Photochemical Phosphorus-Enabled Scaffold Remodeling of Carboxylic Acids

09 May 2024, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


The excitation of carbonyl compounds by light to generate radical intermediates is a distinctive mode of molecular activation. These processes play important roles in organic synthesis, especially for the challenging formation of carbon-carbon bonds that conventional two-electron chemical processes are unable to achieve. This approach has historically been restricted to ketones and aldehydes, and carboxylic acids have been overlooked due to high energy requirements and their low quantum efficiency. The development of a robust and general method for the direct excitation of carboxylic acid derivatives holds significant promise for advancing the field of chemistry. A successful activation method strategy necessitates a bathochromic shift in the absorbance profile, an increase in triplet diradical lifetime, and ease of further functionalization. We present a phosphorus-based strategy through a single-flask transformation of carboxylic acids into acyl phosphonates that access synthetically useful triplet diradicals under visible light or near-ultraviolet irradiation. The use of phosphorus circumvents unproductive Norrish type I processes, promoting selectivity that enables new hydrogen atom transfer (HAT) logic and facilitates diverse reactivity. Employing this strategy promotes the efficient scaffold remodeling of carboxylic acids through various annulation, contraction, and expansion manifolds. This expansion of HAT logic enabled by easily accessed acyl phosphonates represents significant potential for pharmaceuticals, materials science, and environmental applications.


hydrogen atom transfer
triplet diradicals
scaffold remodeling
carboxylic acids

Supplementary materials

Supplemental experimental procedures
Supplemental experimental


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