Triethyloxonium tetrafluoroborates alkylation with

Arylmethyl(homobenzyl)ethylsulfonium salts are appropriate substrates for Suzuki-type coupling reactions. In this reaction, performed on a polymer-bound sulfonium tetrafluoroborate, the benzyl fragment on the sulfur atom was transferred to the boronic acid residue. The sulfonium salt was prepared from an al-kylthiol resin by alkylation with a substituted benzyl halide to give thioether 98 and subsequent alkylation with triethyloxonium tetrafluoroborate. Reaction with a boronic acid derivative yielded diaryl methanes 99 [94] (Scheme 6.1.22). 

It is very interesting, however, that in alkane potassium diazoate alkylations with Meerwein s reagent (triethyloxonium tetrafluoroborate, Et30+BF4) in CH2C12 suspensions or with alkyl halides in hexamethylphosphoric triamide solutions, azoxy compounds (6.4) are formed, i.e., alkylation takes place at the (3-nitrogen (Moss et al., 1972). 

Neutral tertiary and secondary amides react with very reactive alkylating agents, such as triethyloxonium tetrafluoroborate, to give O-alkylation.63 The same reaction occurs, but more slowly, with tosylates and dimethyl sulfate. Neutralization of the resulting salt provides iminoethers. 

Some alkylations of ring nitrogen atoms are shown in Scheme 5. Study on alkylation of the [l,2,4]triazolo[5,l-cHl /lltriazine derivative 41 have been carried out by Chupakhin and co-workers <2002IZV1594>. The best result was obtained with triethyloxonium tetrafluoroborate as a reagent. The ethylation was found to proceed selectively on N-4 atom in the six-membered ring to result in formation of the quaternary salt 42. 

In the course of studies on the synthesis of [l,2,4]triazolo[3,4-A][l,2,4,5]tetrazines, Kotschy et al. investigated the alkylation of the morpholino derivative 13 of this ring system <2000ARK259>. It has been found that ethylation carried out with triethyloxonium tetrafluoroborate took place exclusively on the five-membered ring and yielded a mixture of 1-ethyl 14 and 2-ethyl 15 quaternary salts. 

One of the major advantages of oxonium salts is that alkylations can be effected under reaction conditions that are generally much milder than those necessary with the more conventional alkyl halides or sulfonates. Triethyloxonium tetrafluoroborate, for example, has usually been employed at room temperature in dichloromethane or dichloroethane solution. Occasionally chloroform16-22 or no solvent at all4-20 is used. Difficult alkylations can be effected in refluxing dichloroethane.29 30 The less soluble trimethyloxonium tetrafluoroborate has been used as a suspension in dichloromethane or dichloroethane, or as a solution in nitromethane or liquid sulfur dioxide. Reports of alkylations in water23 and trifluoroacetic acid21 have also appeared. Direct fusion with trimethyloxonium tetrafluoroborate has succeeded in cases where other conditions have failed.25-30... 

Anhydro-5-hydroxy-l,2,3,4-oxatriazolium hydroxides (4) are alkylated by triethyloxonium tetra-fluoroborate to give 5-ethoxy-1,2,3,4-triazohum tetrafluoroborates (35 Y = O) <88MRC1012, 91BAP265). Anhydro-5-thiolo-l,2,3,4-oxatriazolium hydroxides (5) are likewise alkylated with triethyloxonium tetrafluoroborate, but not with methyl iodide, producing the ethylthio derivatives... 

Treatment of meso-ionic l,2,3,4-oxatriazole-5-thiones (286) (Section VII, I, 3) with boiling ethanoUc ammonia yields the isomers 297. These belong to a new class of meso-ionic heterocycle, which by O-alkylation with triethyloxonium tetrafluoroborate 3rield the salts 298, These are useful intermediates for the sjmthesis of a number of novel types of meso-ionic 1,2,3,4-thiatriazoles (299, 300, and 301). The l,2,3,4-thiatriazol-5-ones (297) have dipole moments in accord with their meso-ionic formulation. They are remarkably stable to acidic hydrolysis, and 1,3-dipolar cycloaddition reactions have not been observed alkaline hydrolysis yields aryl azides. 

The unsymmetrical 3,6-dialkoxy-2,5-dihydropyrazines are prepared via the jV-carboxyanhy-drides of the particular amino acid (e.g., 7) and subsequent reaction with the methyl ester of glycine or alanine to give the corresponding cyclodipeptides (e.g., 8). These hexahydrodioxopy-razines are converted to the 2,5-dialkoxy-3,6-dihydropyrazines by alkylation using Meerwein salts, such as trimethyloxonium tetrafluoroborate or triethyloxonium tetrafluoroborate n lb. 

O -Alkylations of azepin-2-ones, and benzazepin-2-ones, are most efficiently brought about by trialkyloxonium tetrafluoroborates (Meerwein s reagents) (B-69MI51600,73JOC1090, 81HCA373). S-Alkylation of the thiones is effected similarly. These oxonium salts have also proved useful for the alkylation of azepinedione precursors of azatropones and azatropolones (72JOC208) (see also Section 5.16.3.1.2). 5//-Dibenz[f>,e]azepine-6,11 -dione with triethyloxonium tetrafluoroborate O-ethylates at the amide carbonyl and not at the ketonic carbonyl as was first proposed (72AJC2421). 

