Solution Structures of Lithium Amino Alkoxides Used in Highly Enantioselective 1,2-Additions

Lithium ephedrates and norcarane-derived lithium amino alkoxides used to effect highly enantioselective 1,2-additions on large scales have been characterized in toluene and tetrahydrofuran. The method of continuous variations in conjunction with 6Li NMR spectroscopy reveals that the lithium amino alkoxides are tetrameric. In each case, low-temperature 6Li NMR spectra show stereoisomerically pure homoaggregates displaying resonances consistent with an S4-symmetric cubic core rather than the alternative D2d core. These assignments are supported by density functional theory computations and conform to X-ray crystal structures. Slow aggregate exchanges are discussed in the context of amino alkoxides as chiral auxiliaries.