Methylenes nitroalkenes

When a-tethered nitroalkenes bearing three or four methylene chains and ester-activated dipolarophiles react with vinyl ethers, spiro mode tandem cycloaddition takes place to give tricyclic spiro nitroso acetals in good yield and high diastereoselectivity (Scheme 8.46).184... 

Individual aspects of nitrile oxide cycloaddition reactions were the subjects of some reviews (161 — 164). These aspects are as follows preparation of 5-hetero-substituted 4-methylene-4,5-dihydroisoxazoles by nitrile oxide cycloadditions to properly chosen dipolarophiles and reactivity of these isoxazolines (161), 1,3-dipolar cycloaddition reactions of isothiazol-3(2//)-one 1,1-dioxides, 3-alkoxy- and 3-(dialkylamino)isothiazole 1,1-dioxides with nitrile oxides (162), preparation of 4,5-dihydroisoxazoles via cycloaddition reactions of nitrile oxides with alkenes and subsequent conversion to a, 3-unsaturated ketones (163), and [2 + 3] cycloaddition reactions of nitroalkenes with aromatic nitrile oxides (164). 

Alkenes react with dinitrogen pentoxide in chlorinated solvents to give a mixture of /3-nitro-nitrate, vic-dinitro, vic-dinitrate ester and nitroalkene compounds. At temperatures between -30 °C and -10 °C the /3-nitro-nitrate is often the main product. The /3-nitro-nitrates are inherently unstable and readily form the corresponding nitroalkenes." Propylene reacts with dinitrogen pentoxide in methylene chloride between -10 °C and 0°C to form a mixture of l-nitro-2-propanol nitrate (27 %) and isomeric nitropropenes (12 %). The same reaction with cyclohexene is more complicated." ... 

Solutions of nitric acid in chlorinated solvents can add to some alkenes to give nitrate esters. Some tertiary nitrate esters can be prepared in this way isobutylene (49) reacts with fuming nitric acid of 98.6 % concentration in methylene chloride to give ferf-butyl nitrate (50). However, the products obtained depend on both the substrate and the reaction conditions /3-nitro-nitrate esters, vic-dinitrate esters, /3-nitroalcohols and nitroalkenes have been reported as products with other alkenes. Oxidation products like carboxylic acids are also common, especially at elevated temperatures and in the presence of oxygen. The reaction of alkenes with fuming nitric acid is an important route to unsaturated nitrosteroids, which assumedly arise from the dehydration of /3-nitroalcohols or the elimination of nitric acid from /3-nitro-nitrate... 

Spurred by these observations, we examined a relevant application of the method for nitrocyclopropane synthesis from nitroalkenes and dimethylsulfoxonium methylide (17), Equation 3. It had previously been employed for the synthesis of a 2,3-dideoxv-2,3-C-methylene-3-nitro-hexopyranoside, the first one of the small number of carhohvdrates containing the nitrocyclopropane structure thus far known (18). 

Treatment of the known nitroalkene 44 with the ylide indeed gave 41, but it was accompanied by a small proportion of the stereoisomer 4 (lA). Altljough the preparative yield was low (- <30%), the high diastereofacial selectivity of the methylene addition was remarkable. It becomes plausible on inspection of a molecular model, which points to hindered approach from one face, and unhindered approach from the other (Figure 7). 

Interestingly, bis(methylthio)-l-nitroethylene (380) reacts with dimetallic zinc-copper species leading to the corresponding exo-methylene cycloalkenes, such as 381 (Scheme 100) . / -Disubstitutcd nitroolefins are especially difficult to prepare by nitroaldol condensation. The addition of zinc-copper reagents to nitroolefins followed by a reaction with phenylselenyl bromide produces, after IFO, oxidation, EtZ mixtures of -disubstituted nitroalkenes, such as 382 (Scheme 100) . 

The relative trans stereochemistry of the substituents in the tetrasubstituted 3,4-dihydro-27/-thiopyran 85, an intermediate isolated from the [4+2] cycloaddition between an enaminothione and a nitroalkene, has been established by H NMR spectroscopy <1994JPR434>. The methylene units of 5-(diethylphosphono)-3,4-dihydro-277-thiopyran 86 appear as multiplets in the range 2.0-2.8 ppm and the vinyl proton (H-6) displays coupling to the P atom with V= 21.6Hz <20050BC924>. 

Yuan, C., and Li, C., SIndies on organophosphorus compounds. Part 67. Reactions of a-nitroalkenes with compounds bearing active methylene groups. A novel and convenient synthesis of 2-isoxazoline derivatives, Phosphorus, Sulfur Silicon Relat. Elem., 78, 47, 1993. 

Oxa- and aza-Michael additions followed by intramolecular cyclizations occur when propargyl alcohols are treated with a, -unsaturated nitroalkenes in the presence of t-BuOK in THF. Although exo-3-methylene tetrahydrofurans are usually the major products of these reactions, 3,4-dihydropyrans are also obtained in some cases, depending upon the substituents present within the donor and acceptor. Equation 59 shows the results of the reactions of propargyl alcohol with four nitroalkenes. Similar reactions of methyl propargylamine with these same acceptors give exclusively 3-methylenepyrrolidines."... 

Nitroalkenes as Acceptors. The organocatalytic asymmetric Michael addition of activated methylenes to nitroalkenes is an important carbon-carbon bond-forming reaction, which provides access to synthetically useful enantioen-riched nitroalkanes. In 2003, Takemoto and co-workers [77] disclosed the first highly... 

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