Nitronic esters, cyclic—

Deoxygenation of Cyclic Nitronates Since cyclic nitronates are readily available and are rather stable compounds (see Sections 3.2 and 3.3), simple approaches for their deoxygenation with retention of the configuration of stereocenters can be used for the synthesis of cyclic esters of functionalized oximes. 

Aside from the relatively trivial conversions of nitronates to the corresponding oxime and carbonyl compounds (10,11), the chemistry of nitronates remained relatively unexplored for much of the early 1900s. However, in 1964, Tartakovskii et al. (12) demonstrated that alkyl nitronate esters were competent partners in the newly discovered class of dipolar cycloadditions with alkenes (Scheme 2.1). Both cyclic and acyclic nitronates participated, thus providing a new functional group were the nitrogen atom existed at the center of an acetal (13). These compounds were subsequently referred to as nitroso acetals (14) or nitrosals (15). 

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-... 

Carbamoyl nitroso dienophiles, derived from chiral pyrrolidines, have been generated and their reactivity with cyclohexa-diene investigated. Using (—)-fra/w-2,5-dimethylpyirolidine as the auxiliary, the [4 + 2] cycloadduct is isolated in 82% yield and with 98% diastereomeric excess (eq 10). Similarly, chiral ynamine dienophiles have been utilized in asymmetric [4 + 2] cycloadditions with a,p-unsaturated nitroalkenes to afford cyclic nitronic esters. The resulting esters subsequently undergo a rapid [1,31-rearrangement to afford chiral cyclic nitrones in moderate yield and high diastereoselectivity (eq 11)-... 

IsoxazoUne iV-oxides reflect in their characteristics both as a heterocyclic isoxazoline ring as well as cyclic nitronic ester. As a nitronic ester they can undergo 1,3-dipolar cycloaddition with even... 

Quinoxaline-2-carboxaldehyde has been converted into the 2-carboxylic acid by oxidation with potassium permanganate in acetone and reduced to the 2-hydroxymethyl compound by treatment with formalin and potassium hydroxide. It also undergoes other typical reactions of aromatic aldehydes such as benzoin formation on reaction with potassium cyanide - and condensation reactions with malonic acid and its diethyl ester and Schiff base formation. Acid-catalyzed reaction of quinoxaline-2-carboxaldehyde with ethylene glycol gives the cyclic acetal the diethylacetal has been prepared by reaction of 2-dibromomethylquinoxaline with sodium ethoxide. " An indirect preparation of the oxime 11 is achieved by treatment of 2-nitromethyl-quinoxaline (10) with diazomethane followed by thermolysis of the resulting nitronic ester. 

Reactions of cyclic nitronic esters are also described. 3-Nitro-isoxazoline-jV-oxide (32a) is itself a cyclic nitrone, and forms isoxazo lizidines (33a) when allowed to react with olefins (5) such as ethylene,112,129,130 vinyl acetate,129 propylene,129 and styrene.130 With tetramethylethylene, cyclopentene, and cyclohexene, the corresponding isoxazolizidines are also obtained.131... 

Six-membered cyclic nitronic esters, the 4//-5,6-dihydrooxazine-jV-oxides (35), exhibit much the same reactivity as their five-membered analogs. Reactions with styrene, methyl acrylate, and allyl alcohol give isoxazolidines of type 1.133... 

Nitronic acid esters, cyclic s. 4H-l,2-Oxazine 2-oxide ring, 5,6-dihydro-Nitronitiic acid esters... 

Kumaran G, Kulkami GH. Effect of the a-alkyl substituent of conjugated nitroolefins on the formation of cyclic nitronic esters vs. nitrocyclopropanes in their reaction with sulfur ylides. Synthesis 1995 1545-1548. 

Cycloaddition of the cyclic nitrone derived from proline benzyl ester with alkenes proceeds readily to give isoxazolidines with good regio-and stereoselectivity (Eq. 8.47).68 The reaction favors exo-mode addition. However, certain cycloadditions are reversible and therefore the product distribution may reflect thermodynamic rather than kinetic control. 

