(Trifluoromethyl)trimethylsilane

Introduction

(Trifluoromethyl)trimethylsilane (TMSCF₃) is a flammable liquid with a boiling point of 54–55 °C, a flash point of –17 °C and density of 0.926 g/mL at 20 °C. It may be harmful if inhaled, swallowed, absorbed through skin and may cause respiratory tract, skin and eye irritation. TMSCF₃ was firstly synthesized by Rupert[ ¹ ] in 1984 via the condensation reaction of CF₃Br and TMSCl with (Et₂N)₃P. Nowadays, there are various synthetic methodologies to yield this compound. Among them, the approach of Pawelke is considered as the most efficient method.[ ² ] Following this method, the reaction of CF₃I and tetrakis(dimethylamino)ethylene formed an in situ mediated complex which reacted directly with TMSCl to afford TMSCF₃ in 94% yield. TMSCF₃ is versatile reagent for trifluoromethylation, such as transition-metal-catalyzed reaction, miscellaneous trifluoromethylation, and addition to carbonyl and imine groups. These reactions are extremely useful approaches in the pharmaceutical and agrochemical industry,[ ³ ] because they enhance metabolic stability (metabolic blocking) and alter the compound properties (liphophilicity, binding selectivity).

Abstract

(A) Oxidative Trifluoromethylation of Terminal Alkynes and ­Heteroarenes: Qing and co-worker described a powerful method for the synthesis of a broad range of trifluoromethylated acetylenes in good yields by using the copper-mediated protocol.[ 4 ] Recently, they have developed an alternative copper-catalyzed trifluoromethylation.[ 5 ] This method is also applied to the oxidative trifluoromethylation of heteroarenes and highly electron-deficient arenes via C–H activation.[ 6 ]
(B) Oxidative Trifluoromethylation of Boronic Acids: Copper-mediated or -catalyzed oxidative cross-couplings of aryl- and alkenylboronic acids with TMSCF3 under mild condition have been reported.[5] [7] This procedure can be employed in the various ranges of functionalized aryl, heteroaryl and alkenyl boronic acids.
(C) Cu-Catalyzed Reaction of Arylboronic Acid with TMSCF3 ­and S8: This study provides an efficient and convenient protocol for the synthesis of aryl trifluoromethyl thioethers.[ 8 ]
(D) Cu-Mediated Nucleophilic Trifluoromethylation of Allyl Halides: The trifluoromethylated allylic products have been synthesized in good yields.[ 9 ]
(E) Ag-Mediated Trifluoromethylation of Arenes: The innovative procedures for silver-mediated CH trifluoromethylation of aromatic substrates were developed by Melanie S. Sanford and co-workers.[ 10 ] The mechanism of these reactions is suggested to proceed via an AgCF3 intermediate.
(F) Pd-Catalyzed Trifluoromethylation of Aryl Halides and Vinyl Sulfonates: Hartwig,[ 11 ] Sanford,[ 12 ] Grushin[ 13 ] and Buchwald[14] [15] have contributed to a notable feature of this reaction.
(G) Pd-Catalyzed Intermolecular Oxidative Aryltrifluoromethylation of Activated Alkenes: The powerful synthesis of oxidole derivatives containing CF3 was explored by Liu and colleagues.[ 16 ] The desired products were obtained via initial arylpalladation of alkenes, continued by sequential oxidation and reductive elimination of Csp2 PdIVCF3 species.
(H) Synthesis of α-CF3 N-Heterocycles Through Tandem Nucleophilic Additions: A powerful strategy for the synthesis of precursors of biologically important unnatural cyclic amino acids and fluorinated N-heterocycles by tandem reactions based on amination and trifluoromethylation catalyzed by AgF was reported by Hammond.[ 17 ]
(I) Addition to the Carbonyl Group: The catalytic nucleophilic enantioselective trifluoromethylation of carbonyls, including aldehydes,[ 18 ] ketones[ 18 ] (alkynylketones[ 19 ] and aryl ketones[ 20 ]), acyltrifluoromethane,[ 21 ] acylphosphonates[ 22 ] and acylsilanes[23] [24] was reported. The addition to related carbonyl compounds (enones, amides, esters sulfonic, sulfinic, selenic esters and α-keto esters) was also described.[ 18 ]
(J) Addition to Imines, Nitrones, Thiocyanate and Selenocyante: This series of trifluoromethylation by addition allows for generating promising candidates for the pharmaceutical and agrochemical industry.[ 18 ]

• References

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