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 <i>S</i>₄-symmetric cubic core rather than the alternative <i>D</i>_2<i>d</i> 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