Alkyl nitronate salts

Table III. Nitration of Alkyl Nitronate Salts with Nitronium Tetrafluoroborate...

Diazo compounds and oxonium salts are the most efficient alkylating agents in the synthesis of alkyl nitronates. It is assumed that diazo compounds are inserted into the O-H bond in the aci forms of the corresponding AN, whereas oxonium salts generally react with AN anions. 

In reactions of certain alkyl halides with salts of polynitromethanes, C-alkyla-tion can also be diminished and target O-nitronates can be prepared in satisfactory yields (21, 22) (Scheme 3.8, Eq. 2). Of special note is the study by Kim and Adolph (22), who prepared numerous nitronates by alkylation of salts of dinitromethane, cyanodinitromethane, and trinitromethane with a representative series of a-chloro-substituted (including functionalized) ethers. 

Both C-alkylation products and the corresponding O-alkyl nitronates were detected in the reaction mixture prepared by the reactions of above mentioned salt with primary alkyl halides (Scheme 3.9, Eq. 1). However, isoxazolidines (1) are the main identified products of the reactions with secondary or tertiary alkyl halides. The possible pathway of their formation is shown in Scheme 3.9. Here, the key event is generation of the corresponding olefins from alkyl halides. These olefins can be trapped with O-nitronates that are simultaneously formed in [3 + 2]-cycloaddition reactions. Presumably, these olefins are generated through deprotonation of stabilized cationic intermediates (see Scheme 3.9). 

Nitronate salts can react with alkyl halides to yield polynitroaliphatic compounds with varying degrees of success. The main by-products of these reactions arise for competitive 0-alkylation. Alkyl nitrates are formed as by-products when the nitroform anion is used in these reactions. ... 

Poor to modest yields of trinitromethyl compounds are reported for the reaction of silver nitroform with substituted benzyl iodide and bromide substrates. Compounds like (36), (37), and (38) have been synthesized via this route these compounds have much more favourable oxygen balances than TNT and are probably powerful explosives." The authors noted that considerable amounts of unstable red oils accompanied these products. The latter are attributed to O-alkylation, a side-reaction favoured by an SnI transition state and typical of reactions involving benzylic substrates and silver salts. Further research showed that while silver nitroform favours 0-alkylation, the sodium, potassium and lithium salts favour C-alkylation." The synthesis and chemistry of 1,1,1-trinitromethyl compounds has been extensively reviewed. The alkylation of nitronate salts has been the subject of an excellent review by Nielsen." ... 

Kaplan and Shechter found that certain oxidants react with the nitronate salts of secondary nitroalkanes to yield vic-dinitroalkanes (111) in a reaction referred to as oxidative dimerization. These reactions are believed to involve transfer of an electron from the secondary alkyl nitronate to the oxidant with the production of a nitroalkyl radical. The radical can then dimerize to the corresponding vtc-dinitroalkane (111) (Equation 1.2) or lose nitric oxide to form a ketone via the Nef reaction (Equation 1.3). Unfortunately, formation of the ketone is a major side-reaction during oxidative dimerization and is often the major product. 

The intermolecular alkylation of metallo nitronates with various alkyl halides is limited. The addition of methyl iodide to the silver salt of an aryl nitro-methane provides the corresponding methyl nitronate in moderate yield (Eq. 2.13) (150), which has also been extended to the silver salt of trinitromethane (Scheme 2.16) (151-153). However, in the case of primary halides, both O- and C-alkylation are observed. For secondary and tertiary halides, only O-alkylation is observed, but in low yields. Unfortunately, under the reaction conditions, the starting alkyl halide can undergo dehydrohalogenation to provide the corresponding alkene, which then undergoes [3+2] cycloaddition with the alkyl nitronate. 

Reaction at the C atom of nitronate salts is known with a variety of electrophiles, such as aldehydes (Henry reaction) and epoxides (191-193). Thus the incorporation of the nitro moiety and the cyclization event can be combined into a tandem sequence. Addition of the potassium salt of dinitromethane to an a-haloaldehyde affords a nitro aldol product that can then undergo intramolecular O-alkylation to provide the cyclic nitronate (208, Eq. 2.17) (59). This process also has been expanded to a-nitroacetates and unfunctionalized nitroalkanes. Other electrophiles include functionalized a-haloaldehydes (194,195), a-epoxyaldehydes (196), a-haloenones (60), and a-halosulfonium salts (197), (Chart 2.2). In the case of unsubstituted enones, it is reported that the intermediate nitronate salt can undergo formation of a hemiacetal, which can be acetylated in moderate yield (198). 

