Enantioselective Radical Additions
Synthesis and Evaluation of DBFOX Ligand

Enantioselective C-C bond formation is an important goal in organic synthesis. Some years ago, free radical chemists felt that it is time to introduce a powerful free-radical variant of the analogous carbanionic reactions. Despite the general success of applying knowledge gained in stereoselective carbanionic chemistry to radical reactions, intermolecular radical reaction have their own particularities, as chemists have started to learn.
DBFOX/Ph, a tridentate bisoxazoline ligand introduced by Kanemasa’s group in 1997, was studied in conjugate radical addition reactions with cinnamoyloxazolidinones. In a nutshell, the results show that substrate activation by the Lewis acid is essential for high asymmetric induction and yields.
Synthesis of DBFOX

The ligand synthesis proved to be especially challenging, even though you might think that this shouldn’t be the case given the ample precedent of bisoxazoline synthesis. Our route represents the most efficient and convenient route available to-date, and these findings will soon appear in Organic Syntheses.
Publications
Full paper: U. Iserloh, D. P. Curran and S. Kanemasa, Enantioselective Conjugate Radical Addition Reactions Mediated by Chiral Lewis Acid Complexes of (R,R)-4,6-Dibenzofurandiyl)-2,2′-bis(4-phenyloxazoline) (DBFOX/Ph). Tetrahedron: Asymmetry, 1999, 10, 2417-28. Download PDF.
Full paper: U. Iserloh, Y. Oderaotoshi, S. Kanemasa, D. P. Curran, Synthesis of (R,R)-4,6-dibenzofurandiyl-2,2′-bis (4-phenyloxazoline) (DBFOX/PH) - A novel tridentate ligand. Organic Syntheses, 2003, 80 46-56.
Additional Reading
- Review: Enantioselective Radical Reactions (Iserloh)
- Use of Lewis Acids in Free Radical Rxns (Renault and Gerster)
- Review: Enantioselective Radical Reactions (Sibi)