# Catalytic Asymmetric Hydroboration: Uncapping the Potential with Two-Point Binding Substrates

> **NIH NIH R01** · UNIVERSITY OF NEBRASKA LINCOLN · 2020 · $309,925

## Abstract

Project Summary/Abstract. Catalytic Asymmetric Hydroboration: Uncapping the Potential with Two-
Point Binding Substrates
Developing efficient methods for the reliable, stereocontrolled synthesis of small molecules via asymmetric
catalysis is central to providing the means to prepare potential mechanistic probes and pharmaceuticals.
These are essential tools that enable the better understanding and control of biological processes relevant to
human health. The development of new catalytic asymmetric reactions is therefore of both practical and
fundamental importance to the NIH mission.
Chiral organoboranes are finding increasing use as synthetic intermediates en route to other useful
functionality via stereospecific functional group interconversion, as reagents for asymmetric synthesis, and
synthetic targets for pharmaceutical applications. The stereochemistry of the carbon-boron bond is exploited
via stereospecific transmetallation or conversion to other useful functional groups. Organoboranes are
therefore seen as important intermediates for incorporating a variety of functional groups with defined
stereochemistry in natural product, pharmaceutical intermediate, and materials synthesis. Recent
breakthroughs in the development of methods for the stereospecific conversion of carbon-boron to carbon-
carbon bonds increase the demand for efficient methods to synthesize chiral organoboronates.
The proposed studies build on recent breakthroughs in the CAHB of two-point binding substrates. The key
innovation is in focusing on the directed CAHB of two-point binding substrates leading to successful catalysts
derived from simple, readily accessible monodentate phosphite and phosphoramidite ligands. This is in
contrast to prior approaches that focused on a more limited range of substrates, i.e., vinylarenes or strained
alkenes, using catalysts employing more complex, chelating ligands. The specific aims of the proposal are to
(i) expand the scope of directed-CAHB by: building on the results obtained for regio- and enantioselective
borylation of β,γ-unsaturated substrates; building on promising preliminary results for substrates in which the
directing group is further removed from the alkene; and further developing an understanding of the mechanism
and the potential for enhanced regiocontrol and (ii) expand the scope of transformations stemming from
interrupted-CAHB catalysis by: expanding the substrate scope for borane-promoted, rhodium-catalyzed
catalytic asymmetric hydrogenation (CAH); further delineating the mechanism of a borane-promoted CAH via
interrupted CAHB; and expanding to other metal catalyst systems and exploring other ways to exploit the
reactivity of the presumed metal-boryl intermediates generated by CAHB. A greater variety of chiral
organoboronates will be made readily available as a result of this project.

## Key facts

- **NIH application ID:** 9964839
- **Project number:** 5R01GM100101-08
- **Recipient organization:** UNIVERSITY OF NEBRASKA LINCOLN
- **Principal Investigator:** JAMES M TAKACS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $309,925
- **Award type:** 5
- **Project period:** 2012-05-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9964839

## Citation

> US National Institutes of Health, RePORTER application 9964839, Catalytic Asymmetric Hydroboration: Uncapping the Potential with Two-Point Binding Substrates (5R01GM100101-08). Retrieved via AI Analytics 2026-07-20 from https://api.ai-analytics.org/grant/nih/9964839. Licensed CC0.

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