1.6 Synthesis of Difluoromethylated Compounds DOI
Simin Wu, Hayeon Song, Mingyou Hu

et al.

Published: Jan. 1, 2024

Abstract The difluoromethyl group (CF2H) can function as a lipophilic hydrogen-bond donor, and is regarded bioisostere of functional groups such hydroxy (-OH), thiol (-SH), amino (-NH2). unique physicochemical properties this make difluoromethylation hot topic in the field synthetic organic chemistry, recent decades, various methods have been developed for constructing C(sp3)—CF2H, C(sp2)—CF2H, C(sp) —CF2H, X—CF2H (X = N, O, S, Se, B, P, etc.) bonds. This review summarizes currently available reagents performing reactions, well other approaches installing unit.

Language: Английский

A Journey of the Development of Privileged Difluorocarbene Reagents TMSCF2X (X = Br, F, Cl) for Organic Synthesis DOI
Qiqiang Xie, Jinbo Hu

Accounts of Chemical Research, Journal Year: 2024, Volume and Issue: 57(5), P. 693 - 713

Published: Feb. 14, 2024

ConspectusAs fluorine has played an increasingly important role in modulating the physical, chemical, and biological properties of organic molecules, selective introduction atom(s) or fluorinated moieties into target molecules become a powerful tool development new pharmaceuticals, agrochemicals, functional materials. In this context, difluoromethylene (CF2) difluoromethyl (CF2H) groups are special interest because their ability to serve as bioisosteres ethereal oxygen atoms hydroxyl (OH) thiol (SH) groups, respectively. Difluorocarbene is one most versatile reactive intermediates incorporate CF2 CF2H groups; however, before 2006, previously known difluorocarbene reagents suffered from several drawbacks such using ozone-depleting substances (ODSs), difficult-to-handle reagents, harsh reaction conditions having narrow substrate scope and/or low yields. Moreover, reactivity generated different precursors (reagents) was often unpredictable, since generation (activation modes) various different, these may mismatch those required for subsequent difluorocarbene-involved transformations. Therefore, environmentally friendly well investigation mechanistic insights reactions, been highly desirable.In Account, we summarize our contributions applications synthesis 2006. We have developed seven including 2-chloro-2,2-difluoroacetophenone (1), chlorodifluoromethyl phenyl sulfone (2), S-difluoromethyl-S-phenyl-N-tosylsulfoximine (3), difluoromethyltri(n-butyl)ammonium chloride (4), (chlorodifluoromethyl)trimethylsilane (TMSCF2Cl, 5), (bromodifluoromethyl)trimethylsilane (TMSCF2Br, 6), (trifluoromethyl)trimethylsilane (TMSCF3, 7). journey, realized key factor ideal reagent that can be used broad range is, should allow activation modes species, under basic/acidic/neutral conditions, at wide temperatures, solvents, which compatible with Among all silanes TMSCF2X (X = Br, F, Cl) stood out privileged ones, paves avenue further developing chemistry. particular, TMSCF2Br recognized "all-rounder": applied almost common more importantly, also enables many other novel transformations cannot achieve, thanks its unique structure rich releasing conditions. It expected commercial availability now, chemistry will accelerated years come.

Language: Английский

Citations

21
Controllable Fluorocarbon Chain Elongation: TMSCF2Br-Enabled Trifluorovinylation and Pentafluorocyclopropylation of Aldehydes DOI
An Liu, Xianghong Zhang, Feng Zhao

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(3), P. 1806 - 1812

Published: Jan. 9, 2024

Controllable fluorocarbon chain elongation (CFCE) is a promising yet underdeveloped strategy for the well-defined synthesis of structurally novel polyfluorinated compounds. Herein, direct and efficient trifluorovinylation pentafluorocyclopropylation aldehydes are described by using TMSCF

Language: Английский

Citations

6
Catalytic Asymmetric Difluoroalkylation Using In Situ Generated Difluoroenol Species as the Privileged Synthon DOI Creative Commons

Xiongda Xie,

Shanliang Dong,

Kemiao Hong

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(14)

Published: Feb. 6, 2024

A robust and practical difluoroalkylation synthon, α,α-difluoroenol species, which generated in situ from trifluoromethyl diazo compounds water the presence of dirhodium complex, is disclosed. As compared to presynthesized difluoroenoxysilane formed difluoroenolate under basic conditions, this difluoroenol intermediate displayed versatile reactivity, resulting dramatically improved enantioselectivity mild conditions. demonstrated catalytic asymmetric aldol reaction Mannich reactions with ketones or imines chiral organocatalysts, quinine-derived urea, phosphoric acid (CPA), respectively, relay catalysis strategy provides an effective platform for applying fluorination chemistry. Moreover, method features a novel 1,2-difunctionalization process via installation carbonyl motif alkyl group on two vicinal carbons, complementary protocol metal carbene gem-difunctionalization reaction.

