Chiral lithium amide solute complexes: X-ray crystallographic and NMR spectroscopic studies

We have shown by the use of multinuclear and multidimensional NMR that the reaction mixture of [Li-6]lithium (2-methoxy-(R)-1-phenylethyl)((S)-1-phenylethyl)amide (2) and cyclohexene oxide in DEE results in the formation of monomeric and dimeric complexes between 2 and cyclohexene oxide at -80 degrees C. The dimeric complex of 2 exhibited a slow cyclohexene oxide substitution rate on the NMR time scale that was found to be controlled by a dissociative mechanism. The Li-6,H-1-HOESY NMR spectrum of the above reaction mixture showed NOE's between lithium and cyclohexene oxide protons in both the monomer and dimer complexes of 2. A single-crystal X-ray diffraction experiment revealed that the solid state structure of a, crystallized from THP, is dimeric with a planar Li2N2 core constructed from amido nitrogen bridges. Both methoxy groups coordinate terminally to one lithium atom, Li(1), making it four-coordinated, while the other lithium, Li(2), binds to one THF and thus is three-coordinated. The dilithiated amide, [Li-6]lithium (2-methoxy-(R)-1-phenylethyl)(2-([Li-6]lithio)-(S)-1-phenylethyl)amide (4) was obtained by reaction of 1 equiv of [Li-6]-n-BuLi with 2 in DEE at 25 degrees C for 3-5 h. The lithium amide 4 aggregates, giving a tetrameric lithium core consisting of two molecules of 4. A titration study of 4 in DEE with THF also showed that 4 exhibited slow ligand substitution rates on the NMR time scale. The dimer 4 exhibited a slow cyclohexene oxide substitution rate that was fecund to be controlled by an associative mechanism. The lithium amide 2 has been used for the deprotonation and ring opening of cyclohexene oxide, giving an ee of 47% of the (R)-cyclohexen-1-ol. The deprotonation of cyclohexene oxide using 4 gave on the other hand the (S)-cyclohexen-1-ol with an ee of 41%. The rate of reaction was found to be initially 1.5 times faster using 4 compared to using a in DEE. This is probably due to the fact that the deprotonation of cyclohexene oxide is performed by the carbanionic carbon base and not by the lithium amide base in tt, The lithium salt of(2-methoxy-(R)-1-phenylethyl)((R)-1-phenyl-2-methylpropyl)amine (5) was prepared, as a potential reagent for the deprotonation of cyclohexene oxide, from our NMR studies of lithium amide reagent-substrate complexes. The ee increased in the deprotonation reaction from the previous 47% to 74% in the (R)-cyclohexen-1-ol.