Dimethoxycarbenium Tetrafluoroborate1

(1; R1 = Me, R2 = H, X = BF4)

[18346-68-4]  · C3H7BF4O2  · Dimethoxycarbenium Tetrafluoroborate  · (MW 161.89) (2; R1 = Me, R2 = H, X = Br)

[70146-62-2]  · C3H7BrO2  · Dimethoxycarbenium Bromide  · (MW 154.99) (3; R1 = Me, R2 = H, X = SbCl6)

[27434-62-4]  · C3H7Cl6O2Sb  · Dimethoxycarbenium Hexachloroantimonate  · (MW 409.56) (4; R1 = Me, R2 = H, X = PF6)

[50318-32-6]  · C3H7F6O2P  · Dimethoxycarbenium Hexafluorophosphate  · (MW 220.05) (5; R1 = Me, R2 = H, X = SbF6)

[66226-85-5]  · C3H7F6O2Sb  · Dimethoxycarbenium Hexafluoroantimonate  · (MW 310.83) (6; R1 = Et, R2 = H, X = BF4)

[1478-41-7]  · C5H11BF4O2  · Diethoxycarbenium Tetrafluoroborate  · (MW 189.94) (7; R1 = Me, R2 = Et, X = BF4)

[64950-83-0]  · C5H11BF4O2  · Dimethoxy(ethyl)carbenium Tetrafluoroborate  · (MW 189.94) (8; R1 = Et, R2 = H, X = SbCl6)

[1663-59-8]  · C5H11Cl6O2Sb  · Diethoxycarbenium Hexachloroantimonate  · (MW 437.61) (9; R1 = Et, R2 = H, X = PF6)

[97632-94-5]  · C5H11F6O2P  · Diethoxycarbenium Hexafluorophosphate  · (MW 248.10) (10; R1 = Et, R2 = Me, X = BF4)

[21872-75-3]  · C6H13BF4O2  · Diethoxy(methyl)carbenium Tetrafluoroborate  · (MW 203.97) (11; R1 = allyl, R2 = H, X = BF4)

[18346-72-0]  · C7H11BF4O2  · Diallyloxycarbenium Tetrafluoroborate  · (MW 213.97) (12; R1 = n-Pr, R2 = H, X = BF4)

[18346-70-8]  · C7H15BF4O2  · Diisopropoxycarbenium Tetrafluoroborate  · (MW 218.00) (13; R1 = i-Pr, R2 = H, X = BF4)

[18346-71-9]  · C7H15BF4O2  · Dipropoxycarbenium Tetrafluoroborate  · (MW 218.00) (14; R1 = Me, R2 = Ph, X = BF4)

[878-36-4]  · C9H11BF4O2  · Dimethoxy(phenyl)carbenium Tetrafluoroborate  · (MW 237.99) (15; R1 = Et, R2 = Ph, X = BF4)

[70861-63-1]  · C11H15BF4O2  · Diethoxy(phenyl)carbenium Tetrafluoroborate  · (MW 266.04) (16; R1 = Me, R2 = 2,4,6-Me3C6H2, X = BF4)

[15655-62-6]  · C12H17BF4O2  · Dimethoxy(mesityl)carbenium Tetrafluoroborate  · (MW 280.07)

(ambident electrophiles;1,2 alkylation of S-,3,4 N-,5 and O-nucleophiles;6,7 acylation of C-nucleophiles8)

Physical Data: mp: (1) 20 °C; (4) 72 °C; (6) 20 °C; (8) 151-152 °C; (10) 55 °C; (14) 88-90 °C; (15) dec; (16) 89-91 °C.

Solubility: freely sol liquid sulfur dioxide and arsenic trifluoride.9b,c When prepared in situ, halogenated solvents such as dichloromethane or 1,1,2-trichlorotrifluoroethane are most commonly used.2,5b,6a,b,8e,f With these solvents, however, the reagents are only slightly soluble and usually exist as a slurry at -30 °C. Refer to Olah et al.,9a where solubilities follow the trend phosphates > antimonates > borates.

Form Supplied in: the reagents are prepared in situ. They exist as colorless solids when isolated.6d Stability of the carbenium ions varies considerably, especially in the substituted analogs.6,8e,8f

Preparative Methods: each reagent is conveniently prepared by introduction of the desired Lewis acid such as Boron Trifluoride Etherate, Antimony(III) Chloride, or phosphorus pentafluoride to a cooled solution containing the appropriate orthoformate (or orthoester, R2 &neq; H).2 For dimethoxycarbenium bromide, the use of sulfur dioxide at -30 °C is required.9b For isolation techniques using a specially designed apparatus, see Pindur and Flo.10

Purification: since the reagents are prepared in situ, they are commonly used without further purification. When isolable, the reagents are purified by recrystallization.

