# Dearomative Functionalization with Arenophiles

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2021 · $295,111

## Abstract

PROJECT SUMMARY
 Aromatic hydrocarbons (arenes) are some of the most elementary feedstock chemicals, produced
annually on a million metric ton scale. Chemical transformations of these compounds play a fundamental role in
everyday life; for example, in the production of polymers, paints, agrochemicals, and pharmaceuticals.
Dearomatization reactions convert simple, readily available arenes into more synthetically useful unsaturated
intermediates. Our long term goal is to provide new chemical transformations and strategies that will selectively
introduce functionality and, consequently, greatly expand the dearomative chemical toolbox.
 Small, heteroatom-containing complex molecules are common motifs of biological (as well as
pharmaceutical and agrochemical) relevance and are highly desired in medicinal chemistry, but they are also
often difficult to access. Selective transformations of aromatic compounds could provide a more direct route to
such desirable targets; however, the many challenges associated with dearomative functionalization have left
these types of reactions widely underdeveloped. The proposed research strives to address this need by bridging
the gap between dearomatization and alkene chemistry. Fundamentally, the goal of this proposal is to access
desirable structural motifs from simple aromatic compounds by developing dearomative functionalizations using
small molecules – arenophiles – that enable reactions of isolated alkenes in an arene substrate. Our preliminary
results demonstrate that well-established olefin reactions, such as dihydroxylation and reduction can now be
more directly applied to arenes. Additionally, arenophiles, in combination with transition metal catalysis, provide
uniquely reactive substrates for nucleophilic substitution reactions, and could enable the rapid synthesis of a
diverse range of aminofunctionalized alicyclic compounds. While many known attempts to directly functionalize
aromatic compounds result in overreaction or decomposition, this arenophile-based strategy permits selective
and controlled introduction of functional complexity. Finally, this approach provides products that are both
challenging to synthesize via existing methods and complementary to those acquired through biological or
chemical dearomative processes.
 Overall, the development of a general dearomative functionalization platform with arenophiles has the
potential to make a profound impact on the pharmaceutical, agricultural, and materials sciences by providing
expedient access to complex small molecules with tailored properties from simple and readily available arenes.

## Key facts

- **NIH application ID:** 10200084
- **Project number:** 5R01GM122891-05
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** David Sarlah
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $295,111
- **Award type:** 5
- **Project period:** 2017-07-15 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10200084

## Citation

> US National Institutes of Health, RePORTER application 10200084, Dearomative Functionalization with Arenophiles (5R01GM122891-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10200084. Licensed CC0.

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