In the course of O-alkylation with triethyloxonium tetrafluoroborate, the lactim ethers of 1,4-dihydro-3(2//)-isoquinoIinones were obtained (75JMC395). These are useful starting materials for reactions with amines resulting in 1,4-dihydro-3-isoquinolylamines (85EUP139296). By means of bifunctional amines, further condensed hetero-ring compounds could be synthesized (73JMC633). 

Oxadiazoles are difficult to alkylate. However, N-methylfurazinium salts are formed on heating furazans with dimethyl sulfate (74AJC1917,95JCS(P1)1083) the reaction is approximately 7 and 62 times slower, respectively, than the corresponding methylations of 1,2,5-thiadiazole and isoxazole. The N-ethyl salts of furazan itself and 3-phenylfurazan have been prepared using triethyloxonium tetrafluoroborate (64JA1863). 

Whereas the reaction of the linearly fused 117/-pyrido[2,l -h]quina-zolin-ll-one (27) with alkylating agents (dimethyl sulfate at 120°C, and tri-ethyloxonium tetrafluoroborate in methylene chloride at 20°C) gave exclusively 7V(5)-alkylated quaternary salts (107), that of the isomeric angularly fused 6//-pyrido[l,2-a]quinazolin-6-one (28) with the soft methyl iodide afforded only the iV(5)-methyl quaternary iodide (108, X = I). The reactions of 28 with the hard dimethyl sulfate and triethyloxonium tetrafluoroborate yielded a mixture of 5-methyl-6-oxo-6//-pyrido[l,2-a]quinazolinium salts (108) and 6-alkoxypyrido[l,2-a]quinazolinium salts (109) (90JHC2005). 

The base-catalyzed alkylation of oxindoles favors C-alkylation, and O-alkylation is observed with halides only for particularly favorable intramolecular alkylations (B-70MI30614). Triethyloxonium tetrafluoroborate, on the other hand, gives the O-alkylated... 

Alkylation of 3-aryl-l,2,3,4-thiatriazolium-5-olates 38 with triethyloxonium tetrafluoroborate leads to 5-ethoxy substituted thiatriazolium salts 37 (R = Ar) <1975T1783>. In the same manner, the aminides 129 react with iodo-methane to afford the thiatriazolium salts 131 with disubstitution at the exocyclic nitrogen (Scheme 31) <1998JMT27>. Also the mesoionic compounds 127 are readily alkylated with different alkylating agents <1997MRC124>. 

Resin-bound benzylic thioethers can be converted to sulfonium salts by S-alkylation with triethyloxonium tetrafluoroborate. These sulfonium salts react with palladium(O) complexes to yield benzylpalladium complexes, which undergo Suzuki coupling with arylboronic acids (Entry 7, Table 4). 

Alkylation of mesoionic 3-aryl-1,2,3,4-thiatriazol-5-ones (79 X = S, Y = 0, R = Ph, 4-MeC6H4, 4-ClC6H4) and of mesoionic 3-phenyl-l,2,3,4-oxatriazole-5-thione (79 X = 0, Y = S, R = Ph) with triethyloxonium tetrafluoroborate yields thiatriazolium salts (80 equation 51) <79JCS(Pl)732). 

Alkylation with triethyloxonium tetrafluoroborate of a 1,2,3,4-thiatriazole substituted in the 5-position with an aryl or an alkylthio group gives a thiatriazolium salt (81 equation 52) (76AHC(20)145). With an alkyl- or aryl-amino group in the 5-position, however, a 4,5-disubstituted thiatriazoline is formed (see Section 4.28.2.5.2). Under similar alkylation conditions 5-ethoxythiatriazoles decompose completely to nitrogen, sulfur and ethyl cyanate. This is the normal thermal decomposition reaction of 5-alkoxythiatriazoles (see Section 4.28.2.3.l(i)) <76AHC(20)145). 

Mesoionic l,2,3,4-oxatriazole-5-thiones (86) and thiatriazol-5-ones (88) are alkylated with triethyloxonium tetrafluoroborate to give 3,5-disubstituted oxa- and thia-triazolium tetrafluoroborates (80 equation 51), while oxatriazolethiones (86) were found to be inert towards methyl iodide (76CC306,79JCS(Pl)732>. 

The 1,3 -dithiolane ring also can be cleaved by alkylative hydrolysis using different reagents (77S357). For example treatment of the 1,3-dithiolane derivative (220) with triethyloxonium tetrafluoroborate followed by hydrolysis with copper(II) sulfate solution and basification gives the ketone (221) in 95% yield (77S357). 

Hydrolysis of 2-alkyl-l,3-dithanes A recent method for this reaction involves oxidation with periodate to the monosulfoxide followed by alkylation with triethyloxonium tetrafluoroborate to form a l-ethoxy-l,3-dithianium tetrafluoroborate. Salts of this type are hydrolyzed by water at 5°. 

Alkylation of several thietane 1-oxides has been accomplished by treatment of the sulfoxide with trimethyl- or triethyloxonium tetrafluoroborate/ or hexa-chloroantimonate or with methyl iodide-silver tetrafluoroborate. Non-nucleophilic anions are preferred to avoid ring opening. 

The sulfur atom of naphthothiete 205 may be methylated with trimethyl-oxonium tetrafluoroborate to give the stable salt. 3-Phenylthiete 213 may be alkylated with trimethyl- or triethyloxonium tetrafluoroborate or the trifluoro-methanesulfonate esters The salts are unstable. Alkylation of 218b with methyl iodide gives a ring-opened product, the reaction being facilitated by electron donation from the iron atom. ... 

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