This document summarizes research on using visible light-mediated photoredox catalysis to enable mild nucleophilic substitution reactions. Specifically: 1) Nucleophilic substitution reactions are important but often require harsh conditions; photoredox catalysis can activate C-O bonds under mild conditions for nucleophilic attack. 2) The method allows for the mild and scalable synthesis of unstable compounds like anhydrides and alkyl halides from carboxylic acids and alcohols. 3) The researchers, including an assistant professor and graduate students, are interested in expanding the technique to create other useful compounds and exploring its underlying photoredox mechanisms.

1. Visible Light-Mediated Photoredox
Catalysis for nucleophilic substitution
reactions in mild conditions
Marlena D. Konieczynska
Chunhui Dai
Corey R. J. Stephenson
Boston University
Sponsored by:

2. Why work on nucleophilic
substitution reactions?
• Key reaction path in organic chemistry
• Used to manufacture a lot of relevant chemicals &
precursors
– Vilsmeier-Haack reagent leads to anhydrides, halides
• Known methods often use harsh reaction
conditions
– Problematic for health & safety
– Difficult to make unstable products such as anhydrides

3. Activation of C-O bonds for nucleophilic
substitution
The C-O bond is made more reactive so that it becomes
vulnerable to attack by a nucleophile (Nu), which replaces the
group previously attached to the carbon.
light

4. Mild & scalable method
• Mild reagents and application of visible light (rather
than UV) allow use of unstable reagents and creation
of unstable reaction products
• Highly selective for the specific activated bond
• The reaction is relatively insensitive to other functional
groups near the C-O bond
• Could react a variety of C-O single bonds and
nucleophiles
• Well-suited for industrial scale-up (operational
simplicity, cheap catalyst and low usage, low amount of
waste, suitable for continuous production)

5. Example 1: Making anhydrides
from carboxylic acids
light
Anhydrides serve as precursors for amides and esters and
have applications in peptide synthesis.

6. Example 2: Making alkyl halides
from alcohols
light
Alkyl halides are important intermediates in organic
synthesis. (X = Br, I)

7. Conclusion
• We can make anhydrides and alkyl halides (building
blocks in organic synthesis and in pharmaceutical
industry) in a mild, scalable manner.  Any specific
compounds/applications you have in mind?
• We can knock off the oxygen on the carbon center and
make new bonds like it ain’t no thing.  What other
kinds of compounds would you want to do with this
technique?
• For you hardcore chemists: Check out the mechanism
itself – do you see any other routes we could use the
underlying principles?

8. About us
Corey is an Assistant Professor at Boston University.
Marlena is a third year graduate student and Chunhui is
a sixth year graduate student. Our research group is
mainly interested in applications of photoredox
catalysis and the development of new strategies and
methodologies for natural product synthesis.
Currently, the group consists of a post-doc, 9 graduate
and five undergraduate students.

9. Thanks to the challenge
sponsors
Remember: Just use your marbles!