# MIRA: C(sp3)-H Heteroatom Incorporation Using Photoexcited Nitroarenes

> **NIH NIH R35** · NEW YORK UNIVERSITY · 2024 · $384,480

## Abstract

Project Summary
Heteroatom units, such as C(sp3)–OH and C(sp3)–NH2, are prevalent motifs in many pharmaceutically
relevant drugs and natural products. Methods to incorporate these important functional groups at the expense
of C–H bonds rely on the use of non-commercial heteroatom transfer agents, precious transition metals,
and/or costly engineered enzymes. Also, these methods often require harsh exogenous oxidants to promote the
C–heteroatom bonding event, which greatly limits substrate scope. In this proposal, we highlight the
employment of economical nitroarenes as versatile reagents that can serve as the C(sp3)–H bond activator and
the oxygen atom source for the C–H hydroxylation of aliphatic systems under benign visible-light irradiation.
Notably, the heteroatom transfer event occurs anaerobically, thereby allowing for significant expansion of
substrate scope compared to previous state-of-the-art methods. Asymmetric C–H hydroxylation protocols can
be achieved with the use of recyclable photoexcited nitroarene atropisomers, leading to a sustainable approach
for the late-stage installation of chiral alcohol groups. The development of a universal platform for C–H
heteroatom incorporation of aliphatic systems can be engendered under this reaction paradigm via a formal
polar crossover event and coupling with nucleophiles. The merger of chiral H-bond donor catalysts or chiral
phosphoric acid catalysts to this approach can enable a general platform for asymmetric heteroatom
incorporation directly from C–H bonds without the need for a leaving group, which is an underdeveloped area
in synthesis. For C–N bond formation, chemoselective transfer of the nitrogen atom from the nitroarene
moiety to aliphatic systems can be achieved under photoirradiation empowering facile formation of imines
directly from methylene units. In-situ hydrogenation of the formed imine products generates amines formally
from C–H bonds; thus, resulting in a C–H amination event from the multi-fold reactivity of photoexcited
nitroarenes. The synthetic utility of the proposed protocols illustrates that late-stage C–H heteroatom
incorporation events promoted by photoexcited nitroarenes can provide a cost-effective means for the
synthesis of complex molecular scaffolds. Overall, novel C–H heteroatom events can be achieved in a mild,
general, and sustainable manner by exploiting the multifunctional role of photoinduced nitroarenes. It is
anticipated that photoexcited nitroarenes will serve as useful tools for the anaerobic heteroatom incorporation
of organic molecules.

## Key facts

- **NIH application ID:** 10894091
- **Project number:** 5R35GM150777-02
- **Recipient organization:** NEW YORK UNIVERSITY
- **Principal Investigator:** Marvin Parasram
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $384,480
- **Award type:** 5
- **Project period:** 2023-08-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10894091

## Citation

> US National Institutes of Health, RePORTER application 10894091, MIRA: C(sp3)-H Heteroatom Incorporation Using Photoexcited Nitroarenes (5R35GM150777-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10894091. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*