Language: Английский

Citations

6
Difluorocarbene-induced [1,2]- and [2,3]-Stevens rearrangement of tertiary amines DOI Creative Commons

Jianke Su,

Yu Guo, Chengbo Li

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: June 5, 2024

The [1,2]- and [2,3]-Stevens rearrangements are one of the most fascinating chemical bond reorganization strategies in organic chemistry, they have been demonstrated a wide range applications, representing fundamental reaction tactic for synthesis nitrogen compounds community. However, their applicabilities limited by scarcity efficient, general, straightforward methods generating ammonium ylides. Herein, we report general difluorocarbene-induced tertiary amine-involved stemmed from situ generated difluoromethyl ylides, which allows versatile amines bearing either allyl, benzyl, or propargyl groups, resulting corresponding products under same conditions with way. Broad substrate scope, simple operation, mild late-stage modification natural highlight advantages this strategy, meanwhile, rearrangement is believed to bring opportunities transformations ylides assembly valuable amino acids. This will further enrich repertoire difluorocarbene species, facilitate development reactions involving salts, provide an avenue type reactions.

Language: Английский

Citations

6
Visible Light-Induced Radical Cascade Difluoromethylation/Cyclization of Unactivated Alkenes: Access to CF2H-Substituted Polycyclic Imidazoles DOI Creative Commons
S.J. Lin, Yuanyuan Deng,

Hanxun Zhong

et al.

ACS Omega, Journal Year: 2024, Volume and Issue: 9(26), P. 28129 - 28143

Published: June 19, 2024

An efficient and mild protocol for the visible light-induced radical cascade difluoromethylation/cyclization of imidazoles with unactivated alkenes using easily accessible bench-stable difluoromethyltriphenylphosphonium bromide as precursor -CF

Language: Английский

Citations

5
Advances in the Synthetic Utility of Difluorocarbene Generated from TMSCF3 (Ruppert‐Prakash Reagent) and Its Derivatives DOI Open Access
Jagadeesh Krishnan,

K. Reyaz Ali Sahib,

Keerthana G. Nair

et al.

The Chemical Record, Journal Year: 2025, Volume and Issue: unknown

Published: March 12, 2025

Abstract Organofluorine compounds are of pivotal significance particularly, in drug and agrochemical industries different strategies have been designed for their synthesis. The last two decades witnessed the emergence difluorocarbene as an efficient synthetic tool, providing easy access to organofluorine compounds. This review summarises reactions generated from Ruppert‐Prakash reagent (TMSCF 3 ) its derivatives TMSCF 2 Cl Br. Among various fluorination techniques available, chemistry offers a cost effective procedure, opening avenue large number details developments utility derivatives, till date.

Language: Английский

Citations

0
Visible Light-Promoted Defluorinative Alkylation of Trifluoromethyl Ketones with α-Aminoalkyl Boron Species DOI
Yue Zhang, Kun Li, Zhihong Wang

et al.

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: April 14, 2025

In this study, we developed a photoredox-catalyzed defluorinative cross-coupling method for trifluoroketones and alkyl boronic acids. The reaction afforded series of novel α,α-difluoroketone derivatives, in vitro fungicidal activity revealed that some these compounds exhibited moderate to excellent against Rhizoctonia solani Botrytis cinerea. particular, compound 3d showed an EC50 value 4.27 μg/mL B. cinerea can be used as lead further optimization.

Language: Английский

Citations

0
Divergent Generation of the Difluoroalkyl Radical and Difluorocarbene via Selective Cleavage of C–S Bonds of the Sulfox-CF2SO2Ph Reagent DOI

Shuyao Li,

Xiu Wang, Yide Yang

et al.

Organic Letters, Journal Year: 2024, Volume and Issue: 26(4), P. 872 - 876

Published: Jan. 18, 2024

A new difluoroalkylation reagent Sulfox-CF2SO2Ph bearing both sulfoximine and sulfone moieties was prepared from commercially available SulfoxFluor PhSO2CF2H. On one hand, the could act as a (phenylsulfonyl)difluoromethyl radical source under photoredox catalysis, in which arylsulfoximidoyl group is selectively removed. other basic conditions, serve difluorocarbene precursor for S- O-difluoromethylations with O-nucleophiles, respectively, phenylsulfonyl removed (followed by α-elimination of group).

Language: Английский

Citations

3
Tetrafluoroisopropylation of alkenes and alkynes enabled by photocatalytic consecutive difluoromethylation with CF2HSO2Na DOI Creative Commons

Yuwei Hong,

Jiayan Qiu,

Zhenhua Wu

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: July 6, 2024

Direct assembly of complex fluorinated motifs from simple fluorine sources is an attractive frontier synthetic chemistry. Reported herein unconventional protocol for achieving tetrafluoroisopropylation by using commercially available CF

Language: Английский

Citations

3
Controllable Double Difluoromethylene Insertions into S−Cu Bonds: (Arylthio)tetrafluoroethylation of Aryl Iodides with TMSCF2Br DOI

Shitao Pan,

Qiqiang Xie, Xiu Wang

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(14)

Published: Feb. 15, 2024

Abstract A new method of constructing “ArSCF 2 CF Cu” from ArSCu and TMSCF Br (TMS=trimethylsilyl) has been developed. The cross‐coupling reactions the obtained with diverse aryl iodides (Ar′I) provide an efficient access to Ar′CF SAr. Mechanistic studies demonstrate that species were generated through controllable double difluoromethylene insertions into ArS−Cu bonds rather than 1,2‐addition tetrafluoroethylene.

Language: Английский

Citations

2