Organic Chemistry Seminar
Steven Malcolmson was born and raised in Boston, MA and received a B.A. in Chemistry from Boston University in 2004. He attended Boston College for graduate school, developing new Mo-based catalysts for stereoselective olefin metathesis under the mentorship of Prof. Amir Hoveyda, in collaboration with Prof. Richard Schrock (MIT). After obtaining a Ph.D. in 2010, Steve studied natural product biosynthesis as an NIH postdoctoral fellow with Prof. Chris Walsh at Harvard Medical School. He began his independent career at Duke University in 2013 where he is currently an Assistant Professor of Chemistry.
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.