# Aliphatic Effects in Transition Metal Catalysis

> **NIH NIH R35** · UNIVERSITY OF HOUSTON · 2020 · $381,329

## Abstract

Project Summary. An incredible diversity of transition metal-catalyzed methods has been
developed around a small subset of elementary organometallic reactions. The overarching
goal of our research program is to expand this tool box to include new organometallic
mechanisms that can in turn be integrated into many new catalytic transformations to
generate new organic structures. A central hypothesis of this proposal is that enforcing
persistent coordinative-unsaturation in catalyst structures can enable unique
organometallic mechanisms, such as in the transmetalation step common to all carbon-
carbon and carbon-heteroatom cross-coupling reactions – some of the most practiced
reactions at all levels of pharmaceutical research. Our approach is inspired by the potential
for substantial attractive van der Waals forces in large aliphatic groups, which we are able to
incorporate into metal catalysts structures using large organophosphorus ligands. A primary
focus of this work will be to understand the mechanisms of, and to leverage, an unusual
series of transmetalation reactions we have observed with mixtures of low-coordinate
palladium complexes and protic nucleophiles, such as organoboronic acids. These reactions
can occur under very mild conditions even in the absence of strong base, which has been
historically necessary in many cross-coupling reactions yet also compromises the
compatibility with sensitive compounds. The unique influence of diamondoids, such as in
tri(1-adamantyl)phosphine, in promoting this chemistry may reflect the large polarizability
and dispersion forces manifested in large aliphatic molecules. In order to generalizing these
aliphatic effects, we will concurrently pursue new, modular methods to construct congested
C(sp3)−P bonds, which are common motifs in both catalytic structures and also many
biologically active compounds. Furthermore, we will expand these aliphatic effects to
promote historically challenging transmetalation and oxidative addition reactions in iron and
copper catalysis, respectively, which are general problems that have hindered efforts
hindered to develop more sustainable cross-coupling methods using abundant base metals
Together the catalytic and organophosphorus synthetic efforts of this proposal will generate
new biologically active molecular structures through novel carbon-element bond forming
reactions.

## Key facts

- **NIH application ID:** 10438945
- **Project number:** 7R35GM128902-04
- **Recipient organization:** UNIVERSITY OF HOUSTON
- **Principal Investigator:** Bradley Carrow
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $381,329
- **Award type:** 7
- **Project period:** 2018-07-15 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10438945

## Citation

> US National Institutes of Health, RePORTER application 10438945, Aliphatic Effects in Transition Metal Catalysis (7R35GM128902-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10438945. Licensed CC0.

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