Description:

"New Strategies for the Catalytic Enantioselective Synthesis of Chiral Amines and Other Challenging Scaffolds"

Steven Malcolmson, PhD
Assistant Professor of Chemistry
Duke University

Abstract
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 and enynes (hydroamination).

In the former area, 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 fluoro-arylation of difluoroazadienes has permitted access to alpha-trifluoromethyl benzylic amines. In the latter, the development of a family of electron deficient Pd–PHOX catalysts for hydrofunctionalization has enabled regio- and enantioselective addition of highly Lewis basic amines to dienes, furnishing allylic amines with a variety of allylic and olefin substituents. Hydroaminations of enynes has led to the isolation of chiral di- and trisubstituted allenes. Extension to diene hydroalkylation with beta-dicarbonyl-like pronucleophiles delivers myriad unsaturated carbonyl products in atom economical carbon–carbon bond-forming transformations.

Hosted by Professor Karl Scheidt
This is a Chemical Biology and Drug Discovery Research Cluster event.

Refreshments will be served.