Rapid (Deuterio)difluoromethylation of Heteroatoms Using R‐22 Gas: A Demonstration of Flow Chemistry in Suppressing Intrinsic Reaction Pathways

R‐22 gas (ClCF2H) is utilized in continuous flow for the installation of CF2H and CF2D groups on heteroatoms. A judiciously designed flow system suppresses the intrinsic SN2 reaction between heteroatom anions and ClCF2H, allowing for selective carbene‐based fragment coupling to yield X‐CF2D products...

Full description

Saved in:
Bibliographic Details
Published in:Advanced synthesis & catalysis 2024-11, Vol.366 (21), p.4385-4391
Main Authors: Leung, Hon Cheung, Lee, Tsz Chun, Wong, Wing‐Tak, Fu, Wai Chung
Format: Article
Language:English
Subjects:
Chemical reactions
Continuous flow
Continuous flow synthesis
Deuteration
Deuterium
Difluoromethylation
Flow chemistry
Heteroatoms
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:R‐22 gas (ClCF2H) is utilized in continuous flow for the installation of CF2H and CF2D groups on heteroatoms. A judiciously designed flow system suppresses the intrinsic SN2 reaction between heteroatom anions and ClCF2H, allowing for selective carbene‐based fragment coupling to yield X‐CF2D products with deuterium incorporation levels up to 96%. A broad scope of X–CF2H and X–CF2D products (X=S, O, N) is obtained with a short residence time of 5 minutes and scalability is demonstrated.
ISSN:1615-4150
1615-4169
DOI:10.1002/adsc.202400826