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 methoxy-(R)-1-phenylethyl)((S)- 1-phenylethyl)amide (2) and cyclohexene oxide in DEE results in the fo rmation of monomeric and dimeric complexes between 2 and cyclohexene o xide at -80 degrees C. The dimeric complex of 2 exhibited a slow cyclo hexene 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 spe ctrum of the above reaction mixture showed NOE's between lithium and c yclohexene 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 grou ps coordinate terminally to one lithium atom, Li(1), making it four-co ordinated, while the other lithium, Li(2), binds to one THF and thus i s three-coordinated. The dilithiated amide, [Li-6]lithium nylethyl)(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 consisti ng 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 ra te that was fecund to be controlled by an associative mechanism. The l ithium 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. Th e deprotonation of cyclohexene oxide using 4 gave on the other hand th e (S)-cyclohexen-1-ol with an ee of 41%. The rate of reaction was foun d 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 cyclohexen e oxide is performed by the carbanionic carbon base and not by the lit hium amide base in tt, The lithium salt )-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 am ide reagent-substrate complexes. The ee increased in the deprotonation reaction from the previous 47% to 74% in the (R)-cyclohexen-1-ol.