# Inverting Coupling Selectivity with Cooperative Metal-Ligand Constructs

> **NIH NIH R21** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2020 · $136,914

## Abstract

PROJECT SUMMARY/ABSTRACT
Advances in catalytic science and technology enable the preparation of pharmaceutical agents used to
treat human disease. Catalytic cross coupling reactions are among the most commonly employed reac-
tions for the assembly of drugs and drug candidates in the pharmaceutical industry. Aryl ethers and fluo-
rides are common intermediates in synthesis, but they are still considered to be challenging electrophiles
for catalytic cross coupling. Catalytic methods that open this class of electrophile to cross coupling and
allow their selective functionalization would significantly aid in the preparation of bioactive small mole-
cules. This exploratory research project has the goal of developing a new technology for strong bond ac-
tivation that will enable broad advances in catalytic cross coupling reactions of recalcitrant substrates.
The first major milestone will be to establish the stoichiometric activation of aryl C–O and C–F bonds
across metal-ligand cooperative constructs and to realize catalytic cross coupling of these electrophiles.
The second major milestone will be to achieve selective activation of C–O and C–F substrates in the
presence of other functionalizable moieties. The proposed research is expected to yield new practical
catalytic methods for the construction of pharmacologically-relevant small molecules that meet the chal-
lenges of selective synthesis. Also, the research will establish a new technology for catalytic coupling
based on the conceptualization of metal-ligand constructs as cooperative functional engines for bond
making and breaking. Taken together, these outcomes will transform the practice of catalytic strong bond
activation by the introduction of a new and powerful modality in homogeneous catalysis.

## Key facts

- **NIH application ID:** 9984419
- **Project number:** 5R21GM134240-02
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** ALEXANDER T RADOSEVICH
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $136,914
- **Award type:** 5
- **Project period:** 2019-08-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984419

## Citation

> US National Institutes of Health, RePORTER application 9984419, Inverting Coupling Selectivity with Cooperative Metal-Ligand Constructs (5R21GM134240-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9984419. Licensed CC0.

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