Trimethyloxonium Tetrafluoroborate1

Me3O+BF4-

[420-37-1]  · C3H9BF4O  · Trimethyloxonium Tetrafluoroborate  · (MW 147.93)

(methylating agent;1 activates C-X multiple bonds;2 esterifies polyfunctional carboxylic acids;3 catalyst for polymerization of cyclic sulfides and ethers; Beckmann rearrangement of oximes4)

Physical Data: mp 179.6-180.0 °C (sealed tube, with dec).

Solubility: sol nitrobenzene, nitromethane, CHCl3, acetone (hot), SO2 (liq); slightly sol CH2Cl2; insol common organic solvents.

Form Supplied in: white crystalline solid; commercially available; is contaminated by ethyldimethyloxonium tetrafluoroborate.

Analysis of Reagent Purity: 1H NMR (CD2Cl2/SO2) d 4.68 (s, CH3); 13C NMR (CD2Cl2/SO2) d 78.8 (CH3).

Purification: highly pure oxonium salt is obtained from dimethoxycarbenium tetrafluoroborate and dimethyl ether.5 The resulting solid is vacuum dried at 50 °C/1 mmHg for 30 min.

Handling, Storage, and Precautions: when prepared according to Curphey,6 the oxonium salt is stable, nonhygroscopic, and may be readily handled in the air for short periods of time. The dry oxonium salt should be stored under argon at -15 °C or as a suspension in CH2Cl2 at -20 °C for prolonged periods. Batches stored in this manner for over a year have been successfully used for alkylations. Highly pure samples5 showed no change in spectral data after this time. Reactions of the reagent should be performed under an argon or a nitrogen atmosphere; dry solvents are also necessary. Because of its caustic nature and potent properties as an alkylating agent, direct contact with the skin must be avoided.

Functional Group Methylations.

The powerful alkylating property of trimethyloxonium tetrafluoroborate allows methylation of sensitive or weakly nucleophilic functional groups. Smooth alkylation of a variety of anions or uncharged molecules has been reported. Examples include carboxylic acids,7 ketones,2,8 lactones,4,9 nitriles,4,10 O-acetals,4 S-acetals,11 sulfoxides,12 sulfides,13 thioamides,14 thiophenes,13g and sulfonium ylides.14 As should be expected for strongly electrophilic agents,1c the hard oxonium salt yields considerable amounts of products derived from methylation at the site of the highest electron density (HSAB principle) when it reacts with ambident nucleophiles. O-Methylation of sulfoxides,15 N-methylation of sulfoximides,16 sulfinyl amines,17 sulfodiimides, and nitriles10 and S-methylation of thioamides14b have been observed. The very reactive cationic intermediates (e.g. carboxonium, carbosulfonium, or nitrilium ions) as primary products in those reactions are versatile intermediates for synthetic transformations. Ketones can be converted into a-acetoxy ketones via N-methylation of the oxime acetates (eq 1)18 and thioamides to amides (eq 2).14a,b

The reactions of thioacetals with Me3O+BF4- constitute a high-yielding method for deprotection of thioacetals to give ketones (eq 3).11a,19

The reagent has been employed as a quaternizing agent for a variety of N-heterocycles.20 Regioselective N-methylation has been observed (eq 4).20c Thiazoles are exclusively N-methylated,20a,b whereas tetrazoles yield regioisomeric products.20d,h The dication of squaric acid bis(amidine) is prepared by regioselective N-methylation (eq 5).21

1,3-Benzothiazolines react preferentially at nitrogen,22 whereas heterocycles containing dipolar carbonyl groups usually yield products resulting from O-methylation.2,23 Furthermore, Me3O+BF4- is the reagent of choice for the synthesis of higher alkylated products which are otherwise not obtainable. Examples are the preparation of vinylidene disulfonium salts (eq 6),13c dionium salts of N,S-13b and S,S-acetals,11a-c,24 or 1,4-dithianium ditetrafluoroborates (eq 7),19 and a heterocyclophane-type tetrasulfonium salt (eq 8). The latter introduces a hydrophobic cavity into the aqueous phase, thus serving as an inclusion catalyst.25

Trialkyloxonium salts such as Me3O+BF4- are excellent reagents for the generation of cyclopropenylium cations by O-methylation of suitable cyclopropenones (eq 9).26

The reaction of trialkyloxonium salts with carboxylic acids is a mild, general esterification procedure that does not require the use of more hazardous reagents such as Hexamethylphosphoric Triamide-Thionyl Chloride, Iodomethane, Dimethyl Sulfate, 3-Methyl-1-p-tolyltriazene, or Diazomethane. The reaction proceeds smoothly with sterically hindered acids, as well as with acids containing various functional groups such as amides or nitriles (eq 10).3,7

One of the major advantages of the use of oxonium salts is that alkylations can be effected under reaction conditions that are generally much milder than those necessary with conventional alkyl halides and sulfonates. Me3O+BF4- has been used as a suspension in CH2Cl2 or dichloroethane, or as a solution in nitromethane or liquid SO2. Alkylations in water27 and trifluoroacetic acid28 have been described, and direct fusion has been used in cases where other conditions failed.29 An SN2 mechanism must be assumed in the reaction of the reagent with nucleophiles. The rates of the complete hydrolysis decrease in the sequence Me3O+ >> Et3O+ > Pr3O+ > c-C5H10+OEt.30 Comparative studies on the alkylating ability of common methylating agents31 show that Me3O+ ions are more reactive than the trifluoromethanesulfonate ester (factor 5 to 12), following the order Me3O+ > MeOSO2CF3 > MeOSO2F > MeOClO3. In terms of availability, stability, and freedom from hazards, however, oxonium salts often appear the reagents of choice (including comparisons with other powerful alkylating agents such as dialkoxycarbenium ions,32 dialkylhalonium ions,33 and haloalkanes in the presence of silver salts34). While the carcinogenic properties of other potent alkylating agents are well documented,35 any such dangers associated with trialkyloxonium salts are presumably minimized by the fact that these compounds are water-soluble, nonvolatile, crystalline solids which are rapidly solvolyzed in aqueous solution.1b,36 Although Triethyloxonium Tetrafluoroborate is the cheaper and much more used oxonium salt in synthetic chemistry, Me3O+BF4- effects alkylations which the triethyl analog does not.11,37

Use in Transition Metal Chemistry.

Me3O+BF4- has been successfully used in the generation of transition metal carbene complexes by direct methylation of lithium acylcarbonylmetalates (eq 11).38 Oxidative addition processes by which metal-carbon s-bonds are formed have also been observed.39 Me3O+BF4- also serves as a halide acceptor in the reaction with square planar platinum(II) complexes.40

Catalytic Properties.

Me3O+BF4- has been used as a catalyst for the polymerization of cyclic sulfides and in the polymerization of THF to macrocyclic ethers.4 A valuable modern application is the catalytic Beckmann rearrangement of oximes in homogeneous liquid phase,41 the active species being a formamidinium salt.

Other Reactions.

The reaction of g-alkenyl-g-butyrolactones with allylsilanes in the presence of Me3O+BF4- as the lactone-activating agent is reported to proceed with high regio- and stereoselectivity to afford methyl (E)-4,8-alkadienoates in high yields (eq 12).42

Me3O+BF4- has also been used as a methylating agent of the lithium enolate of a b-keto sulfoxide, leading to a mixture of isomeric dienol ethers, which are of potential interest as substrates for asymmetric Diels-Alder cycloadditions (eq 13).43

Related Reagents.

Dimethyl Sulfate; Iodomethane.


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Ingfried Stahl

Universität Kassel, Germany



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