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

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

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Advances in the Synthetic Utility of Difluorocarbene Generated from TMSCF₃ (Ruppert‐Prakash Reagent) and Its Derivatives

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

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

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

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Tetrafluoroisopropylation of alkenes and alkynes enabled by photocatalytic consecutive difluoromethylation with CF2HSO2Na

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

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

Angewandte Chemie, Journal Year: 2024, Volume and Issue: 136(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

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Selective Installation of C1-C3 Fluorocarbons to Aldehydes

Synfacts, Journal Year: 2024, Volume and Issue: 20(03), P. 0314 - 0314

Published: Feb. 14, 2024

Key words fluorination - fluoroalkenes lipophilicity tuning

Language: Английский

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