The Radicalization of Photocatalysis

Figure 1. The Iridium catalyst used in the study. Taken from Ref. [1].

Some weeks ago I have shown you a brilliant article by Professor Corey Stephenson’s group, which involves catalysis with a photoredox catalyst. [2] Indeed, they have a number of contributions to this field recently. [1-3]


Figure 2. The atom-transfer radical addition. Taken from Ref. [1].

The radical nature of the catalytic cycle is exhibited nicely in an article on JACS this week. [1] The reaction is an atom-transfer radical addition. These types of reactions have proved to be very useful in natural product and polymer synthesis.


Figure 3. The Mechanism of the atom transfer reaction. Taken from Ref. [1].

The group has chosen a number of chemical entities who are ‘attached’ to the olefins. Other than their potential utilities, the rationale why these particular chemical functionalities are chosen can be explained by a consideration of the mechanism. In the presence of a visible light source, the Ir3+ salt enters an excited state. Upon the encounter with the halo-substituted substrate, it will lead to the generation of the single-electron organic intermediate, which is nicely stabilized by the electron-withdrawing group present in the substrate. These radical intermediate then adds to the olefin to generate the next reactive intermediate of the reaction pathway. The final addition of the departed halide leads to the ‘atom-transferred’ product.


Figure 4. The potential utilities of the reaction. Taken from Ref. [1].

The group has demonstrated the potential utilities of their approach. They succeed in the installation of a trifluoromethyl (CF3) to acyclic alkenes. As CF3 group has proved to be an important functionality in drug synthesis, a general development of this methodology will prove to be beneficial. Another use is the formation of stabilized cyclopropanes. While they are useful in their own rights, they also represent good precursors for useful chemical transformations such as [3+2] cycloadditions.

References:

1. Intermolecular Atom Transfer Radical Addition to Olefins Mediated by Oxidative Quenching of Photoredox Catalysts
John D. Nguyen, Joseph W. Tucker, Marlena D. Konieczynska, and Corey R. J. Stephenson
J. Am. Chem. Soc. 2011
dx.doi.org/10.1021/ja108560e

2.Visible-light-mediated conversion of alcohols to halides
Chunhui Dai,Jagan M. R. Narayanam& Corey R. J. Stephenson
Nature Chemistry 2011
doi:10.1038/nchem.949

Also see:

http://emockscience.blogspot.com/2011_01_01_archive.html

3. (a) Visible Light-Mediated Intermolecular C−H Functionalization of Electron-Rich Heterocycles with Malonates
Laura Furst, Bryan S. Matsuura, Jagan M. R. Narayanam, Joseph W. Tucker and Corey R. J. Stephenson
Org. Lett., 2010, 12 (13), P. 3104–3107

(b) Visible-Light Photoredox Catalysis: Aza-Henry Reactions via C−H Functionalization
Allison G. Condie, Jos C. Gonzlez-Gmez and Corey R. J. Stephenson
J. Am. Chem. Soc., 2010, 132 (5), pp 1464–1465

(c) Electron Transfer Photoredox Catalysis: Intramolecular Radical Addition to Indoles and Pyrroles
Joseph W. Tucker, Jagan M. R. Narayanam, Scott W. Krabbe and Corey R. J. Stephenson
Org. Lett., 2010, 12 (2), pp 368–371

(d) Electron-Transfer Photoredox Catalysis: Development of a Tin-Free Reductive Dehalogenation Reaction
Jagan M. R. Narayanam, Joseph W. Tucker and Corey R. J. Stephenson
J. Am. Chem. Soc., 2009, 131 (25), pp 8756–8757