Chiral Organolithium Complexes: The Effect of Ligand Structure on the Enantioselective Deprotonation of Boc-Pyrrolidine

Article abstract of DOI:10.1021/jo00130a014

The efficacies of a number of s-BuLi/chiral ligand complexes as reagents for the asymmetric deprotonation of Boc-pyrrolidine (1) to provide enantioenriched 2-lithio-Boc-pyrrolidine (2) have been evaluated by the conversion of 2 to 2-(trimethylsilyl)-Boc-pyrrolidine (3).The syntheses of new enantioenriched proline-based and bispidine ligands are described.The most effective newly examined ligands are the diproline-based diamino alcohol 20 and the α-methylbenzylamine-derived bispidine 35, which provided (S)-3 and (R)-3 with enantiomeric excesses of 72percent and 75percent, respectively.Use of the ligand (-)-isosparteine (28) resulted in lower conversions and enantioselectivities than (-)-sparteine (27).A rationale is proposed to explain the relative rates of the lithiation of 1 by s-BuLi/TMEDA, 27, or 28 complexes and the remarkable effectiveness of (-)-sparteine as the best chiral ligand examined to date.