The enantioselective lithiation of N-Boc-pyrrolidine using sec-butyllithium and isopropyllithium in the presence of sparteine-like diamines has been studied experimentally and computationally at various theoretical levels through to B3P86/6-31G*. Of the (-)-cytisine-derived diamines (N-Me, N-Et, N-Bu-n, N-CH2t-Bu, N-Pr-i) studied experimentally, the highest enantioselectivity (er 95:5) was observed with the least sterically hindered N-Me-substituted diamine, leading to preferential removal of the pro-R proton i.e., opposite enantioselectivity to (-)-sparteine. The experimental result with the N-Me-substituted diamine correlated well with the computational results: at the B3P86/6-31G* level, the sense of induction was correctly predicted; the lowest energy complex of isopropyllithium/diamine/N-Boc-pyrrolidine also had the lowest activation energy (DeltaH(double dagger) = 11.1 kcal/mol, DeltaG(double dagger) = 11.5 kcal/mol) for proton transfer. The computational results with the N-Pr-i-substituted diamine identified a transition state for proton transfer with activation energies of DeltaH(double dagger) = 11.7 kcal/mol and DeltaG(double dagger) = 11.8 kcal/mol (at the B3P86/6-31G* level). Although comparable to (-)-sparteine and the N-Me-substituted diamine, these DeltaH(double dagger) and DeltaG(double dagger) values are at odds with the experimental observation that use of the N-Pr-i-substituted diamine gave no product. It is suggested that steric crowding inhibits formation of the prelithiation complex rather than increasing the activation enthalpy for proton transfer in the transition state. Three other ligands (N-H and O-substituted as well as a five-membered ring analogue) were studied solely using computational methods, and the results predict that the observed enantioselectivity would be modest at best.