# The Rates of Reaction Relevant to Aerobic Oxidation Catalysis by Palladium

> **NIH NIH F32** · UNIVERSITY OF PENNSYLVANIA · 2020 · $65,310

## Abstract

PROJECT SUMMARY
 Molecular oxygen is very close to the ideal oxidant: it is inexpensive, abundant, has minimal toxicity, and is
environmentally benign (i.e. “green”). Since most substrates are kinetically inert to O2, oxidations with O2 must
be catalyzed, most often by transition-metals. However, O2 is seldom used in the production of active
pharmaceutical ingredients, in part because its reactions are thought to be hard to control, leading to
overoxidation or diminished selectivity. This is a direct contradiction with the abundance of mild and selective
aerobic oxidations catalyzed by Nature; many such oxidations use a transition-metal in the active site. The goal
of this proposal is to gain a better understanding of the reactions of O2 and various transition-metal fragments.
 Palladium-catalyzed reactions are particularly promising for further development. Such catalysts have already
been used in aerobic oxidation reactions, but are relatively inefficient when compared to traditional Pd-
catalyzed transformations, such as cross-coupling. The problem lies in the reoxidation steps; if reoxidation with
O2 were more efficient, then the catalyst would be more robust! Surprisingly little is known about what factors
result in clean and fast reoxidation reactions. These factors will be elucidated by carrying out a detailed
mechanistic study: isolating and synthesizing reactive Pd0 sources, then subjecting them to (and monitoring
the reactions with) O2. The resulting PdII-peroxo species can be converted to useful, on-cycle intermediates by
a protonation reaction, and so careful mechanistic studies will be carried out on the protonation as well. A
series of these studies will provide comprehensive guidelines into ligand and substrate selection for all aerobic
palladium-catalyzed reactions, leading to an accelerated timeline for future reaction development, especially
towards the production of active pharmaceutical ingredients.

## Key facts

- **NIH application ID:** 9901588
- **Project number:** 5F32GM126639-03
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Jonathan L Kuo
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $65,310
- **Award type:** 5
- **Project period:** 2018-05-04 → 2021-08-03

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9901588

## Citation

> US National Institutes of Health, RePORTER application 9901588, The Rates of Reaction Relevant to Aerobic Oxidation Catalysis by Palladium (5F32GM126639-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9901588. Licensed CC0.

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