Wiberg, Kenneth B. Bailey, William F. Chiral Diamines 4:  A Computational Study of the Enantioselective Deprotonation of Boc-pyrrolidine with an Alkyllithium in the Presence of a Chiral Diamine The enantioselective deprotonation of <i>N</i>-Boc-pyrrolidine (<b>1</b>) 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 <b>1</b> were located via geometry optimizations; two of these complexes would lead to abstraction of the <i>pro</i>-S hydrogen from <b>1</b>, and the other two complexes would lead to loss of the <i>pro</i>-R hydrogen. The lowest-energy intermediate complex was found to lead to loss of the <i>pro</i>-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 <i>pro</i>-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 <b>1</b> 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 <i>tert</i>-butoxycarbonyl group in <b>1</b> by a methoxycarbonyl is predicted to result in a slower deprotonation with somewhat decreased enantioselectivity. Asymmetric deprotonation of <b>1</b> using i-PrLi in combination with the <i>C</i><sub>2</sub>-symmetric diamine, (<i>S,S</i>)-1,2-bis(<i>N</i>,<i>N</i>-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. hydrogen isotope effect;3P;deprotonation;ONIUM;S hydrogen;complex 2001-07-27
    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
10.1021/ja0107733.s001