Regioselective, diastereoselective, and enantioselective lithiation-substitution sequences: Reaction pathways and synthetic applications

The conversion of 1 to 2 to 3 provides a convenient and efficient synthetic strategy for regioselective, diastereoselective, and enantioselective syntheses. The processes by which selectivity is introduced in these lithiation-substitution sequences are shown in Scheme 1. After initial complexation, a regioselective or diastereoselective deprotonation can occur. In an asymmetric deprotonation, the enantioenriched 2 or 2·L * retains its configuration and reacts stereoselectively with electrophiles. If 2 is produced in racemic form, two different diastereoselective pathways for asymmetric substitution are available. The pathway which involves selective formation of one nonequilibrating complex is a dynamic thermodynamic resolution. If the diastereomeric complexes are in rapid equilibrium, a pathway of dynamic kinetic resolution is followed. While the cases we have discussed involve (-)-sparteine as the chiral ligand, the scheme applies to other ligands as well as to reactions involving chiral auxiliaries.