jo5b01767_si_002.pdf (2.03 MB)
Synthesis of Bis(oxazoline) Ligands Possessing C‑5 gem-Disubstitution and Their Application in Asymmetric Friedel–Crafts Alkylations
journal contribution
posted on 2015-10-16, 00:00 authored by Steven O’Reilly, Miriam Aylward, Caoimhe Keogh-Hansen, Brian Fitzpatrick, Helen A. McManus, Helge Müller-Bunz, Patrick J. GuiryA 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% ee) and 2-methoxyfuran (up to
95% ee) with a series of nitroalkenes. Three of the ligands (11a–c), an iron dichloride complex of
ligand 11d and two zinc dichloride complexes, were characterized
by X-ray crystallography, one with ligand 11d and the
second a bis-tert-butyl-substituted N-methylamine ligand. A direct comparison of the latter structures
clearly illustrates the gem-dimethyl effect.