonation of 2 a was observed, the use of magnesium bisamides complexed with two equivalents of LiCl such as 3a-c led to excellent results (Scheme 1).