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

Research output: Journal article publication › Journal article › Academic research › peer-review

2 Citations (Scopus)

Abstract

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 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–CF₂D products (X=S, O, N) is obtained with a short residence time of 5 minutes and scalability is demonstrated.

Original language	English
Pages (from-to)	4385-4391
Number of pages	7
Journal	Advanced Synthesis and Catalysis
Volume	366
Issue number	21
DOIs	https://doi.org/10.1002/adsc.202400826
Publication status	Published - 23 Jul 2024

Keywords

Continuous flow synthesis
Deuteration
Difluoromethylation
Flow chemistry
Heteroatoms

ASJC Scopus subject areas

Catalysis
Organic Chemistry

More information

10.1002/adsc.202400826

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 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.",

keywords = "Continuous flow synthesis, Deuteration, Difluoromethylation, Flow chemistry, Heteroatoms",

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

note = "Publisher Copyright: {\textcopyright} 2024 Wiley-VCH GmbH.",

year = "2024",

month = jul,

day = "23",

doi = "10.1002/adsc.202400826",

language = "English",

volume = "366",

pages = "4385--4391",

journal = "Advanced Synthesis and Catalysis",

issn = "1615-4150",

publisher = "Wiley-VCH Verlag",

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 and Catalysis, Vol. 366, No. 21, 23.07.2024, p. 4385-4391.

Research output: Journal article publication › Journal article › Academic research › peer-review

TY - JOUR

T1 - Rapid (Deuterio)difluoromethylation of Heteroatoms Using R-22 Gas: 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 - 2024/7/23

Y1 - 2024/7/23

N2 - 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.

AB - 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.

KW - Continuous flow synthesis

KW - Deuteration

KW - Difluoromethylation

KW - Flow chemistry

KW - Heteroatoms

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

U2 - 10.1002/adsc.202400826

DO - 10.1002/adsc.202400826

M3 - Journal article

AN - SCOPUS:85210103219

SN - 1615-4150

VL - 366

SP - 4385

EP - 4391

JO - Advanced Synthesis and Catalysis

JF - Advanced Synthesis and Catalysis

IS - 21

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

More information

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