The chemistry of a-haloketones, a-haloaldehydes and a-haloimines Nitrones, nitronates and nitroxides Crown ethers and analogs Cyclopropane derived reactive intermediates Synthesis of carboxylic acids, esters and their derivatives The silicon-heteroatom bond Syntheses of lactones and lactams The syntheses of sulphones, sulphoxides and cyclic sulphides... 

Aldol-type reactions of nitrones (303) occur with electron-deficient ketones, such as a-keto esters, a, 3-diketones, and trifluoromethyl ketones. These reactions are catalyzed by secondary amines. The use of chiral cyclic amines A1-A7 leads to a-(2-hydroxyalkyl)nitrones (304) in moderate yields and rather high optical purity (Scheme 2.120) (381). The mechanism of the nitrone-aldol reaction of iV-methyl-C-ethyl nitrone with dimethyl ketomalonate in the absence and presence of L- proline has been studied by using density functional theory (DFT) (544). 

Finally, Scheme 3.14 presents the Michael addition of bromomalonic ester to conjugated nitro olefins 10. This approach allows one to synthesize five-membered cyclic nitronates (5) doubly functionalized at the C-5 atom (Scheme 3.14, Eq. 5). 

For example, the reaction of nitronates (123) with a zinc copper pair in ethanol followed by treatment of the intermediate with aqueous ammonium chloride a to give an equilibrium mixture of ketoximes (124) and their cyclic esters 125. Heating of this mixture b affords pyocoles (126). Successive treatment of nitronates (123) with boron trifluoride etherate and water c affords 1,4-diketones (127). Catalytic hydrogenation of acyl nitronates (123) over platinum dioxide d or 5% rhodium on aluminum oxide e gives a-hydroxypyrrolidines (128) or pyrrolidines 129, respectively. Finally, smooth dehydration of a-hydroxypyrrolidines (128) into pyrrolines (130f) can be performed. 

The reactions of ammonia or primary amines with five-membered cyclic nitronates containing the EWG -group at the C-5 atom involve deoxygenation of the nitronate fragment, aromatization of the ring, and amidation of the ester... 

The ester groups in five-membered cyclic nitronates were successfully subjected to different transformations. Treatment of nitronates containing the methoxycarbonyl groups at positions 3 and 5 with butylamine at 20°C afforded the corresponding diamides (237b) (Scheme 3.119, Eq. 2). Their yields depend dramatically on the nature of the substituent R (further transformations of these products are shown in Scheme 3.109). 

The reaction of cyclic nitrone with phenyl isothiocyanate <2003MI253>, isocyanate <1974JOC568>, or cyano-esters <1995JP11417> has been reported. The beneficial effect of activation of the dipolarophile by coordination on a platinum complex and focused microwave irradiation has been described (Scheme 15) <2003JCD2540>. 

Cyclic alkyl nitronates may be used in tandem [4+2]/[3+2] cycloadditions of nitroalkanes, and this reaction has been extensively studied by Denmark et al. (64,333-335). In recent work, they developed the silicon-tethered heterodiene-alkene 219 (Scheme 12.63). Steric hindrance and the fact that both the nitroalkene and the a,p-unsaturated ester in 219 are electron deficient renders the possibility of self-condensation. Instead, 219 reacts with the electron-rich chiral vinyl ether 220 in the presence of the catalyst 224 to form the intermediate chiral nitronate 221. The tandem reaction proceeds from 221 with an intramolecular 1,3-dipolar cycloaddition to form 222 with 93% de. Further synthetic steps led to the formation of ( )-detoxinine 223 (333). A similar type of tandem reaction has also been applied by Chattopadhyaya and co-workers (336), using 2, 3 -dideoxy-3 -nitro-2, 3 -didehydrothymidine as the starting material (336). 

---