# Regio- and Enantioselective Alkene Difunctionalizations for the Synthesis of Bioactive Molecules.

> **NIH NIH R15** · UNIVERSITY OF TOLEDO · 2020 · $451,500

## Abstract

Project Summary/Abstract
Chiral β-amino functionalized molecules are common motifs often found in a variety of saturated heterocycles
of important drug molecules. They are also ubiquitous chiral building blocks in organic synthesis to access, for
example, chiral oxazoline-based ligands that are broadly useful in asymmetric catalysis. The functional
importance of these molecules renders their syntheses continuously in high demand. Alkene difunctionalization
represents a highly modular strategy towards these structural motifs as benchmarked by the venerable
osmium-catalyzed protocols developed by Sharpless and coworkers. However, significant challenges remain
for this class of reactions. The main objective of this program is to develop new classes of catalytic alkene
difunctionalizations that will meet the demands of these challenges and expedite access to chiral β-amino
functionalized motifs. Specifically, this proposal will introduce halonium and hypervalent iodine catalysis as
platforms to resolve the regiochemical and enantioselective challenges often encountered in these reactions.
Based on solid preliminary data, the proposed studies will enable us to: 1) demonstrate the feasibility of
nucleophile-control for regiochemical control in halonium catalysis with a range of bifunctional nucleophiles; 2)
utilize hypervalent iodine catalysts as a new element for regiocontrol in alkene difunctionalizations; and 3)
adopt chiral hypervalent iodine catalyst for asymmetric induction of the reactions proposed. Our proposal is
innovative by introducing several means of regiocontrol and asymmetric induction based on a single
elementary step. Additionally, these methods use simple and ubiquitous bifunctional reagents such as amide,
urea, carbamate, etc. for alkene difunctionalizations. Finally, realization of the proposed strategy will enable
straightforward synthesis of chiral β-amino functionalized motifs.

## Key facts

- **NIH application ID:** 10046958
- **Project number:** 1R15GM139156-01
- **Recipient organization:** UNIVERSITY OF TOLEDO
- **Principal Investigator:** Wei Li
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $451,500
- **Award type:** 1
- **Project period:** 2020-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10046958

## Citation

> US National Institutes of Health, RePORTER application 10046958, Regio- and Enantioselective Alkene Difunctionalizations for the Synthesis of Bioactive Molecules. (1R15GM139156-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10046958. Licensed CC0.

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