electrochemical dication pool: a new strategy to couple alkenes and abundant nucleophiles

NIH RePORTER · NIH · R01 · $302,391 · view on reporter.nih.gov ↗

Abstract

PROJECT SUMMARY/ABSTRACT Oxidative alkene functionalization reactions are a fundamental class of organic reactions. These reactions are valuable because they transform readily accessible alkene starting materials into diverse polar functional groups. However, the design strategies that underpin conventional alkene oxidation reactions require electrophilic reagents that serve as both the oxidant and the source of the newly installed functional group. This substantially limits the chemical diversity accessible using these methodologies. A modular approach to alkene oxidation that directly leverages abundant nucleophiles is a long-standing challenge with no general solutions. This proposal is based on a recent discovery from my group that electrochemistry can generate a new class of dicationic adducts between alkenes and thianthrene that are exceptionally selective dielectrophiles. We will study how these adducts can be exploited to develop a suite of alkene oxidation reactions that are otherwise infeasible with modern synthetic tactics. The three specific aims of this research explore distinct but interwoven aspects of this new reaction platform. Aim 1. We are advancing a strategy for strained ring synthesis from abundant precursors Aim 2. We are advancing a modular platform for oxidative alkene heterodifunctionalization Aim 3. We are advancing a strategy for allylic amine synthesis from abundant precursors The methods developed through this work each address long-standing challenges in a fundamental class of organic reactions, alkene oxidations. These new reaction protocols will offer an expanded and diversified pool of building blocks from which the next generation of drugs and molecular probes will be discovered.

Key facts

NIH application ID
10904656
Project number
5R01GM149674-02
Recipient
UNIVERSITY OF WISCONSIN-MADISON
Principal Investigator
Zachary Kimble Wickens
Activity code
R01
Funding institute
NIH
Fiscal year
2024
Award amount
$302,391
Award type
5
Project period
2023-08-15 → 2027-05-31