Nitro compounds from alkenes

A more efficient and economic procedure for the preparation of / -acetamido nitro compounds from alkenes, conjugated dienes and silyl enol ethers is based on the electrochemical generation of nitronium tetrafluoroborate in acetonitrile solution by anodic oxidation of dinitrogen tetrox-ide, using a divided cell (Table 6, Method B)142-143. From 1,3-dienes, mixtures of regio- and diastereomers were obtained. 

The two major methods of preparation are the cycloaddition of nitrile oxides to alkenes and the reaction of a,/3-unsaturated ketones with hydroxylamines. Additional methods include reaction of /3-haloketones and hydroxylamine, the reaction of ylides with nitrile oxides by activation of alkyl nitro compounds from isoxazoline AT-oxides (methoxides, etc.) and miscellaneous syntheses (62HC(i7)i). 

Isoxazolines A-oxides have been synthesized from primary aliphatic nitro compounds and alkenes by a two-step procedure consisting of 1,3-DC of a 1-halo-substituted silyl nitronate followed by halosilane elimination <06S2265>. 

Metal salts or complexes have a role in promoting dehydration of nitro compounds. Thus, 5-phenylisoxazole has been obtained in low yield from the lithium salt of phenylacetylene with nitromethane in dioxan at room temperature [24]. The complex tetrakis(triphenylphosphane) platinum(O) on treatment with nitromethane leads to fulminatobis(triphenylphosphane)platinum(II), possibly via CT-nitromethyls [25-27]. Cerium and other metal nitrates have been claimed to promote condensation of nitro compounds with alkenes [28]. More examples of condensations caused by transition metal salts are reported in Section 8.2.4. 

Various terminal allylic compounds are converted into l-alkenes at room temperature[362]. Regioselective hydrogenolysis with formate is used for the formation of an exo-methylene group from cyclic allylic compounds by the formal anti thermodynamic isomerization of internal double bonds to the exocyclic position[380]. Selective conversion of myrtenyl formate (579) into /9-pinene is an example. The allylic sulfone 580 and the allylic nitro compound... 

As discussed in Section 6.2, nitro compounds are good precursors of nitrile oxides, which are important dipoles in cycloadditions. The 1,3-dipolar cycloaddition of nitrile oxides with alkenes or alkynes provides a straightforward access to 2-isoxazolines or isoxazoles, respectively. A number of ring-cleaving procedures are applicable, such that various types of compounds may be obtained from the primary adducts (Scheme 8.18). There are many reports on synthetic applications of this reaction. The methods for generation of nitrile oxides and their reactions are discussed in Section 6.2. Recent synthetic applications and asymmetric synthesis using 1,3-dipolar cycloaddition of nitrile oxides are summarized in this section. 

Nitroalkanes react with Jt-deficient alkenes, for example, p-nitro ketones are produced from a,P-unsaturated ketones [41], whereas allylic nitro compounds have been prepared via the Michael-type addition of nitroalkanes with electron-deficient alkynes (Table 6.19). The reaction in either dimethylsulphoxide [42] or dimethyl-formamide [43] is catalysed by potassium fluoride in the presence of benzyltriethyl-ammonium chloride the reaction with dimethyl acetylenedicarboxylate is only successful in dimethylsulphoxide [42], Primary nitroalkanes produce double Michael adducts [42,44], A-Protected a-aminoacetonitriles react with alkynes under catalysed solidiliquid conditions to produce the Michael adducts [45] which, upon treatment with aqueous copper(Il) sulphate, are converted into a,p-unsaturated ketones. 

A large part of the usefulness of the Michael reaction in organic synthesis derives from the fact that almost any activated alkene can serve as an acceptor7—a, 3-unsaturated ketones, esters, aldehydes, amides, acids, lactones, nitriles, sulfoxides, sulfones, nitro compounds, phosphonates, phosphoranes, quinones,... 

Allylic nitro compounds containing a suitable dipolarophile undergo Diels-Alder cycloaddition to alkenes in the presence of tin(lV) chloride affording cyclic nitronic esters (Scheme 16).26 Nitronic ester (59) could not be isolated but spontaneously cyclized to the 5,5-fiised cyclic product (60), isolated in 68% yield. The nitronic esters (61a) and (61b) were isolated from the Diels-Alder reaction and could be separated. Heating (61a) in refluxing benzene afforded the 5,6-fused dipolar cydization product (62a) in 93% (68% overall) yield (61b) likewise afforded (62b) in 62% (11% overall) yield. Either (62a) or (62b) could be converted to the tricyclic lactam (63) by catalytic hydrogenolysis followed by lactamiza-... 

Macro carbocyclic rings can be constructed by cyclization of nitrile oxides derived from oj-nitro-l-al-kenes (Scheme 22). If the intervening bridge is not longer than seven atoms, only fused bicyclic products are obtained. Thus, the nitrile oxide derived from nitro compound (75a) is cyclized in 44% yield to the 5,9-fused bicyclic isoxazoline (76a).38 10-Nitro-l-decene (75b) also cyclized to (76b) in unspecified yield.39 It should be noted that these results go counter to the usual regiochemistry of an intermolecular nitrile oxide cycloaddition where the five-substituted isoxazoline is usually,27 although not always,40 heavily preferred from reaction of a terminal alkene. Thus, geometric constraints have won out over the normal electronic control. 

Experimental evidences suggest that nitrile oxides are not reaction intermediates and water is released from the nitro compound after reaction with the alkene <07SL2451>. A rationalization of the condensation of primary nitro compounds with alkynes and alkenes under base catalysis has been proposed <07EJO4352>. 

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