Triethyloxonium fluoroborate

Substituted 1,2,3,4-thiatriazoles (93) are alkylated only under very forcing conditions with triethyloxonium fluoroborate, but then give the expected products (94) (75JOC431). 

Triethyloxonium fluoroborate [368-39-8] M 190.0, m 92-93°(dec). Crystd from diethyl ether. Very hygroscopic, and should be handled in a dry box and stored at 0°. [Org Synth 46 113 1966.] Pure material should give a clear and colourless soln in dichloromethane (1 in 50, w/v). 

The reaction between phthalimidine (30) and triethyloxonium fluoroborate is reported to give the fluoroborate salt of 1-ethoxyiso-indolenine, from which the free base (35) can be liberated.The iso-indolenine (35) apparentlj shows no detectable tautomerism with the isoindole form (see Section IV, A). 

Alkylation of compound 2 has been confirmed at position 1 as predicted for methylation (dimethyl sulfate) and ethylation (triethyloxonium fluoroborate) (93T4307), and in the simple case of compound 193 (94AJC1009), and in the compound 194 (82MI1). The ylide 195 (84JCS(P1)1891) is substituted at position 3. 

Russian workers have shown that alkylation of the P" derivatives (13) with triethyloxonium fluoroborate takes place at phosphorus rather than... 

Piperazine-2,5-diones react with trimethyloxonium fluoroborate (Meer-wein s reagent) or triethyloxonium fluoroborate to generate the corresponding lactim ethers. 

The earliest report on such lactim ether formation was from Sammes [72JCS(P1)2494], who converted piperazine-2,5-dione to 2,5-diethoxy-3,6-dihydropyrazine (173) with an excess of triethyloxonium fluoroborate. Subsequently, Rajappa and Advani (73T1299) converted proline-based piperazine-2,5-diones into the corresponding monolactim ethers. The starting material was a piperazinedione in which one of the amino acid units was the secondary amino acid proline, and the other a primary amino acid. This naturally led to the regiospecific formation of a monolactim ether (169) (on O-alkylation) from the secondary amide, whereas the tertiary amide remained intact. This was later extended to piperazine-2,5-diones in which the secondary amino acid was sarcosine [74JCS(P 1)2122], leading to the monolactim ethers (170). 

There has been little systematic study of the chemistry of 1,4-oxazepines. Vigorous acid hydrolysis cleaves the amide linkage in (369 R1=Ph, R2 = H) and recyclization gives 2-o-hydroxyphenyl-5-phenyloxazoline and l,2,3,4-tetrahydro-l,8-dihydroxy-3-phenyl-isoquinoline. The l,4-benzoxazepin-5-one (353) can be alkylated at N but on treatment with triethyloxonium fluoroborate it is converted to 5-ethoxy-3-phenyl-l,4-benzoxazepine — one of the very few examples of a fully unsaturated 1,4-oxazepine ring. This product is isomerized to l-ethoxy-4-hydroxy-3-phenylisoquinoline when boiled in methanol. The 4,l-benzoxazepine-2,5-diones (348) are converted to quinazolines by reaction with ammonia. The dihydro-l,4-oxazepin-5-one (343) can be acetylated at nitrogen and bromi-nated at the 6-position. 

The polymerization of (355) in the presence of triethyloxonium fluoroborate in 1,2-dichloroethane proceeds to give a product with a degree of polymerization of about 30 at all conversion percentages. This arises because of the slow initiation step and the presence of chain breaking reactions with this catalyst (60MI51900). 

Activated alkynes have been shown to react in a Diels-Alder style with phthalans to furnish polysubstituted naphthalenes (80CJC2573). 1,1-Diethoxyphthalan (41) was prepared by alkylation of phthalide (40) with triethyloxonium fluoroborate, followed by treatment... 

Triethyloxonium fluoroborate can be prepared from 1-chloromethyloxacyclo-propane and a BF3-etherate according to the equation... 

Among the important reagents for which preparative procedures are given are 2,2 -bipyridine (by nickel directed and catalyzed dehydrogenation of pyridine p. 5), formamidine acetate (p. 39), phenyltrichloromethylmercury (p. 98), and trimethyl- and triethyloxonium fluoroborate (pp. 120, 113). The preparation of palladium catalyst ( Lindlar ) for the selective reduction of acetylenes is described (p. 89), as is the use of di-phenyliodonium-2-carboxylate, as a precursor of benzyne in the synthesis of 1,2,3,4-tetraphenylnaphthalene (p. 107). 

