Toward a Better Understanding on the Mechanism of Ortholithiation. Tuning of Selectivities in the Metalation of meta-Anisic Acid by an Appropriate Choice of Base
Thi-Huu Nguyen, Nguyet Trang Thanh Chau, Anne-Sophie Castanet, Kim Phi Phung Nguyen, and Jacques Mortier
Org. Lett., 7 (12), 2445 -2448, 2005
Abstract:
If employed in THF at 0 C, LTMP metalates meta-anisic acid at the doubly activated position. In contrast, n-BuLi/t-BuOK deprotonates position C-4 preferentially at low temperature. Functionalization at C-6 requires protection of the C-2 site beforehand. As a result of these findings, a new mechanism is proposed for the heteroatom-directed ortholithiation of aromatic compounds.