Handling, Storage, and Precautions: dialkoxycarbenium salts are hygroscopic and should therefore be kept under an inert atmosphere (Ar or N2). For optimal results, reaction vessels should be flame dried and purged with argon using anhydrous solvents in all instances.6a If isolable, storage in a dry box or a tightly sealed vessel under an inert atmosphere is recommended. Olah et al.9a describe the phosphate series to be stable under an inert atmosphere at rt without refrigeration. The borate and antimonate series are generally stable for weeks under an inert atmosphere at 0 °C. All dialkoxycarbenium salts are powerful acylating/alkylating agents; therefore skin and eyes should be protected when handling the solutions and especially the isolated salts. Use in a fume hood.

Introduction.

Dialkoxycarbenium salts exhibit an interesting dichotomy in reactivity.2g These ambident electrophiles are powerful acylating and alkylating agents. The mode of reactivity can be altered depending upon the nucleophile, the reagent, the reaction temperature, the reaction time, and the solvent. Prepared in situ, these salts surpass in reactivity other common alkylating agents such as Meerwein's salt, alkyl triflates, and alkyl halides.2,6,8 Each cationic component serves as a versatile electrophile which has proven to be an efficient formylating or alkylating reagent. All of the dialkoxycarbenium salts are accessible by judicious choice of orthoester and Lewis acid. Limitations include solubility and stability, which make the commercially available trialkyloxonium tetrafluoroborates attractive (see Triethyloxonium Tetrafluoroborate, Trimethyloxonium Tetrafluoroborate).7a However, dialkoxycarbenium salts provide a means for efficient acylation or alkylation of weak nucleophiles not accessible from their parent counterparts.

Alkylation of Sulfur Nucleophiles.

Dimethoxycarbenium tetrafluoroborate has been extensively used in the conversion of numerous thiacyclophanes to polycyclic aromatic compounds.3c This method efficiently transforms sulfide linkages into carbon-carbon double bonds via a Stevens rearrangement followed by an elimination step. Using this sequence, dimethyldihydropyrene3c,d was synthesized in five steps, two of which involved the formation of a bis(sulfonium)cyclophane intermediate with dimethoxycarbenium tetrafluoroborate (eq 1).

Formation of other bis(sulfonium) salts using dimethoxycarbenium tetrafluoroborate was successfully applied toward the synthesis of other pyrene derivatives such as [2.2]metaparacyclophene-1,9-diene,3e [7],[7.7]circulene,3f [2.2](2,6)pyridinophene-1,9-diene,3g and [2.2.2](1,3,5)cyclophane-1,9,17-triene.3h Another example of sulfur activation employing both dimethoxycarbenium tetrafluoroborate as well as hexafluorophosphate has been applied to the synthesis of various organic charge-transfer complexes.4a,b Critical for the success of these syntheses is the conversion of various thione derivatives to the corresponding selenone derivatives. Treatment of thieno[3,4-d]-1,3-dithiole-2-thione with dimethoxycarbenium hexafluorophosphate afforded the desired thionium hexafluorophosphate, which was subsequently transformed to the selenone analog in the presence of Hydrogen Selenide (eq 2).

Activation of the carbon-sulfur double bond with dialkoxycarbenium salts has led to the preparative synthesis of similar analogs. Thioimidates can be prepared by the selective alkylation of thioamides using either dimethoxy- or diethoxycarbenium tetrafluoroborate (eq 3).4c,d The products isolated are used as key intermediates in the synthesis of b-lactams. Meerwein's salt also carries out the transformation shown in eq 3. Other examples include the formation of hexachloroantimonate salts via ethylation of dithiolodithione dimers (eq 4).4e Lastly, heterolysis of disulfide bonds has been achieved by treatment of a diaryl disulfide with diethoxycarbenium tetrafluoroborate (eq 5).4f

Alkylation of Nitrogen Nucleophiles.

