%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