Highly selective catalytic transfer hydrodeuteration of cyclic alkenes

Selective deuterium installation into small molecules is becoming increasingly desirable not only for the elucidation of mechanistic pathways and studying biological processes but also because of deuterium's ability to favorably adjust the pharmacokinetic parameters of bioactive molecules. Fuse...

Full description

Saved in:
Bibliographic Details
Published in:Journal of labelled compounds & radiopharmaceuticals 2023-03, Vol.66 (3), p.86-94
Main Authors: Hintzsche, Samuel J., Vang, Zoua Pa, Rivera Torres, Emanuel, Podoski, Mykaela, Clark, Joseph R.
Format: Article
Language:English
Subjects:
Alkenes
Alkenes - chemistry
Biological activity
Catalysis
Chemical bonds
Copper
Cycloparaffins
Deuteration
Deuterium
Deuterium - chemistry
hydrodeuteration
Hydrogen - chemistry
hydrogenation
Pharmacokinetics
Reagents
Regioselectivity
transition metal catalysis
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Selective deuterium installation into small molecules is becoming increasingly desirable not only for the elucidation of mechanistic pathways and studying biological processes but also because of deuterium's ability to favorably adjust the pharmacokinetic parameters of bioactive molecules. Fused bicyclic moieties, especially those containing heteroatoms, are prevalent in drug discovery and pharmaceuticals. Herein, we report a copper‐catalyzed transfer hydrodeuteration of cyclic and heterocyclic alkenes, which enables the synthesis of chromans, quinolinones, and tetrahydronaphthalenes that are precisely deuterated at the benzylic position. We also demonstrate the ability to place one deuterium atom at the homobenzylic site of these scaffolds with high regioselectivity by swapping transfer reagents for their isotopic analogs. Furthermore, examples of chemoselective transfer hydrogenation and transfer deuteration are disclosed, allowing for the simultaneous incorporation of two vicinal hydrogen or deuterium atoms into a double bond. We report a copper‐catalyzed installation of hydrogen and deuterium across cyclic alkenes that enables the synthesis of precisely deuterated chromanes, quinolinones, and tetrahydronaphthalenes. Swapping hydrogen and deuterium transfer reagents permits full control over the isotopic labeling pattern in the product and further expands the precision deuteration reaction toolbox.
ISSN:0362-4803
1099-1344
DOI:10.1002/jlcr.4015