%0 Journal Article %A Wiberg, Kenneth B. %A Bailey, William F. %D 2001 %T Chiral Diamines 4:  A Computational Study of the Enantioselective Deprotonation of Boc-pyrrolidine with an Alkyllithium in the Presence of a Chiral Diamine %U https://acs.figshare.com/articles/journal_contribution/Chiral_Diamines_4_A_Computational_Study_of_the_Enantioselective_Deprotonation_of_Boc-pyrrolidine_with_an_Alkyllithium_in_the_Presence_of_a_Chiral_Diamine/3634449 %R 10.1021/ja0107733.s001 %2 https://acs.figshare.com/ndownloader/files/5723199 %K hydrogen isotope effect %K 3P %K deprotonation %K ONIUM %K S hydrogen %K complex %X The enantioselective deprotonation of N-Boc-pyrrolidine (1) with i-PrLi−(−)-sparteine has been studied at theoretical levels up through B3P86/6-31G*. Four low-energy intermediate complexes involving i-PrLi−(−)-sparteine and 1 were located via geometry optimizations; two of these complexes would lead to abstraction of the pro-S hydrogen from 1, and the other two complexes would lead to loss of the pro-R hydrogen. The lowest-energy intermediate complex was found to lead to loss of the pro-S hydrogen as observed experimentally. Transition states for the deprotonations were located using the synchronous transit-guided quasi-Newton method. The calculated activation enthalpy for transfer of the pro-S hydrogen within the lowest-energy intermediate complex, 10.8 kcal/mol, is reasonable for a reaction that occurs at a relatively low temperature, and the calculated kinetic hydrogen isotope effect is in agreement with experimental data. The lower enantioselectivity observed experimentally for deprotonation of 1 using t-BuLi−(−)-sparteine is attributed to a transition-state effect due to increased steric interaction engendered by the bulky t-BuLi. Replacement of the tert-butoxycarbonyl group in 1 by a methoxycarbonyl is predicted to result in a slower deprotonation with somewhat decreased enantioselectivity. Asymmetric deprotonation of 1 using i-PrLi in combination with the C2-symmetric diamine, (S,S)-1,2-bis(N,N-dimethylamino)cyclohexane, was calculated to be much less selective than is the deprotonation mediated by (−)-sparteine as observed experimentally. The relative energies of the intermediate complexes were fairly well-reproduced by ONIUM calculations in which the sparteine ligand less its nitrogen atoms was treated by molecular mechanics and the remainder of the complex was treated by quantum mechanics. %I ACS Publications