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

Hon Cheung Leung; Tsz Chun Lee; Wing-Tak Wong; Wai Chung Fu

doi:10.1002/adsc.202400826

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

Hon Cheung Leung
, Tsz Chun Lee
, Wing-Tak Wong
, Wai Chung Fu

Department of Chemistry

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

3 Citations (Scopus)

Abstract

R-22 gas (ClCF₂H) is utilized in continu-ous flow for the installation of CF₂H and CF₂Dgroups on heteroatoms. A judiciously designed flow system suppresses the intrinsic S_N2 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–CF₂Dproducts (X = S, O, N) is obtained with a shortresidence time of 5 minutes and scalability isdemonstrated. © 2024 Wiley-VCH GmbH

Original language	English
Pages (from-to)	4385-4391
Journal	Advanced Synthesis & Catalysis
Volume	366
Issue number	21
Online published	23 Jul 2024
DOIs	https://doi.org/10.1002/adsc.202400826
Publication status	Published - 5 Nov 2024

Funding

We thank the Research Grants Council of Hong Kong General Research Fund (GRF: 15302021), Croucher Foundation, The Hong Kong Polytechnic University (1-ZVTT) and City University of Hong Kong for financial support. We thank Dr. Pui-Kin So, Dr. Kenneth Yan and Dr. Chun-Ming Chan for their assistance with HRMS and NMR analysis.

Research Keywords

Deuteration
Difluoromethylation
Continuous Flow Synthesis
Heteroatoms
Flow chemistry

RGC Funding Information

RGC-funded

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10.1002/adsc.202400826

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Cite this

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title = "Rapid (Deuterio)difluoromethylation of Heteroatoms using R-22 Gas: A Demonstration of Flow Chemistry in Suppressing Intrinsic Reaction Pathways",

abstract = "R-22 gas (ClCF2H) is utilized in continu-ous flow for the installation of CF2H and CF2Dgroups 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–CF2Dproducts (X = S, O, N) is obtained with a shortresidence time of 5 minutes and scalability isdemonstrated. {\textcopyright} 2024 Wiley-VCH GmbH",

keywords = "Deuteration, Difluoromethylation, Continuous Flow Synthesis, Heteroatoms, Flow chemistry",

author = "Leung, \{Hon Cheung\} and Lee, \{Tsz Chun\} and Wing-Tak Wong and Fu, \{Wai Chung\}",

year = "2024",

month = nov,

day = "5",

doi = "10.1002/adsc.202400826",

language = "English",

volume = "366",

pages = "4385--4391",

journal = "Advanced Synthesis \& Catalysis",

issn = "1615-4150",

publisher = "Wiley-VCH Verlag GmbH",

number = "21",

}

Rapid (Deuterio)difluoromethylation of Heteroatoms using R-22 Gas: A Demonstration of Flow Chemistry in Suppressing Intrinsic Reaction Pathways. / Leung, Hon Cheung; Lee, Tsz Chun; Wong, Wing-Tak et al.
In: Advanced Synthesis & Catalysis, Vol. 366, No. 21, 05.11.2024, p. 4385-4391.

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

TY - JOUR

T1 - Rapid (Deuterio)difluoromethylation of Heteroatoms using R-22 Gas

T2 - A Demonstration of Flow Chemistry in Suppressing Intrinsic Reaction Pathways

AU - Leung, Hon Cheung

AU - Lee, Tsz Chun

AU - Wong, Wing-Tak

AU - Fu, Wai Chung

PY - 2024/11/5

Y1 - 2024/11/5

N2 - R-22 gas (ClCF2H) is utilized in continu-ous flow for the installation of CF2H and CF2Dgroups 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–CF2Dproducts (X = S, O, N) is obtained with a shortresidence time of 5 minutes and scalability isdemonstrated. © 2024 Wiley-VCH GmbH

AB - R-22 gas (ClCF2H) is utilized in continu-ous flow for the installation of CF2H and CF2Dgroups 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–CF2Dproducts (X = S, O, N) is obtained with a shortresidence time of 5 minutes and scalability isdemonstrated. © 2024 Wiley-VCH GmbH

KW - Deuteration

KW - Difluoromethylation

KW - Continuous Flow Synthesis

KW - Heteroatoms

KW - Flow chemistry

UR - https://www.scopus.com/pages/publications/85210103219

UR - https://www.scopus.com/record/pubmetrics.uri?eid=2-s2.0-85210103219&origin=recordpage

U2 - 10.1002/adsc.202400826

DO - 10.1002/adsc.202400826

M3 - RGC 21 - Publication in refereed journal

SN - 1615-4150

VL - 366

SP - 4385

EP - 4391

JO - Advanced Synthesis & Catalysis

JF - Advanced Synthesis & Catalysis

IS - 21

ER -

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

Abstract

Funding

Research Keywords

RGC Funding Information

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Front Cover Picture: Rapid (Deuterio)difluoromethylation of Heteroatoms Using R-22 Gas: A Demonstration of Flow Chemistry in Suppressing Intrinsic Reaction Pathways (Adv. Synth. Catal. 21/2024)

GRF: Design of “DFMA Tap” Continuous Flow System for Exploration and Application of Aminodifluoromethylation Chemistry Using Greenhouse Gases

Cite this

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

Abstract

Funding

Research Keywords

RGC Funding Information

Access Output

Other Access Options

Permanent Link

Other Files and Links

Fingerprint

Research output

Front Cover Picture: Rapid (Deuterio)difluoromethylation of Heteroatoms Using R-22 Gas: A Demonstration of Flow Chemistry in Suppressing Intrinsic Reaction Pathways (Adv. Synth. Catal. 21/2024)

Projects

GRF: Design of “DFMA Tap” Continuous Flow System for Exploration and Application of Aminodifluoromethylation Chemistry Using Greenhouse Gases

Cite this