Synthesis of an Advanced Precursor of 6 Rivastigmine: Cinchona-derived Quaternary Ammonium Salts as Organocatalysts for Stereoselective Imine Reductions

The enantioselective redn. of ketoimines has been successfully realized, using trichlorosilane as the stoichiometric reducing agent in the presence of catalytic amts. of a Lewis base, specifically a Cinchona deriv. For the first time, a novel class of derivs. was studied, featuring a picolinamide unit bound to the alkaloid scaffold, further functionalized as quaternary ammonium salt at the quinuclidine ring. Excellent yields and from good to high enantioselectivities (up to 92% ee) were obtained in the redn. of ketoimines. The novel catalysts were successfully employed in the synthesis of an enantiomerically pure advanced precursor of the blockbuster drug rivastigmine.