Dialkoxycarbenium tetrafluoroborates provide an efficient means for the production of secondary amines through nitrilium salt intermediates.5b N-Alkylnitrilium salts other than N-methyl or N-ethyl are not readily accessible using the trialkyloxonium tetrafluoroborates. Treatment of a series of dialkoxycarbenium salts with benzonitrile furnished, after reductive workup, the desired substituted benzylamines (eq 6). Higher analogs such as n-propyl did not provide the desired n-propylbenzylamine but rather isopropylbenzylamine. This rearrangement does limit applications of other higher-order dialkoxycarbenium salts.

Formation of nitrilium salts has also been applied to the field of organometallic chemistry.5c In these examples the reductive workup of the intermediate iminoester with sodium borohydride is eliminated. Diethoxycarbenium tetrafluoroborate is used to perform two nitrogen-based alkylations (eq 7). The resulting complex is isolated and purified by recrystallization.

Another example of activation/reduction is illustrated in the preparation of 1-alkyl-2,1-benzisoxazoline derivatives.5d Treatment of 2,1-benzisoxazoles with dialkoxycarbenium hexachloroantimonate affords the desired 1-alkyl-2,1-benzisoxazolium salts, which are subsequently treated with a variety of nucleophilic reagents (eq 8). The following transformation is catalyzed by in situ preparation of either dimethoxy- or diethoxycarbenium salts as well as the related trialkyloxonium tetrafluoroborates. Nucleophilic reagents employed include Grignards, cyanides, malonates, morpholines, and other amine derivatives. The end products were obtained in good yields without appreciable amounts of ring-opened byproducts.

A final example of nitrogen activation of weak organic bases is in the alkylation of N,N-disubstituted sulfonamides.5e The reagent of choice is dialkoxycarbenium hexachloroantimonate because sulfonamides are inert toward Meerwein's salt. Shown in eq 9 is the formation of two hexachloroantimonates from the corresponding N,N-disubstituted sulfonamides. Subsequent treatment of these salts with aqueous acid effectively cleaves the N-S bond into corresponding amine and sulfonic acid derivatives.

Alkylation of Oxygen Nucleophiles.

Dialkoxycarbenium hexachloroantimonates are versatile reagents in the alkylation of a variety of oxygen-containing substrates.6a Even weak nucleophiles which are inert to trialkyloxonium salts are cleanly and rapidly alkylated. Treatment of diethoxycarbenium hexachloroantimonate with sulfoxides (eq 10),6a aldehydes, ketones, esters (eq 11),6c and amides (eq 12)6a yield alkylated products which can either be isolated as antimonate salts or their subsequent transformation products.

Dimethoxycarbenium tetrafluoroborates are stronger alkylating agents than their parent trialkyloxonium tetrafluoroborates. Interestingly, the preparation of methyl or ethyl Meerwein's salt can be accomplished by treatment of the appropriate dialkoxycarbenium salt with either dimethyl or diethyl ether (eq 13).7 This procedure has been reported to yield the desired trialkyloxonium salt in very high purity.

Aryl-substituted dimethoxycarbenium tetrafluoroborates, although sluggish in reactivity due to the steric conjestion about the carbenium center, will alkylate at oxygen.6b Treatment of 2,6-dimethyl-4-pyrone with an aryl-substituted tetrafluoroborate salt affords the desired 4-methoxy-2,6-dimethylpyrylium tetrafluoroborate in good yield (eq 14).

Acylation of Carbon Nucleophiles.

The foregoing examples illustrate the use of dialkoxycarbenium salts for the selective alkylation of weakly nucleophilic heteroatoms.2g In these examples, reaction conditions of thermodynamic control were generally employed. However, when dialkoxycarbenium salts are used under conditions of kinetic control a different type of product is obtained. Under the latter reaction conditions, carbocyclic or aromatic conjugated cyclic and acyclic ketones are converted into protected derivatives of formyl ketones.8b Employing diethoxycarbenium tetrafluoroborate prepared in situ with a variety of cyclic (eq 15) and acyclic (eq 16) ketones in the presence of Diisopropylethylamine at low temperatures in a methylene chloride solution affords the corresponding b-keto acetals.8c Other functional groups such as halide, nitrile, alkene, arene, and ester functionalities are compatible with this method. Regioselectivity is governed by steric effects; therefore reaction generally takes place at the less substituted a-position.

This method has been extended to the preparation of a,b-unsaturated aldehydes via b-keto acetals (eq 17)8c and some aryl-substituted bicyclo[3.3.1]nonadienones through an acid-catalyzed cyclization of the a-(diethoxymethyl) ketones (eq 18).8d

High levels of regioselectivity are observed when reactions between electron-rich heterocycles and dialkoxycarbenium tetrafluoroborates are carried out. From 2-methylindole, several 3-acylated indoles are produced without N-alkylation (eq 19).8e Conversion to the desired aldehyde or ketone after initial acylation is observed upon aqueous workup.

