ENANTIOSELECTIVE LITHIATION-SUBSTITUTION OF NITROGEN-CONTAINING HETEROCYCLES

摘要

The conversion of A'-Boc heterocycles into their enantioenriched cc-substituted derivatives by an enantioselective lithiation-substitution process mediated by a strong organolithium base and a chiral ligand was first demonstrated by Kerrick and Beak. An example from this seminal contribution is shown in Scheme 1. Lithiation of A'-Boc pyrrolidine (1) is carried out using s-BuLi and the chiral diamine ligand (-)-sparteine (LI) in Et20 at -78°. Subsequent trapping of the lithiated intermediate with Me3SiCl produces a-substituted A'-Boc pyrrolidine (S)-2 with high enantioselectivity. A gram-scale version was subsequently reported (87% yield).