# Simplifying Synthesis Through Base Metal Catalysis

> **NIH NIH R01** · TRUSTEES OF INDIANA UNIVERSITY · 2020 · $278,847

## Abstract

Project Abstract
Chemists need more reliable, concise methods for accessing structural complexity. Decreasing the time to
optimize the properties of a compound en route to the clinic requires reactions that are compatible with drug-
like structures. Many state-of-the-art catalytic reactions based on the noble metals require highly specialized
conditions and exotic ligands while remaining incompatible with common Lewis basic sites found in clinical
candidates. In contrast, base metal catalysis, although vastly less developed, is ideally suited to overcome
these issues through their rapid stepwise oxidative addition that enables facile Csp3-based cross couplings.
Moreover, base metals offer long-term sustainability, low costs, and superior environmental profiles relative to
their noble metal counterparts. Despite this potential, only small, isolated efforts exist to establish and explore
the reactivity of base metals in cross-coupling processes. The goal of the laboratory is to develop and
understand new synthetic strategies that enable the straightforward construction of complex molecules. The
objective of this application is to invent different classes of base metal-catalyzed cross-coupling reactions that
provide access to new reagents, pharmacophores, and SAR opportunities for medicinal chemistry. The
rationale for developing the proposed chemistry is that it will offer new avenues for the late-stage
functionalization of drug-like molecules as well as access to new chemical matter. With the benefit of robust
preliminary data, the goals will be pursued under two specific aims: 1) manganese-catalyzed borylation of alkyl
chlorides; and 2) 1,2-difunctionalization of alkenes. Under the first aim, novel manganese systems will be used
to address key gaps in the synthesis of complex alkyl boronates from alkyl halides, leading to new boron-
containing structures for drug discovery. Under the second aim, a new route to the 1,2-carboboration and 1,2-
carboarylation of alkenes will offer unique regioselectivity and provide access to new fluorinated compounds,
biologically active molecules, and opportunities in late-stage functionalization of drug-like molecules. Both of
the proposed aims target transformations that are not currently possible. The conversion of ubiquitous
functional groups (halides and alkenes) into complex functionality allows the direct synthesis of key
pharmaceutical intermediates, drugs, and biological tool molecules.

## Key facts

- **NIH application ID:** 9920741
- **Project number:** 5R01GM121840-04
- **Recipient organization:** TRUSTEES OF INDIANA UNIVERSITY
- **Principal Investigator:** Silas P Cook
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $278,847
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9920741

## Citation

> US National Institutes of Health, RePORTER application 9920741, Simplifying Synthesis Through Base Metal Catalysis (5R01GM121840-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9920741. Licensed CC0.

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