Lithiation of a Silyl Ether: Formation of an ortho-Fries Hydroxyketone

摘要

A hydroxy-directed alkylation of an N,N-diethylar-ylamide using CIPE-assisted α-silyl carbanions (CIPE = complex-induced proximity effect) has been developed using a simple reagent combination of LDA (lithium diisopropyl-amide) and chlorosilane. A study of the mechanism, and the application of the procedure to an anionic Snieckus-Fries rearrangement for a highly efficient synthesis of the potent phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002, are reported.