Addition of carbon nucleophiles to imines is one of the most widely utilized C-C bond forming reactions in organic chemistry and thus development of asymmetric versions of this reaction is an important endeavor. Recently, progress toward this goal has been achieved with N-aryl imines. Unfortunately, the existing catalytic systems do not provide high ee's with N-aryl imines, except those derived from 2-hydroxyaniline. A new catalyst system needs to be developed that can catalyze the asymmetric addition of nucleophiles to a wide array of N-aryl imines. This important class of substrates can act as precursors to an array of natural products and drug targets containing aniline-bearing stereogenic centers. This proposal outlines the design of two new chiral Lewis acid frameworks developed to catalyze the enantioselective addition to N-aryl imines. The proposed catalysts arise from modification of Jacobsen's chiral (salen)AI(lll) Strecker catalyst. The first proposed catalyst incorporates planar chiral ferrocenyl ligands into a Schiff base framework. The second proposed catalyst structure is derived from alpha-pinene and combines two molecules of pinene into a unique C2-symmetric ligand scaffold. Targeted transformations are the Strecker and Mannich reactions as well as the aza-Diels-Alder reaction to form enantioenriched tetrahydroquinolines.
| Peterson, Emily A; Jacobsen, Eric N (2009) Enantioselective, thiourea-catalyzed intermolecular addition of indoles to cyclic N-acyl iminium ions. Angew Chem Int Ed Engl 48:6328-31 |
