Synthesis of Bis(oxazoline) Ligands Possessing C‑5 <i>gem</i>-Disubstitution and Their Application in Asymmetric Friedel–Crafts Alkylations

A series of eight novel bis­(oxazoline) ligands incorporating <i>gem</i>-disubstitution on one of the oxazoline rings were prepared from (<i>S</i>)-valine. These ligands are designed as a cost-effective alternative to similar ligands possessing an oxazolinyl C(5)-<i>tert</i>-butyl group derived from expensive (<i>S</i>)-<i>tert</i>-leucine. Four of the ligands possess a C(4)-<i>gem</i>-dimethyl group and four a C(4)-<i>gem</i>-diphenyl group adjacent to the C(5)-isopropyl substituent. Zinc complexes of ligands <b>11a</b>–<b>h</b>, along with non-C(4)-<i>gem</i>-disubstituted analogues <b>1a</b>–<b>g</b>, were effective in the Friedel–Crafts alkylation of both indole (up to 74% ee) and 2-methoxyfuran (up to 95% ee) with a series of nitroalkenes. Three of the ligands (<b>11a</b>–<b>c</b>), an iron dichloride complex of ligand <b>11d</b> and two zinc dichloride complexes, were characterized by X-ray crystallography, one with ligand <b>11d</b> and the second a bis-<i>tert</i>-butyl-substituted <i>N</i>-methylamine ligand. A direct comparison of the latter structures clearly illustrates the <i>gem</i>-dimethyl effect