Treatment of 2,3-substituted indoles with diethoxycarbenium tetrafluoroborates results in selective acylation on the nitrogen.8f Interestingly, however, upon switching to the dimethoxy derivative, alkylation on nitrogen predominates even in the 2-methylindole series. As the steric size of the carbenium ion increases, for example when switching from dialkoxycarbenium salts to dialkoxyalkylcarbenium salts, one observes a shift from acylation to alkylation as well as a decrease in overall reactivity.

Another interesting variation in the electrophilic reactivity of these ambident reagents exists in the area of anionic acylations. Treatment of dimethoxycarbenium tetrafluoroborate, predominately an alkylating agent, with either lithium cyclononatetraenide8g or potassium cyclopentadienylirondicarbonyl8h results in the formation of the desired acylated derivatives.

Related Reagents.

Dimethyliodonium Hexafluoroantimonate; O-Methyldibenzofuranium Tetrafluoroborate; Triethyl Orthoformate; Triethyloxonium Tetrafluoroborate; Trimethyloxonium Tetrafluoroborate.


1. (a) Pindur, U.; Müller, J.; Flo, C.; Witzel, H. CSR 1987, 16, 75. (b) Perst, H. Oxonium Ions in Organic Chemistry; Verlag Chemie: Weinheim, 1971; pp 145-149.
2. (a) Meerwein, H. MOC 1963, 6/3, 325. (b) Fieser, L. F.; Fieser, M. FF 1971, 5, 714. (c) Fieser, L. F.; Fieser, M. FF 1971, 5, 716. (d) Meerwein, H.; Hederich, V.; Morschel, H.; Wunderlich, K. LA 1960, 635, 1. (e) Meerwein, H.; Bodenbenner, K.; Borner, P.; Kunert, F.; Wunderlich, K. LA 1960, 632, 38. (f) Meerwein, H.; Borner, P.; Fuchs, O.; Sasse, H. J.; Schrodt, H.; Spille, J. CB 1956, 89, 2060. (g) Hünig, S. AG(E) 1964, 3, 548.
3. (a) Fieser, L. F.; Fieser, M. FF 1970, 4, 114. (b) Fieser, L. F.; Fieser, M. FF 1971, 5, 623. (c) Mitchell, R. H. H 1978, 11, 563. (d) Mitchell, R. H.; Boekelheide, V. TL 1970, 1197. (e) Boekelheide, V.; Anderson, P. H. TL 1970, 1207. (f) Yamamoto, K. PAC 1993, 65, 157. (g) Boekelheide, V.; Lawson, J. A. CC 1970, 1558. (h) Boekelheide, V.; Hollins, R. A. JACS 1970, 92, 3512.
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7. (a) Curphey, T. J. OS 1971, 51, 142. (b) Earle, M. J.; Fairhurst, R. A.; Giles, R. G.; Heaney, H. SL 1991, 728. (c) Silverman, R. B.; Olofson, R. A. CC 1968, 1313.
8. (a) Fieser, L. F.; Fieser, M. FF 1977, 11, 175. (b) Mock, W. L.; Tsou, H.-R. JOC 1981, 46, 2557. (c) Gupta, R. D.; Ranu, B. C.; Ghatak, U. R. IJC(B) 1983, 22B, 619. (d) Dasgupka, R.; Ghatak, U. R. TL 1985, 26, 1581. (e) Pindur, U.; Flo, C. M 1986, 117, 375. (f) Flo, C.; Pindur, U. LA 1987, 509. (g) Sabbioni, G.; Neuenschwander, M. HCA 1985, 68, 623. (h) Theys, R. D.; Hossain, M. M. TL 1992, 33, 3447.
9. (a) Olah, G. A.; Olah, J. A.; Svoboda, J. J. S 1973, 490. (b) Dusseau, Ch. H. V.; Schaafsma, S. E.; Steinberg, H.; de Boer, Th. J. TL 1969, 467. (c) Ramsey, B. G.; Taft, R. W. JACS 1966, 88, 3058.
10. Pindur, U.; Flo, C. SC 1989, 19, 2307.

David C. Forbes

University of Illinois, Urbana-Champaign, IL, USA



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