Trialkyloxonium fluoroborates

N-Alkylations, especially of oxo-di- and tetra-hydro derivatives, e.g. (28)->(29), have been carried out readily using a variety of reagents such as (usual) alkyl halide/alkali, alkyl sulfate/alkali, alkyl halide, tosylate or sulfate/NaH, trialkyloxonium fluoroborate and other Meerwein-type reagents, alcohols/DCCI, diazoalkanes, alkyl carbonates, oxalates or malon-ates, oxosulfonium ylides, DMF dimethyl acetal, and triethyl orthoformate/AcjO. Also used have been alkyl halide/lithium diisopropylamide and in one case benzyl chloride on the thallium derivative. In neutral conditions 8-alkylation is observed and preparation of some 8-nucleosides has also been reported (78JOC828, 77JOC997, 72JOC3975, 72JOC3980). 

The quaternization of 1-substituted imidazoles is usually easy unless steric factors intervene, or strongly electron-attracting groups are present, for example, 1-acylimidazoles can only be alkylated at N(3) with powerful alkylating agents such as methyl fluorosulfonate or trialkyloxonium fluoroborates. Trimethyloxonium fluoroborate does not methylate 1-dimethylaminosulfonylimidazole. Regiospecific synthesis of 3-substituted L-histidines can be achieved by alkylation of Ar-/-butoxycarbonyl-l-phenacyl-L-histidinc methyl ester at N(3), followed by reductive removal of the phenacyl group (Scheme 15). 

No comparison between trialkyloxonium fluoroborates and dialkyl sulfates has been made, but analysis of available data shows that oxonium salts are more generally applicable reagents for the preparation of lactim ethers. The alkylation of 3-carbethoxypiperid-2-one (7)25 and morpholin-3-one (8)32 with dimethyl sulfate failed, but with triethyloxonium fluoroborate these compounds gave 2-ethoxy-3-carbethoxy-3,4,5,6-tetrahydropyridine (9) and 3-ethoxy-3,4-dehydro-morpholine (10) in excellent yield. The selective character of triethyloxonium fluoroborate is shown in its reaction with 3,3-diethyl-5-methylpiperidine-2,4-dione (11 ).25 Reaction of 11 with the calculated quantity of dimethyl sulfate resulted in alkylation of the carbonyl group in position 4 with formation of 12, but reaction of 11 with triethyloxonium fluoroborate gave the lactim ether (13). 

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. 

Borch prepared these reagents in about 85% yield by the reaction of orthoformate esters with boron trifluoride etherate in methylene chloride at —30° (3, 303). They are low-melting crystalline solids. Borch reported that these reagents are even more potent alkylating reagents than trialkyloxonium fluoroborates. 

TV-Acyl derivatives of heterocycles can often be quaternized by hard alkylating agents, such as trialkyloxonium fluoroborates ° or methyl fluorosulfonate. The quaternary salt is not usually isolated, but N-alkylated derivatives are obtained whose structures are generally different from those obtained by alkylation of anions (Sections IV,C,2). This method, due to Olofson and Kendall, has been used with success in azapentalenes [Eqs. (34) and (35)1, where the products 384 and 385 are different from those obtained by alkylation of the anions 361 and 364, respectively (Scheme 16). 

No alkoxy-l,3-dithiolium salts (250) are formed by the action of alkyl halides, dimethyl sulfate, or trialkyloxonium fluoroborates on isodithiones, which, like the Baumann-Fromm disulfides (Section II, A, 2,c), are stable towards these reagents. ... 

Trialkyloxonium fluoroborates can be conveniently prepared from the ether, alkyl halide, and silver fluoroborate. 

Trialkyloxonium fluoroborate/triethylamine Synthesis of enamines from carboxylic acid amides... 

Trialkyloxonium fluoroborate Iminoesters from carboxylic acid amides CONH -> C( N )OR... 

Trialkyloxonium fluoroborates Alcohols in the presence of an acid catalyst 2.14 2.15.1 Exocyclic O-alkylation in mesoionic ring systems [92] Catechol and related substances N-Acyl derivatives, when these groups are to be preserved N-Deacylation ocairs [93, 94] Two electron donating functions in the aromatic ring are essential for the alkylation to occur possible risk of racemization of optically active substances... 

A solution of the substrate in an inert solvent (such as dichloromethane) is treated with an equimolar amount of trialkyloxonium fluoroborate, at a suitable temperature and with the exclusion of moisture. After concentration, the product often crystallizes in the form of a fluoroborate salt, which can be decomposed with a solution of sodium bicarbonate. Alternatively, when they ect other functions present, alkoxides in be used. For the conversion of liquid substances, solid trialkyloxonium fluoroborate is added, and the mixture is stirred until the reagent dissolves. Warming to a suitable temperature may be necessary at this step. 

Nitro compounds, ar. Nitrobenzene N-Nitramines Oxonium fluoroborate Trialkyloxonium salt Trialkyloxonium fluoroborate Carboxylic acid esters Isopropenyl acetate Chloroformic acid esters Ethyl chloroformate Methyl trichloroacetate... 

Sodium hydride trialkyloxonium fluoroborate N-Alkylation of sulfoximines... 

Sodium tetrahydridoborate trialkyloxonium fluoroborate Cyclic imines from lactams... 

Trialkyloxonium fluoroborate Alkoxylcyclimmonium salts from cyclic N-oxides... 

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