# Innovative Transformations of Fundamental Synthetic Building Blocks

> **NIH NIH R35** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $495,983

## 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 merge
two productive NIGMS-funded projects 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 to 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
using either unactivated aliphatic C–H bonds or alkyl electrophiles. 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, few intermolecular C–H
functionalizations of preparative value exist. We seek to develop practical, intermolecular aliphatic C–H
functionalizations that introduce diverse chemical functionality and proceed with high levels of site selectivity.
This research is based on the hypothesis that radical-mediated intermolecular C–H functionalizations offer the
potential for superior site selectivities and chemoselectivities as compared to alternative approaches, enabling
the development of new, general C–H transformations. Our approach will involve the identification of new N-
functionalized reagents as well as innovative pathways in photoredox catalysis to unlock a diverse set of
valuable, currently inaccessible C–H transformations using heteroatom-centered radicals.
 Another major goal is to develop transition metal catalyzed processes for the stereoselective construction
of C–C bonds that would otherwise be challenging to accomplish. With few exceptions, the use of unactivated
alkyl halides in catalytic C–C bond-forming reactions involves reactive radical intermediates. This limitation
prevents the use of alkyl halides in stereoselective C–C bond-forming reactions that would streamline drug
synthesis and provide access to medicinally valuable, functionalized small molecules. We seek to establish
new paradigms in metal catalysis that enable the stereoselective direct coupling of unactivated alkyl
electrophiles and widely available chemical feedstocks. We hypothesize that two-electron activation of alkyl
electrophiles will unlock a range of stereoselective C–C constructions. Our objectives include the development
of stereospecific, carbonylative transformations and stereoselective carbocyclizations of unactivated alkyl
electrophiles. 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 involves underutilized modes of chemical reactivity to gene...

## Key facts

- **NIH application ID:** 9922930
- **Project number:** 5R35GM131708-02
- **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:** 2020
- **Award amount:** $495,983
- **Award type:** 5
- **Project period:** 2019-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9922930

## Citation

> US National Institutes of Health, RePORTER application 9922930, Innovative Transformations of Fundamental Synthetic Building Blocks (5R35GM131708-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9922930. Licensed CC0.

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