Nitroethylene, reactions

Unsaturated compounds activated by electron-attracting groups can also effect alkylation at the 3-position. An important example is the reaction with nitroethylene to form 3-(2-nitroethyl)indole [31731-23-4] (14). 

Other methods of generating a-aminoketones in situ are common, if somewhat less general than the methods already described. 2-Nitrovinylpyrrolidine, which is readily available, yields 2,3-bis(3-aminopropyl)pyrazine on reduction and this almost certainly involves ring opening of the intermediate enamine to an a-aminoketone which then dimerizes under the reaction conditions (Scheme 59) (78TL2217). Nitroethylene derivatives have also served as a-aminoketone precursors via ammonolysis of the derived epoxides at elevated temperatures (Scheme 60) (76S53). Condensation of 1,1-disubstituted hydrazine derivatives with a-nitro-/3-ethoxyethylene derivatives has been used in the synthesis of l,4-dialkylamino-l,4-dihydropyrazines (Scheme 61) (77S136). 

Nitroisoxazoles have been synthesized by reaction of l-chloro-2-nitroethylene with nitrile N-oxides (75C350). 

Nitroolefins also offer the possibilities of 1,2 cycloaddition (37,57) or simple alkylation (57-59) products when they are allowed to react with enamines. The reaction of nitroethylene with the morpholine enamine of cyclohexanone led primarily to a cyclobutane adduct in nonpolar solvents and to a simple alkylated product in polar solvents (57). These products are evidently formed from kinetically controlled reactions since they cannot be converted to the other product under the conditions in which the other... 

Indole magnesium iodide reacts with nitroethylene to give 3-(2-nitroethyl)indole (351) in good yield (Noland and Hartman ). Noland et al. subsequently showed that this reaction, which is usually carried out in ether at 0°, was of general applicability and reported... 

The Michael type reaction of f3/f -5-r-butyldimethysiloxy-3-phenyl-l//-pyrrolo[l,2-c oxa2ole with nitroethylene proceeds in the presence of Lev/is acid to give the alkylated product in good chemical yield and diastereoselecdvity In the case of nitroethylene, the Diels-Alder type transition state is favored to give the ryu-adduct selectively fEq 4 72 ... 

Sequential radical cyclizations are also featured in an efficient and clever synthesis of the cedrane framework 83 (see Scheme 15).30 Compound 81, the product of a regioselective Diels-Alder reaction between isoprene (79) and nitroethylene (80), participates in a nitroaldol reaction (Henry reaction) with 5-methyl-4-hexenal in the presence of a basic resin to give 82. Because the nitro group in... 

Dehydration of P-nitro alcohols provides an important method for the preparation of nitroalkenes. Because lower nitroalkenes such as nitroethylene, 1-nitro-1-propene, and 2-nitro-l-propene tend to polymerize, they must be prepared carefully and used immediately after preparation. Dehydration with phthalic anhydride is the most reliable method for such lower nitroalkenes.42,43 Such lower nitroalkenes have been used as important reagents for Michael acceptors or dienophiles in the Diels-Alder reaction, which will be... 

Ono and coworkers have devised a new acetylene equivalent for the Diels-Alder reaction namely, l-phenylsulfony-2-nitroethylene is a very reactive dienophile, and the radical elimination from the adduct gives the Diels-Alder adduct of acetylene, as exemplified in Eq. 7.113. Other acetylene equivalents are summarized in a review.156... 

The Diels-Alder reaction of morphinan-6,8-dienes with nitroethene affords a novel type of opium alkaloids (Eq. 8.3).10a High reactivity of nitroethylene is demonstrated for the Diels-Alder reaction with thermally unstable dienes, and this is used for synthesis of polycyclic kopsane-like alkaloids.1013... 

The total synthesis of frodosin B, which is a potentially useful drug for HIV, has been reported (Scheme 8.8). The key steps in the synthesis are a Friedel-Crafts reaction to form the seven-membered ring and a Diels-Alder reaction of nitroethylene to build the six-membered ring, thereby fixing the double bond in the proper position.44... 

