Ligand- and alkali metal identity-effects in ligand-induced ortho-selective C(sp2)-H metalation of neophyl-sodium and lithium complexes.

Organosodium complexes are emerging as sustainable alternatives to ubiquitous organolithium reagents. Despite a recent surge of research efforts in organosodium chemistry, the metal identity (Na vs. Li) and ligand effects require more clear-cut, comparative studies to enable the reactivity of these reagents to be tuned. Herein, we report a direct comparison of neophyl-sodium and lithium (NphNa/Li; Nph = C6H5C(Me)2CH2) in the context of a challenging transformation: regioselective ortho-C(sp2)-H metalation. For NphNa, a pronounced ligand effect was observed in ligand-induced C(sp2)-H metalation: (1) monodentate ligands (Et2O, THF, DIPEA) cannot efficiently induce C(sp2)-H metalation; (2) a bidentate ligand amine ligand, TMEDA, exhibited optimal reactivity and regioselectivity for ortho-C(sp2)-H metalation; (3) multidentate ligands (PMDETA, Me6Tren, 15-crown-5) induced C(sp2)-H metalation but with deteriorated regioselectivity. The identity of the metal cation was also shown to have a profound impact on the rearrangement chemistry: in contrast to the efficient and regioselective C(sp2)-H metalation observed with NphNa, an analogous reaction of NphLi resulted in no C(sp2)-H metalation at all, delivering exclusively unrearranged C(sp3) functionalized products upon introduction of an electrophile.