Title: Synthesis Through C–C Bond Scission

Professor Ohyun Kwon

Department of Chemistry and Biochemistry

University of California, Los Angeles

Hosted by: Dr. Junqi Li 

Abstract: The topic of this talk is the radical chemistry based on C–C bond scission. The presentation will begin with another area of research endeavors in my group—phosphorus organocatalysis. It then will present how our need to create chiral phosphines, CarvoPhos, of particular configuration inspired our invention of a series of new reactions based on C–C bond cleavage. To be specific, we have implemented one-pot processes to ozonize alkenes into α-methoxyhydroperoxides, for subsequent Fe(II)-mediated reductive fragmentations that yield alkyl radical intermediates. Various radical trapping agents are capable of seizing the alkyl radical, enabling the conversion of the alkene C(sp3)–C(sp2) bond to C(sp3)–H, C(sp3)–S, C(sp3)–O, C=O, C(sp3)–C(sp2), C(sp3)–C(sp), C(sp3)–halogen bonds, the last two of which were facilitated by catalytic Fe(II) with vitamin C as the stoichiometric reductant. More recently implemented is a pathway for the Cu(I)-catalyzed dealkenylative amination for the late-stage modification of hormones, pharmaceutical reagents, peptides, and nucleosides. Beyond alkenes, generalized methods for converting the C(sp3)–C(sp2) bonds of ketones to C(sp3)–X linkages (X = H/C/heteroatom) will also be presented.

Utilities of our inventions, particularly of “hydrodealkneylation” and “aminodealkenylation” are illustrated by facile production of medicinally relevant molecules shown below:

Bio: Ohyun Kwon received her B.S. (1991) and M.S. (1993) from Seoul National University in South Korea. In 1993, she came to the U.S. to pursue her Ph.D. (1998) from Columbia University under the guidance of S. J. Danishefsky. Her thesis work involved the synthesis of biologically significant glycolipid, asialo GM1 and Globo-H human breast tumor antigen molecule, as well as complex phomoidride terpenoids, CP-225,917 and CP-263,114. She then went to Harvard University as a Howard Hughes Postdoctoral Fellow to study chemical genetics in S. L. Schreiber’s lab. There, she completed a diversity-oriented combinatorial synthesis (DOS) of a library of muticyclic compounds, as well as a library of macrocycles. Kwon joined the faculty as an assistant professor at UCLA in 2001. She has been a member of the Molecular Biology Institute (MBI) and UCLA Jonsson Comprehensive Cancer Center (JCCC) since 2005.