Preparation of gem-Dinitroalkanes. A methanolic solution of alkali metal hydroxide (Li, Na, or K) was treated with 10% excess nitroalkane and stirred for 30 minutes. The solution was evaporated to dryness in vacuo, and the alkali metal alkyl nitronate was aned over phosphorus pentoxide at reduced pressure (0.1 mm.) for 24 hours. (Caution nitronate salts may be shock sensitive and have been known to explode after prolonged storage.) A slurry of 3.3 grams (0.02 mole) of lithium 1-nitro-cyclohexane in 50 ml. of acetonitrile was cooled to —40°C., and 2.7 grams (0.02 mole) of nitronium tetrafluoroborate were slowly added. The reaction was not exothermic, and the reaction mixture turned brilliant blue upon adding nitronium tetrafluoroborate. The reaction mixture was stirred for 2 hours at —30° to —40°C., then filtered to give a quantitative yield of lithium tetrafluoroborate. The filtrate was quenched into 100... 

MacMillan s imidazolidinone salts, used successfully in the organocatalysed Diels-Alder reaction (see Section 8.1) also function as effective catalysts in the asymmetric nitrone cycloaddition with simple monodentate dipolarophiles. Thus acrolein (8.63) and crotonaldehyde (8.99) both react with acyclic C-aryl, N-benzyl nitrones and C-aryl N-alkyl nitrones such as (8.198) with high ees ranging from 90 to 99% in the presence of the perchlorate salt of imidazolidinone (8.91). 

As substitution of a-bromoesters with benzaldoxime (187) proceeds with inversion, D-N-hydroxyphenylalanine (34) had been obtained in this way 188). Benzyl and /7-nitrobenzyl nitrone esters (212) may also be obtained 183) by alkylation of triethylammonium nitrone salts (190) (Scheme 40). 

Properties and Preparation of Nitronates Nitroalkanes exist in equilibrium with a tautomeric form known as a nitronic acid (Scheme 16.19) [103]. The aci-form is usually present in minor concentration with an equilibrium constant of 10 [104]. Salts of nitronic acids, metal nitronates, are formed upon deprotonation of nitroalkanes and are potent nucleophiles [105]. Alkylation of the nitronate salts leads to both a-substituted nitro compounds and the isomeric nitronate esters. 

Reaction of 2-chloromethyl-4//-pyrido[l,2-u]pyrimidine-4-one 162 with various nitronate anions (4 equiv) under phase-transfer conditions with BU4NOH in H2O and CH2CI2 under photo-stimulation gave 2-ethylenic derivatives 164 (01H(55)535). These alkenes 164 were formed by single electron transfer C-alkylation and base-promoted HNO2 elimination from 163. When the ethylenic derivative 164 (R = R ) was unsymmetrical, only the E isomer was isolated. Compound 162 was treated with S-nucleophiles (sodium salt of benzyl mercaptan and benzenesulfinic acid) and the lithium salt of 4-hydroxycoumarin to give compounds 165-167, respectively. 

This homoenolate methodology has been extended to the use of nitrones 170 as electrophiles [72]. Scheldt and co-workers have shown that enantiomerically enriched y-amino esters 172 can be prepared with excellent levels of stereocontrol from an enal 27 and a nitrone 170 using the NHC derived from triazolium salt 164 (Scheme 12.37). The oxazinone product 171, formally a result of a [3-1-3] cycloaddition, is cleaved to afford the y-amino ester product 172. The reaction shows broad substrate scope, as a range of substituted aryl nitrones containing electron donating and withdrawing substituents are tolerated, while the enal component is tolerant of both alkyl and aryl substituents. 

Nucleophilic addition of methyl- or phenylphosphite n -butyl- esters to oxo-imine salts, generated by nitrone alkylation of triethyloxoniumtetrafluoro borate (Meerwein salt), leads to a-aminophosphinic acid esters (Scheme 2.201) (691). 

The UV spectra of nitronates, which are not functionalized at the a-C atom, have an intense absorption at 230 to 240 nm, which is very similar in characteristics to UV absorption of salts of nitro compounds and solutions of aci-nitro compounds in protic solvents. Since standard alkyl- or silyl nitronates cannot have ionic structures, the presence of the above mentioned absorption in the UV spectra of nitronates, unambiguously confirms, that these compounds have the structures of O-esters. 

Treatment of sodium and potassium nitronates with alkyl halides typically results in the formation of oximes and carbonyl compounds by cleavage of the N—O bond (11). In one case, however, reaction of w-butyl bromide with the potassium salt of nitro ester 191 does afford the -butyl nitronate (192, Eq. 2.14) (154). 

TV-Hydroxyglycine was obtained in 1896 by acidolysis of the nitrone resulting from the condensation of awd-benzaldoxime 17 with chloroacetic acid 22 N-Alkylation of 17 with a-bromoesters was extended much later to the synthesis of various TV-hydroxyamino acids 23,24 It is notable that syn-benzaldoxime is O-alkylated under the same conditions 25 As substitution of a-bromoacids proceeds with inversion of configuration, Liberek and Palacz 26 prepared H-D-(OH)Phe-OH from (.S )-c/.-bromo-p-phenylpropanoic acid, obtained by HN02 deamination of L-Phe in the presence of KBr. Treatment of nitrone 19 with an TV-hydrox-ylamine salt yields the corresponding TV-hydroxyamino ester 20 (Scheme 5) 24,27 ... 

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