Nitroalkenes Subject

The tandem [4+2]/[3+2] cycloaddition of nitroalkenes is an extremely flexible method for the synthesis of necins. All of the stereochemical attributes are subject to a high level of... 

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). 

Reaction of nitromethane and monosaccharide-derived dialdehydes is a useful tool that has been broadly used for the preparation of nitro and amino sugars, and carbocycles.30 Dialdehydes can easily be obtained by oxidative cleavage of conveniently protected monosaccharides with sodium periodate. Their subsequent Henry reaction with a nitroalkene, commonly nitromethane, usually gives isomeric mixtures that require the isolation of the major isomer.31 Thus, treatment of the D-ribose derivative 27 with sodium periodate gave dialdehyde 28, which was subjected to a Henry reaction with nitromethane, to afford nitrosugar 29 as an epimeric mixture (Scheme 11).32... 

As a consequence of the complimentary electron demand of the nitroalkene and the product nitronate, there exists the possibility of a one-pot, tandem reaction. In this case, the nitroalkene will react preferentially with the electron-rich alkene to produce an intermediate nitronate. This nitronate can then react with a second alkene bearing an electron-withdrawing substituent. Therefore subjection of the nitroalkene 210 to both ethyl vinyl ether and acrylonitrile provides only the nitroso acetal 211 in moderate yield (Eq. 20) (70). Moreover, this also allows the possibility of intramolecular variants of the process. 

Shibasaki and co-workers used an intramolecular nitrile oxide cycloaddition to prepare the skeleton of phorbol (272) (Scheme 6.99), a tumor promoter that activates protein kinase C (PKC) (333). Nitroalkene 268 was elaborated in several steps from (+)-3-carene (267) and was subjected to cycloaddition by means of -chlorophenyl isocyanate-triethylamine to give cycloadduct 269 in 88% yield. Reductive hydrolysis employing Raney Ni and boric acid afforded hydroxyketone 270, that was subsequently used for the construction of the optically active derivative 271, which contains the phorbol skeleton (333). 

The effect of an internal allylic asymmetric center on the course of the intramolecular cycloaddition reaction has been studied (82TL2081). Subjection of the (Z)-nitroalkene (238) to phenyl isocyanate-triethylamine led to the desired cycloaddition product (240) in high yield (>98% purity), whereas the corresponding (E)-nitroalkene gave a 3 1 mixture of two cycloadducts. These results are understandable in terms of A1,3 strain present in the transition state for cycloaddition (68CRV375). For the cis- alkene (238), one mode of cycloaddition (241) would involve a severe Me-Me interaction whereas the other (239) contains a less serious Me-H interaction (82TL2081). 

The synthesis of the bisbenzannelated spiroketal core of the y-rubromycins was achieved by the research team of C.B. de Koning." The key step was the Nef reaction of a nitroolefin, which was prepared by the Henry reaction between an aromatic aldehyde and a nitroalkane. The nitroolefin was a mixture of two stereoisomers, and it was subjected to catalytic hydrogenation in the presence of hydrochloric acid. The hydrogenation accomplished two different tasks it first converted the nitroalkene to the corresponding oxime and removed the benzyl protecting groups. The oxime intermediate was hydrolyzed to a ketone that underwent spontaneous spirocyclization to afford the desired spiroketal product. 

The Cu(II) complex of 117 outperforms the congener possessing a BINOL moiety in conjugate addition of organometallics to nitroalkenes, the o,o -dioxydiphenylmethane unit is subject to conformational changes as determined by the bis-(a-phenethyl)amino chirality/ ... 

The in situ generation of TV-vinyl-AT-cyclohexylnitrosonium cations from the corresponding a-chloro nitrone, e.g., AT-(2-chloroethylidene)cy-clohexylamine N-oxide (25), and their subsequent [4+ + 2] cycloaddition with electron-rich, neutral, or selected electron-deficient dienophiles have been extensively investigated (Scheme 9-1X).173-175 The intermediate im-inium salts which are derived from the regio- and stereoselective [4+ + 2] cycloadditions are not generally isolated but are subjected to the useful transformations illustrated in Scheme 9-IX. The intramolecular [4+ + 2] cycloadditions of vinylnitrosonium cations and nitroalkenes have been detailed.176... 

Acetylacetone has also been the subject of several studies when used as 1,3-dicarbonyl compound suitable to engage in a Michael reaction with nitroalkenes under H-bonding catalysis. In this context, Takemoto s catalyst 68a and valine-derived thiourea 74 have been tested in the reaction with acetylacetone with nitrostyrene furnishing good results, although no extensive study was carried out in order to evaluate the substrate scope with regard to the substitution at the nitroalkene. On the other hand, several functionalized thioureas have been expressly surveyed in this reaction, providing a detailed study... 

When the nitroalkene 125 was subjected to the three-step procedure of Michael addition of propargyl alcohol, Henry reaction, and intramolecular radical cyclization, the Incyclic structure 126 was obtained,... 

Shortly after, Waldmann and co-workers reported the first efficient Cu(I)-catalyzed highly diastereoselective and enantioselective[3-1-2] cycloaddition reaction of S-shaped 1,3-fused cyclic azomethine ylides with nitroalkenes, providing an unprecedented and general access to functionalized tropane scaffolds bearing quaternary and tertiary stereocenters in a stereoselective manner (Scheme 16) [28], Furthermore, subjecting a collection of these tropane derivatives to a cell-based screen revealed a novel class of hedgehog signaling inhibitors. 

Axially chiral bis-arylthiourea-based organocatalyst (6) has been developed and subjected to Friedel-Crafts type addition of indole and N-methyl pyridine to nitroalkenes (Scheme 2.31) [82]. 

As illustrated in Figure 16.7, an intramolecular [4 + 2] nitroalkene cycloaddition can be followed by an intermolecular [3 + 2] cycloaddition of the formed nitronate intermediate. This variant of the tandem cycloaddition has not been extensively studied and only two reports can be found. Moreover, the resulting nitroso acetals have not been subjected to further transformations such as hydrogenolysis. 

Cycloaddition precursor 167 was prepared through displacement of the chloride of chlorosilyldiene 166 with potassium nitroacetaldehyde. The nitroalkene 167 was then subjected to the MAPh-promoted [4-1-2]-cycloaddition with S,2R) isomer of 2-phenylcyclohexyl vinyl ether 168 affording trans nitronate 170 with excellent diastereofacial selectivity (SilRe = AAI ). The nitronate 170 resulted from an exclusively exo approach of s-fraws -configured vinyl ether 168 to the Si face of nitroalkene 167 establishing the S configuration at Cl of castanospermine 173 (Scheme 16.25). 

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