Synthesis of Bis(oxazoline) Ligands Possessing C-5 gem-Disubstitution and Their Application in Asymmetric Friedel-Crafts Alkylations

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