Selectivity in the aggregates of the chiral organolithium N-Boc-2-lithiopiperidine with a chiral ligand: a DFT study

In this paper the aggregates of the chiral organolithium N-Boc-2-lithiopiperidine Boc=CO₂C(CH₃)₃], which play an important role in the formation of chiral 2-substituted piperidines found in many alkaloid structures and medicinal compounds, have been investigated within the framework of Density Functional Theory (DFT) calculations. In the complex structures, the lithium atoms are tetra-coordinated, the diaminoalkoxide ligand is tridentate to one lithium atom and forms a chelate with the substrate which is stabilized by the solvent diethyl ether. The same type of bonding was observed for all the different ligand-bound structures; for ligands 6 and 7, which have bulky substituents, selectivity was in agreement with experiment. The results shed light on the microscopic structures of these species and suggest a potential ligand, 11, to yield high enantioselectivity.