We have developed the first catalytic enantioselective allyaltion utilizing allyl indium reagents and have applied them to the synthesis of chiral amines. Catalytic BINOL additives generate a chiral In-BINOL Lewis acid complex in situ. When applied to ketimines this reaction affords extremely high enantioselectivity for both aromatic and aliphatic substrates!
Allyl indium reagents can be prepared from allylic acetates via a Pd(0)-catalyzed reaction. This process is catalytic in Pd.
We have utilized this ümpolung reaction in two ways. We have demonstrated the proof of principle for utilizing a chiral Pd catalyst to generate in situ a chiral allyl indium reagent. We have also applied the reaction to the allylation of hydrazones with our chiral BINOLs.
Bismuth is a cheap, safe and environmentally benign metal. We have long been interested in Bi(III) Lewis acid catalysis for a variety of reactions including Friedel-Crafts reactions and halide activation. We have also developed a novel Bi(0)-mediated, chiral Bi(III)-catalyzed allylation of ketones that provide high enantioselectivity in protic solvents. For example, the allylation of isatin derivatives with allyl iodide and bismuth metal catalyzed by a Bi-pybox Lewis acid proceeds with up to 88% enantioselectivity.
We are currently striving to understand the nature of the catalyst and its mechanism of asymmetric induction. Preliminary studies show a marked nonlinear effect with respect to the ligand ee. This would imply that more than one chiral ligand is involved in the enantiodifferentiating step. By mass spectrometry we have observed two chiral Bi species. One possesses a single chiral ligand and another bears two chiral ligands. Xray crystallography revealed a unique chiral bismuth complex which sandwiches a sodium cation between two arenes of the pybox ligand. We do not believe this is the catalyst involved in the allylation reaction. However, it opens the door to more new and exciting research.