If X = AcO, intermediate SENA can be trapped by methyl acrylate in the [3+ 2]-cycloaddition reaction (isoxazolidine (416)). If X=C1, attempts to trap silyl nitronate failed however, nitroethylene was detected in a Diels-Alder reaction. By contrast, SENAs, in which X=OSiMe3 or NHPh, are quite stable. Therefore, the substituents X can be arranged in the following series of increasing elimination rates of SiX Cl > AcO > > PhNH. 

Papai et al. selected as model reaction the addition of 2,4-pentanedione (acetylacetone) to trans-(R)-mtrostyvQnQ, catalyzed by the bifunctional thiourea catalyst shown in Scheme 6 [46]. The analogous Michael-addition involving dimethyl malonate and nitroethylene as substrates, and a simplified catalyst was calculated at the same level of theory by Liu et al. [47]. Himo et al. performed a density functional study on the related cinchona-thiouTQa catalyzed Henry-reaction between nitromethane and benzaldehyde [48]. 

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) . 

Tryptamines can also be obtained from nitroethyl and nitrocthcnyl indoles. 3-(2-Nitroethyl)indolcs can be obtained in moderate to good yield by 3-alkylation with nitroethylene. The effective generation of this reactive alkene is the key to the success of the procedures. Ranganalhan and co-workers generated nitroethylene from a mixture of nitroethanol and phthalic anhydride heated to 175 -180 C. Nitroethylene was obtained by distillation at partial vacuum. Reaction of nitroethylene with indole gave 3-(2-nitroethyl)indole in 80% yield[8]. Another procedure involves in situ generation of nitroethylene from 2-nitroethyl acetate. This can be done in refluxing xylene in the presence of a radical chain inhibitor (c.g. ferf-butylcatcchol)[9]. 

Reaction 4 is favored by the strong electron affinity of nitroethylene (30). The carbanion may be formed by ion-molecule reaction between the anion radicals and the nitroethlene molecules (reaction 5), to which the latter add successively, and polymerization proceeds by anionic propagation (reaction 6)... 

In contrast to the reactivity of the nitroethylenes, acrylonitrile generally reacts with indoles to form the l-(2-cyanoethyl) derivatives (B-70MI30500,79MI30501), whereas Michael addition at the 3-position requires the catalytic effect of copper(II) salts. The addition-elimination reaction of pyrroles and indoles with l,l-dicyano-2-ethoxyethylene proceeds in low yield (<30%) to give the dicyanovinyl derivatives, which can be converted by standard procedures into the formyl compounds (81H(16)1499). Tetracyanoethylene forms charge transfer complexes with indoles, which collapse to the Michael adduct anions and subsequently eliminate a cyanide ion with the formation of the tricyanovinylindole (B-70MI30500). 

Thus, if you look at the different dienophiles in Fig. 2.1, the dimerization of butadiene 2.1 is slower than its reaction with acrolein 2.4. Methyl acrylate and methyl vinyl ketone have electron-withdrawing substituents Z of comparable power, and react at a similar rate, but cyclohexenone 2.5, which has a (5-alkyl substituent, is considerably less reactive. Nitroethylene has one of the most powerful electron-withdrawing groups, and is a very good... 

The reactivity and regioselectivity of 1-azidoadamantane (See Scheme 18), a bridgehead azide, have been investigated with electron-poor olefins.155 The reaction with ethyl acrylate proceeds smoothly at 25°C to afford exclusively the 4-substituted triazoline in good yield the regiochemistry is supported by 13C- and H-NMR spectral data. /S-Nitrostyrene and nitroethylene give only triazoles. 

A further example of an imbalance reduction is seen in the reaction 1-benzyl-l-methoxy-2-nitroethylenes (47-Z) with secondary alicyclic amines in 50% DMSO-50% water (v/v).103... 

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