# Innovative Transformations of Fundamental Synthetic Building Blocks

> **NIH NIH R35** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $497,514

## Abstract

Project Summary: The value of chemical synthesis in health-related research is closely tied to the ability to
efficiently generate medicinal agents from readily available materials. This MIRA application seeks to continue
our efforts centered on the development of innovative synthetic transformations of fundamental building blocks.
The long-term goal of this program is to identify promising new modes of chemical reactivity that facilitate the
rapid discovery and development of small molecules for biomedical applications. The overall objective of this
application is to develop a diverse set of enabling transformations featuring widely available synthetic
feedstocks. Site-selective transformations of aliphatic C–H bonds hold enormous promise in streamlining drug
synthesis and expediting access to novel analogs of biologically relevant compounds via late-stage
functionalization. Despite this potential, synthetic capabilities remain limited to a narrow subset of possible C–H
transformations. Moreover, site- and chemoselective derivatization of the functional group rich substrates most
relevant to drug development remains a challenge. We seek to develop intermolecular aliphatic C–H
functionalizations that open access to new chemical space with drug-like substrates and proceed with high
levels of reagent-dictated site selectivity. This research is based on the hypothesis that radical-chain,
intermolecular C–H functionalizations using tuned heteroatom-centered radicals can proceed with exceptional
levels of efficiency and selectivity on complex, medicinally relevant substrates, enabling otherwise inaccessible
C–H transformations. Our approach will leverage the reactivity of tuned heteroatom-centered radicals with a
range of unique coupling partners to achieve new site- and chemoselective transformations.
 Another major goal is to develop new catalytic platforms of earth-abundant metals that enable valuable
transformations of diverse synthetic feedstocks. Hydrocarbonylations of alkenes have demonstrated utility in
the synthesis of medicinally relevant compounds, yet many attractive transformations remain inaccessible
owing to limitations in catalysis. The development of catalytic C–C bond constructions that use easily-accessed
alkyl electrophiles is another major challenge. We seek to establish new reactivity manifolds in earth-abundant
metal catalysis which we hypothesize will enable solutions to these challenges. Our objectives include the
development of both new hydrocarbonylations of alkenes that feature a range of common nucleophiles and
catalytic C–C bond-forming couplings of unactivated alkyl chlorides. The rationale of the proposed research is
that the practical and selective reactions produced will facilitate access to diverse synthetically and medicinally
valuable small molecules. Our proposed research is innovative because it develops several new modes of
chemical reactivity to generate new, powerful bond-forming reactions. These contributions...

## Key facts

- **NIH application ID:** 10840530
- **Project number:** 2R35GM131708-06
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Erik John Alexanian
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $497,514
- **Award type:** 2
- **Project period:** 2019-05-01 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10840530

## Citation

> US National Institutes of Health, RePORTER application 10840530, Innovative Transformations of Fundamental Synthetic Building Blocks (2R35GM131708-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10840530. Licensed CC0.

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