Trialkyloxonium salts alkylation with

Meerwein s reagent, triethvloxonium tetrafluoroborate, is a powerful ethylating agent that converts alcohols into ethyl ethers at neutral pH. Show the reaction of Meerwein s Teagent with cyclohexanol, and account for the fact that trialkyloxonium salts are much more reactive alkylating agents than alkyl iodides. 

Other examples of esterification with trialkyloxonium salts have been reported.7,8 The present procedure offers the advantages that the reactive carboxylate ion is generated in sitv and that a low-boiling, nonaqueous solvent is employed, whereby the experimental procedure is considerably simplified. A related method has been reported which utilizes a hindered amine wdth dimethyl sulfate [Sulfuric acid, dimethyl csterj as the alkylating agent.9 The present procedure is carried out under somewhat milder conditions and avoids the use of highly toxic reagents. 

Tosylhydrazones, with methyllithium to give olefins, 51, 69 Trialkyloxonium salts, as alkylating agents, 51,144... 

A-Alkoxypyridinium salts and their benzo analogues can be formed by treatment of the iV-oxides with alkyl halides, dialkyl sulfates (e.g. Scheme 111) <730SC(5)269), alkyl arenesul-fonates, trialkyloxonium salts (66CB1769), and trialkyl phosphites and their thio analogues (71JGU524). 

Several 1-alkoxyisoindoles have been prepared by alkylation of phthalimidines with trialkyloxonium salts (73TL19H). 

In many cases, the main step in the syntheses of trialkyloxonium salts is the alkylation of a dialkyl ether with a reactive intermediate oxonium ion formed in situ. Thus, the most widely used method for preparing trialkyloxonium tetrafluoroborates by the reaction of epichlorohydrin and BF3 is based on the intermediacy of the inner oxonium salt 3291 95 97 [Eq. (4.19)]. 

HSAB is particularly useful for assessing the reactivity of ambident nucleophiles or electrophiles, and numerous examples of chemoselective reactions given throughout this book can be explained with the HSAB principle. Hard electrophiles, for example alkyl triflates, alkyl sulfates, trialkyloxonium salts, electron-poor car-benes, or the intermediate alkoxyphosphonium salts formed from alcohols during the Mitsunobu reaction, tend to alkylate ambident nucleophiles at the hardest atom. Amides, enolates, or phenolates, for example, will often be alkylated at oxygen by hard electrophiles whereas softer electrophiles, such as alkyl iodides or electron-poor alkenes, will preferentially attack amides at nitrogen and enolates at carbon. 

Lactams and some non-cyclic, secondary amides (RCONHR) can be alkylated with high regioselectivity either at nitrogen (Section 6.6) or at oxygen. N-Alkylations are generally conducted under basic reaction conditions whereas O-alkylations are often performed with trialkyloxonium salts, dialkyl sulfates, or alkyl halides/silver salts without addition of bases. Protonated imino ethers are formed these are usually not isolated but are converted into the free imino ethers with aqueous base during the work-up. Scheme 1.8 shows examples of the selective alkylation of lactams and of the formation of 2-pyrrolidinones or 2-iminotetrahydrofurans by cycli-zation of 4-bromobutyramides. 

Trialkyloxonium fluoroborates give better yields of lactim ethers than other alkylating agents because of the selectivity of these reagents in the O-alkylation of lactams. This was borne out by Meerwein at al.,42 who arranged carbonyl compounds according to their capacity to undergo alkylation with oxonium salts as follows lactams > acyclic amides > lactones > carboxylic esters > ketones > aldehydes. 

Trialkyloxonium salts with the more stable PFg or SbFg anions can be prepared, according to Olah, by using orthoformates as the alkylating agents ) ... 

The alkylation of aromatic 1,2,4-triazines has been studied by various groups.251 -259 Alkylation with iodomethane affords the red 1-methyl-1,2,4-triazinium salts 4c-j predominantly and in a few cases yields the colorless 2-methyl-l,2,4-triazinium salts 5. The best results are obtained when nitromethane is used as the solvent for the alkylation. Similar results are obtained when trialkyloxonium tetrafluoroborates or dialkyl sulfates are used as alkylation agents. The formation of either the 1- or the 2-isomers depends on the substituents bound to the 1,2,4-triazine ring. In cases with a bulky substituent in the 3-position, alkylation occurs exclusively at Nl, in other cases mixtures of N1 and N2 alkylated triazinium salts are obtained. Introduction of a more bulky substituent, such as isopropyl or aryl substituents, in the 6-posi-tion hinders quaternization at Nl. 

Alkylation with methyl iodide or trialkyloxonium fluoborate occurs with some difficulty by analogy with 5-amino-l,2,4-thiadiazoles,74 the products are formulated as N4 quaternary salts. The 5-methyl group (in 392) readily undergoes condensation with aromatic aldehydes to 5-styrylthiadiazoles (393). The action of carboxylic acid esters gives ethoxalyl derivatives (394) and that of isoamyl nitrite produces the oxime (395).287... 

The reactions of the phosphabenzene system [124] confirm these conclusions. Phosphabenzenes have low basicity towards hard acids. They are not protonated by CF3CO2H nor alkylated by trialkyloxonium salts. However, soft acids attack at phosphorus. For instance, 2,4,6-triphenyl-phosphabenzene forms compounds 4 with the hexacarbonyl derivatives of Cr, W and Mo in which the phosphorus coordinates to the metal, possibly with metal-P back-donation. The complexes 4 rearrange photochemically or thermally affording the 67i-heteroarene complexes 5. Although 2,4,6-triphenyl-pyridine is protonated on nitrogen, it undergoes complex formation with chromium hexacarbonyl exclusively on the phenyl moieties yielding the ri -arene complexes 6 [125]. 

Useful methods for specific 2-0 or 4-0 methylations (or ethylations) of tetronic acids have been published (Scheme 20). °" The more reactive -oxygen can be alkylated by treatment with dialkyl sulphates under a variety of conditions whereas preparation of the 2-O-alkyl derivative requires prior acylation of the 4-oxygen, followed by alkylation using trialkyloxonium salts (see ref. 148). Some very interesting chemistry has been evolved during efforts towards a total... 

Potent alkylation reagents like trialkyloxonium salts effect alkylation of 2H-pyran-2-ones at the C=0 group and yield 2-alkoxypyrylium salts, for example, 23 with [Me30]Bp4 ... 

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