TGA-FTIR Guided Ligand Evaluation for Iron Photocatalyzed Decarboxylative Giese Reactions

04 September 2023, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


A general Fe photocatalyzed Giese reaction was developed using a unique analytical technique for synthetic organic chemistry: Thermal Gravimetric Analysis-Fourier Transform Infrared Spectroscopy (TGA-FTIR). The optimized Giese conditions proceed with low loadings of a simple Fe salt with a commercial amine ligand and obviates the need for the traditional large excess of one coupling partner to facilitate radical capture. This protocol enables the successful coupling of primary, secondary, and tertiary carboxylic acids with sterically hindered, cyclic, and acyclic electron-deficient acceptors. Additionally, methylation of acceptors proceeds smoothly at room temperature from commercial acetic acid. Protected amines, heterocycles, and electron-rich alkenes are well-tolerated, enabling functionalization of Osimertinib, a kinase inhibitor for non-small-cell lung carcinoma. Preliminary investigation of the reaction mechanism was consistent with formation of an Fe-carboxylate species followed by a light-promoted decarboxylation. TGA-FTIR was used to evaluate ligand trends for Fe carboxylates. Using 30-minute decomposition times a correlation was revealed between Fe carboxylate CO2 extrusion time and the yield attained with aliphatic amine ligands coordinated to Fe. Less substituted amine ligands gave greater yields of product and could eliminate the need for stoichiometric quantities of base and provide control for decarboxylation chemistry over hydrogen atom transfer chemistry.


Fe Photocatalysis
Decarboxylative Giese

Supplementary materials

Supplementary Materials
This document contains extended optimization data, general procedures, TGA-FTIR analytical techniques, and spectroscopic characterization.


Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.