Modification of the Duff Formylation Reaction
Dante D. Podesto, Rina Salurialam
Mentor: Scott Rychnovsky
The Duff reaction is an electrophilic aromatic substitution reaction that regioselectively
installs a formyl group at the orth or para position of a phenolic ring. The reaction is used
in the synthesis of precursors for catalyst ligands and natural products. It has a significant
advantage to similar reactions due to its inexpensive and non-toxic reagents.
Traditionally, the Duff formylation is a low to moderately yielding reaction. The issues
with product yields were first addressed successfully by Dr. Kevin Banhck and Professor
Rychnovsky during the total synthesis of Kendomycin. During the optimization of the
reaction they discovered the use of water as a reagent increased productivity. Our
research has examined the potential use of a stoichiometric amount of water on a wide
range of phenolic substrates. We have demonstrated that the addition of stoichiometric
water provides a 10–20% increase in product yields of these substrates. We have also
optimized the timing of the reaction by use of a microwave reactor. Our studies have
demonstrated that microwave assisted synthesis can substantially decrease the reaction
time, while providing comparable yields obtained using conventional heating methods.
We are confident that our findings will benefit the synthetic organic community by
providing several template procedures that specifically address the different conditions
required for substrates of differing reactivity.