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Configurationally Labile Lithiated O ‐Benzyl Carbamates: Application in Asymmetric Synthesis and Quantum Chemical Investigations on the Equilibrium of Diastereomers
Author(s) -
Lange Heiko,
Huenerbein Robert,
Fröhlich Roland,
Grimme Stefan,
Hoppe Dieter
Publication year - 2008
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.200700261
Subject(s) - chemistry , deprotonation , diastereomer , sparteine , computational chemistry , quantum chemical , oxazoline , butyllithium , medicinal chemistry , organic chemistry , molecule , catalysis , ion
The title compounds were generated by deprotonation of different benzyl‐type carbamates with sec ‐butyllithium in the presence of chiral diamines (−)‐sparteine or diisopropyl and di‐ tert ‐butyl bis(oxazoline)s. These lithiated species exhibit configurational lability at −78 °C. In the case of the chiral di‐ tert ‐butyl bis(oxazoline), the equilibrium of the epimeric complexes can be used synthetically to obtain highly enantioenriched secondary benzyl carbamates. The enantiodetermining step was proven to be a dynamic thermodynamic resolution. The absolute configurations of the products were determined, and the stereochemical pathways of selected substitution reactions were thus elucidated. High‐level quantum chemical investigations were performed to gain insight into the experimentally investigated system. To obtain an accuracy for the energy difference (ΔΔ H ) between two epimeric complexes of about 0.5 kcal mol −1 as well as the correct sign, a theoretical procedure was established. It included geometry optimization at the dispersion‐corrected DFT level, computation of zero‐point vibrational energies, and single‐point SCS‐MP2 energy calculations with large atomic‐orbital basis sets.