Organic Chemistry Seminar

The development of new methods for the stereoselective synthesis of chiral amines is a compelling objective in organic synthesis as these structures are found in a large number of biologically active compounds. Yet many amine motifs remain difficult to prepare in an efficient manner, especially through complexity-building carbon–carbon bond-forming reactions and/or in atom economical ways. In this lecture, I will describe our work in two areas of enantioselective catalysis to prepare chiral amines: 1) carbon–carbon bond formations via electrophilic additions to 2-azadienes, which act as enamine umpolung reagents, and 2) nucleophilic additions of aliphatic amines and anilines to acyclic 1,3-dienes (hydroamination).

Cu-catalyzed reductive couplings of azadienes—virtually unexplored reagents—with ketones and imines has enabled the synthesis of challenging, sterically congested vicinal amino alcohols and diamines, while Pd-catalyzed fluoroarylation of difluoroazadienes has permitted access to alpha-trifluoromethyl benzylic amines. In the latter area, the development of a family of electron deficient Pd–PHOX catalysts for hydrofunctionalization has enabled regio- and enantioselective addition of Lewis basic amines to dienes that furnish allylic amines. Extension to diene hydroalkylation with beta-dicarbonyl-like pronucleophiles delivers myriad unsaturated carbonyl products in atom economical carbon–carbon bond-forming transformations.