The same authors studied the stereochemistry of alkylation of 4-t-butyl-cyclohexanone. Alkylation of enolate ion 467 with triethyloxonium fluorobor-ate yielded a mixture of 0-alkyl product and approximately equal amounts of... 

Pyrazines form diquaternary salts on treatment with triethyloxonium fluoroborate. Using this reagent the 1,4-diethylpyrazinium difluoro-borates of pyrazine, 2,5-dimethyl-, and 2,6-dimethylpyrazines have been obtained in 96, 97, and 46% yield, respectively. The reaction is subject to considerable steric hindrance since the yield of diquaternary salt from tetramethylpyrazine is only 6%. The diquaternary salts are extremely reactive substances and that of the parent compound is shown by ESR measurements to be readily reducible to the radical cation [Eq. (7)].150... 

The irans-benzylidene derivative (188), obtained as the major product of condensation of 3-methylpiperazine 2,5-dione and benzaldehyde in the presence of acetic anhydride, undergoes photoisomerization to the cis isomer (191) on irradiation in methanol. Both isomers have been converted into tetrahydropyrazine imino ethers (189) and (192) by treatment with triethyloxonium fluoroborate. The trans compound reacts more slowly and gives a lower yield of imino ether and this is attributed to steric hindrance. Compounds 188 and 191 are de-acetylated on treatment with methanolic 2 N potassium hydroxide. The trans and cis isomers (187) and (190), so produced are converted into 3-benzyl-2,5-dihydroxy-6-methylpyrazine (144) when heated at 100° with sodium hydroxide.384 Treatment of the dichloroacetyl derivative of phenylalanine with methylamine gives l-methyl-3-benzylidenepiperazine 2,5-dione with the stereochemistry shown.384a... 

Oxazoles and benzoxazoles yield salts with acids, alkyl halides, methyl toluene-p-sulfonate, triethyloxonium fluoroborate, etc. Quaternization is subject to the well-known steric effect of bulky substituents 2-phenylbenzoxazole, for instance, does not react with ethyl iodide even at 240 °C. The weakly basic nature of oxazole (see Section 4.18.2.4) is reflected in the instability of its simple salts, such as hydrochlorides and picrates, which are readily hydrolyzed, even in air. 2-Aminooxazoles and 2-aminobenzoxazoles are alkylated at the ring nitrogen atom the anilinonaphthooxazole (124), on the other hand, reacts with methyl iodide to yield a mixture of methyl derivatives (equation 1). 

Alkylation of 8-(un)substituted-10,10,10a-trimethyl-1,2,3,4,10-1 Oa-hexahydro-pyrimido[l,2-a]indol-2-ones (46) gave (unlike the five-membered ring case) chiefly the O-ethers (47), and gave them exclusively when triethyloxonium fluoroborate was the alkylating agent. Upon treatment with acid, these similarly gave the 1-alkoxy-carbonylethyl-2-methylene-3,3-dimethyl-5-substituted indolines (45, n = 2).50... 

The direct alkylation methods include the reaction of lactams with diazomethane14 and the alkylation of metal salts of lactams with alkyl halides.15 These two methods are not often used nowadays, because the alkylation can more conveniently be carried out with dialkyl sulfates or triethyloxonium fluoroborate. 

In recent years the alkylation of lactams has been achieved using tertiary oxonium salts, particularly triethyloxonium fluoroborate.19,20 This reaction proceeds via cation formation (cf. 5). Treatment of the salt with base leads to the lactim ether. 

The high tendency to O-alkylation by triethyloxonium fluoroborate compared with other alkylating agents is observed also in the alkylation of keto-enols,28 the ambident ions of nitroparaffins,29,30 and potassium diethylthiophosphate.31... 

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). 

Rather surprisingly 2,4,6-triphenyl-4/f-thiopyran (74) is oxidized to the corresponding thiopyrylium 9 by alkylating agents, such as methyl iodide, dimethyl sulfate, and triethyloxonium fluoroborate (62JA2090). 

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