Atom Economic Asymmetric Aldol and Related Reactions

Carbonyl addition reactions are very prominent in the synthesis of complex molecules. The classic aldol is illustrative, but the reaction suffers from poor chemo- and regioselectivity. Researchers in the laboratory of Dr. Barry Trost at Stanford University have developed a catalytic system that provides an exceptionally efficient way to effect aldol and the related nitroaldol to form chiral, enantiopure adducts. Furthermore, other nucleophiles like cyanide and terminal alkynes are suitable. In addition to aldehydes, imines also serve as acceptors to provide chiral enantiopure amines.

The catalyst involves a novel dinuclear main group metal (presently mainly zinc) complex that self assembles with a chiral ligand to produce compounds that are important building blocks for further organic synthesis. Because of the extraordinary chemoselectivity, diastereoselectivity, and enantioselectivity of the catalysis, this technology should be particularly useful for the synthesis of pharmaceuticals, natural products, and agrichemicals.

Ongoing Research:

The potential of this catalyst system has been scarcely examined. On-going programs are examining the breadth of possible donors and acceptors suitable for catalysis with these complexes. For example, promising leads for asymmetric conjugate additions and formation of cyclic amines are being developed.