With the increasing importance placed on single-enantiomer formulations by the FDA, new methods for the synthesis of complex, homochiral compounds from simple, achiral inputs are required. Pd-catalyzed asymmetric allylic alkylation (AAA), which has been used to synthesize a host of natural products, predominantly produces a linear product with unsymmetrical allylic carbonates. In contrast, the Ir-catalyzed reaction yields branched products in high yield. Presently, the Ir-catalyzed allylic substitution chemistry is limited to alcohol, amine, and stabilized enolate nucleophiles. In addition, the mechanism of how the high enantio- and diastereo-control is achieved in these reactions is unknown. A variety of new Ir-phosphoramidite complexes will be investigated for expanding the scope of this chemistry to unstabilized enolates (ketones, esters, and amides) and nitroalkanes. In all but the simplest cases, the products will contain two new, contiguous stereocenters and are difficult to synthesize in enantiopure form by currently known methods. The mechanism of the Ir-catalyzed allylic substitution will also be investigated by the synthesis, isolation, and characterization of relevant Ir-allyl complexes.
| Weix, Daniel J; Markovi?, Dean; Ueda, Mitsuhiro et al. (2009) Direct, intermolecular, enantioselective, iridium-catalyzed allylation of carbamates to form carbamate-protected, branched allylic amines. Org Lett 11:2944-7 |
| Weix, Daniel J; Hartwig, John F (2007) Regioselective and enantioselective iridium-catalyzed allylation of enamines. J Am Chem Soc 129:7720-1 |
