ChemRxiv
These are preliminary reports that have not been peer-reviewed. They should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information. For more information, please see our FAQs.
CuLMCTManuscript_unformat_April19_final.pdf (811.86 kB)

Ligand-to-Copper Charge Transfer: A General Catalytic Approach to Aromatic Decarboxylative Functionalization

preprint
submitted on 20.04.2021, 04:02 and posted on 20.04.2021, 13:05 by Tiffany Q. Chen, P. Scott Pedersen, Nathan W. Dow, Remi Fayad, Cory E. Hauke, Michael C. Rosko, Evgeny O. Danilov, David C. Blakemore, Anne-Marie Dechert-Schmitt, Thomas Knauber, Felix N. Castellano, David W. C. MacMillan

Aryl carboxylic acids are valuable, stable, and abundant functional handles in organic synthesis. Historically, their activation with established two-electron methods requires forcing conditions, and such protocols are limited in scope. In contrast, we envisioned that copper’s ability to generate open-shell species through ligand-to-metal charge transfer (LMCT), combined with its unique capacity to act as a potential aroyloxy and aryl radical reservoir, could mediate facile light- and copper-enabled aromatic decarboxylative functionalization by mitigating undesired reactivity of radical intermediates formed during aromatic decarboxylation. We report herein a general copper-LMCT open-shell activation platform for aromatic halodecarboxylation. Catalytic decarboxylative chlorination, bromination, and iodination of diverse (hetero)aryl carboxylic acids have been achieved to provide broadly used electrophilic cross-coupling handles from widely available aromatic acid precursors. Notably, decarboxylative fluorination of aryl carboxylic acids ­– a long-standing challenge in the field of organic synthesis – is readily accessible over a wide breadth of (hetero)aryl substrates. Ultrafast transient absorption (TA) spectroscopy experiments in combination with steady-state UV-vis spectroscopy studies are consistent with the proposed copper-LMCT mechanism, supporting the mechanistic basis of this activation platform.

Funding

Photoredox Catalysis Applications in Organometallics and Chemical Biology

National Institute of General Medical Sciences

Find out more...

Bioinspired Light-Escalated Chemistry (BioLEC)

Basic Energy Sciences

Find out more...

History

Email Address of Submitting Author

tqc@princeton.edu

Institution

Princeton University

Country

USA

ORCID For Submitting Author

0000-0001-9096-8856

Declaration of Conflict of Interest

No conflict of interest

Exports