Intramolecular hydroamination of trisubstituted aminoallenes catalyzed by titanium complexes of diaryl substituted tridentate imine-diols

Abstract

Our laboratory has developed catalysts based on earth abundant titanium for asymmetric reactions including intramolecular hydroamination. Previously, we showed that titanium complexes of imine diol ligands showed improved enantioselectivity relative to complexes with bidentate amino alcohol ligands. As the catalyst with the highest selectivity had di-tert-butyl substitution, we sought to increase the steric protection by preparing three new ligands with diaryl substitution. These ligands were readily prepared in two steps: first, synthesis of diaryl substituted salicylaldehydes by a Suzuki coupling and second, a Schiff base condensation with a chiral amino alcohol. After characterizing the ligands, in situ hydroamination/cyclization with 6-methyl-hepta-4,5-dienylamine was carried out at temperatures ranging from 105 °C to 135 °C to give exclusively 2-(2-methyl-propenyl)-pyrrolidine with enantioselectivity up to 22 %ee. Unexpected dimerization of the catalyst resulted in reduced activity, so the reaction required a catalyst loading of 10–20%.