Trimethyloxonium tetrafluoroborate alkylation with

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... 

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. 

Very few examples of electrophilic attack at sulfur(II) have been reported for these systems, with the exception of oxidation. Alkylation of the benzothiadiazine (88) with trimethyloxonium tetrafluoroborate gave a poor yield of the imino ether (89). The major product (90) resulted from alkylation at sulfur followed by hydrolytic ring opening of the resulting azasulfonium salt (79JCR(S)214). 

The 2-substituted tetrazole 1-oxides 550 were prepared from the corresponding hydroxytetrazoles 549 by methylation with trimethyloxonium tetrafluoroborate in CH2C12 at 20°C (1984BAU142) or by benzoylation of 1-hydroxytetrazole 549 (1913G71) (Scheme 165). Since N-alkylation and... 

Base-sensitive substrates require some special precautions With the very potent alkylating agent methyl triflate, the highly hindered (and expensive) base 2,6-di-fert-butylpyridine can be used as shown in Scheme 4.114 22 205 Alternatively O-methylation using a combination of trimethyloxonium tetrafluoroborate and l,8-bis(dimethylamino)naphthalene in dichloromethane can be used although this is also a very expensive method [Scheme 4 115].206 Evans and co-workers have made a systematic study of the best conditions for 0-methylating hindered multifunctional substrates,207... 

Hi0 chromium carbene may be prepared by addition of a vinyllithiurn to chromtum hexacarbonyi followed by alkylation with a reactive electrophile such as trimethyloxonium tetrafluoroborate (Meerwein s salt. Me..O BF,-. ... 

Alkyl cyclopropyl ethers, e.g. 5, have been prepared by treating the corresponding acetates with an alkyllithium (methyl- or butyllithium) and then with a methylating agent like ioodome-thane or trimethyloxonium tetrafluoroborate. ... 

Methylation of iminothiazolines (175) followed by reaction with NaHSe gives 2-selenoxo-thiazolines (176) (Equation (27)) <84PJC447>. 3-Alkyl-2-(A-cyanoimino)thiazolidines (177) are methylated with trimethyloxonium tetrafluoroborate the resulting nitrilium salts react with sodium diethyl malonate to afford methylenethiazolidines (178) and urea derivatives (179) along with the iminothiazolidines (180) (Equation (28)) <93H(36)55>. 

The proposal of Lee and Wu was criticized by 01 ah et al [21] who were unable to induce the insertion of singlet methylene (generated by CH2N2 photolysis) into trimethyloxonium tetrafluoroborate. The alkylation of CH2N2 by alkyl cations or their precursors, on the other hand, is known. Accordingly, Olah and co-workers proposed an alternate interpretation where a labilized "incipient methyl cation" on the acid site reacted with CH2M2 to form ethylene. 

Dimethoxy-3,6-dihydropyrazine (109), prepared by methylation of 2,5-piperazinedione with trimethyloxonium tetrafluoroborate, is susceptible to lithiation because the protons at C-3 and C-6 are activated by adjacent imine moieties. The lithium salt of this bislactim ether reacts with the 2-chloro-l-phenylsulfonyl alkene (110) to give the 3-substituted pyrazine (111) (Scheme 25) <89JCS(P1)453>. The bislactim ether from piperazinedione cyclo(L-Val—Gly) is lithiated with butyl-lithium and then treated with ketones, alkyl halides, or others to form, nearly stereospecifically, ran5-3-isopropyl-6-substituted piperazinediones due to the steric influence of the isopropyl group <828866, 838673). Similar stereoselective syntheses have been achieved in reactions starting from cyclo(L-Val—D,L-Ala) <828864, 918939). Acid hydrolysis of these products affords chiral a-amino acids. 

The salt is prepared in 62% yield by alkylation of di-r-butylcarbodiimide with trimethyloxonium tetrafluoroborate. ... 

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