Nitroalkenes alkyl-substituted

The preparation of resin-bound nitroalkenes via a microwave-assisted Knoevenagel reaction of resin-bound nitroacetic acid with aryl and alkyl substituted aldehydes is reported. The potential of these resin-bound nitroalkenes for application in combinatorial chemistry is demonstrated by a Diels-Alder reaction with 2,3-dimethylbutadiene (Scheme 8.9). It is also used for one-pot three-component tandem [4+2]/[3+2] reactions with ethyl vinyl ether and styrene 46... 

Keywords Organozinc, Organolithium, Grignard reagent, Copper, Conjugate addition, Nucleophilic addition, Alkylation, Activated olefin, Enone, Nitroalkene, p-Substituted carbonyl... 

In principle nitroalkenes should be available from direct nitration of vinyl carbanions. However, this reaction is not practical due to the potential anionic polymerization. But vinylstannanes obtained from ketones can be used instead of vinyl carbanions. Tetranitromethane is effective in replacing tin by nitro at unsaturated carbon. This method has been used to prepare several alkyl-substituted 1-nitrocyclo-hexenes and 1-nitrocycloheptenes (Scheme 2). ... 

The use of naphthols 145 as the carbon nucleophilic readion component in Friedel-Crafts type Michael addition readions was also reported in 2007 by Chen and coworkers [43], In this system, the pronucleophile is activated by the quinuclidine unit of bifundional cinchona-based thiourea catalysts such as 81a. A range of aryl-and alkyl-substituted nitroalkene derivatives 124 were applicable to this system. The corresponding adducts 146 were obtained with 85-95% ee at low temperature... 

Resin-bound nitroalkenes were synthesized via a Knoevenagel condensation of resin-bound nitro acetic acid with aryl and alkyl substituted aldehyde (Scheme 9.29). In this way an extra site of diversity can be introduced into the cycloaddition products of these nitroalkenes. Furthermore, the resin-bound nitroalkenes can serve as activated alkenes in other cycloaddition reactions (Diels-Alder, 1,3-dipolar cycloaddition, [2 + 2] cycloaddition) and therefore lead to the solid phase synthesis of other interesting compoimd classes (see also Scheme 9.3, Sect. 9.2). Formation of the resin-bound nitroalkenes 73a-e was realized in one step via a microwave-assisted condensation of aldehyde 72a-e (10 equiv.) with the resin-bound nitro acetic acid 71, followed by dehydration of the intermediate y -nitroalcohol [6] (Scheme 9.29). THF was used as the solvent in order to obtain optimal diffusion of the aldehyde in the polystyrene resin. 

Therefore, under the optimized conditions, 9-ep -dihydroquinine-derived thiourea 71a performed very well in the Michael reaction of diethyl malonate with nitroalkenes, furnishing the final compounds with enantioselectivities around 90% ee (Scheme 4.8). Remarkably, this catalyst also seemed to tolerate the use of (3-alkyl substituted nitroalkenes as substrates, furnishing the expected final compounds with only a small decrease in enantioselectivity, although only a few examples were studied in that case. In an independent work, 9-e i-cinchonine-derived thiourea 72b was also reported to be a very efficient catalyst for this reaction, obtaining the final Michael adducts in... 

Racemic 3-alkyl oxindoles have also been found to be useful pro-nucleophiles in this context (Scheme 4.IS)." For this transformation, a modified version of Takemoto s catalyst was identified as the most efficient promoter of the reaction, which was found to have a remarkably wide substrate scope, allowing many different substitution patterns both at the oxindole and at the nitroalkene reagent, and even tolerating well the use of p-alkyl substituted nitroalkenes as Michael acceptors. Yields, diastereo- and enantioselectivities were found to be excellent in almost all the cases studied. The reaction also accepted very well the use of the simple nitroethene, another very challenging... 

Anthracenones are another class of C-H acidic compounds suitable to be employed in this reaction (Scheme 4.16) and, in fact, Takemoto s catalyst has been identified as the most efficient catalyst among a series of different thioureas tested, which also included a family of different cinchona alkaloid-derived candidates." The reaction proceeded satisfactorily for a wide variety of aromatic nitroalkenes tested but poorer results were obtained in the case of the p-alkyl substituted Michael acceptors. 

Michael acceptors, with no example reported regarding the use of p-alkyl substituted nitroalkenes. 

On the other hand, 2-naphthols have been used with different success as Michael donors in conjugate Friedel Crafts reactions with nitroalkenes and related substrates (Scheme 4.53). For example, cinchonine-derived thiourea 72b was identified as an excellent promoter for the reaction of a wide variety of 2-naphthols and nitroolefins, providing excellent yields and enantioselectivities. Remarkably, the more challenging p-alkyl substituted nitroalkenes were also found to undergo the reaction in a highly stereoselective way and with comparable yields to those obtained when nitrostyrene derivatives were employed. 

In 2009, the Rovis group disclosed a remarkable study on the asymmetric intermoleeular Stetter reaction with heteroaromatic aldehydes and p-alkyl substituted nitroalkenes in excellent enantioselectivity. With the novel backbone-fluorinated NHC initially developed by their group, the Stetter reaction products were afforded with up to 99% yield and 96% ee. With detailed conformational analysis of the catalyst and DFT calculations, the authors demonstrated that the gawcAe-effect from the fluorine on the five-membered backbone of the catalyst plays a crucial role on increasing the enantioselectivity dramatically (Scheme 7.29). 

Scheme 7.29 NHC-catal3 ed asymmetric intermolecular Stetter reaction of heteroaromatic aldehydes with p-alkyl substituted nitroalkenes...

In the reactions using NO as a reagent, there is always a problem that the true active species is unidentified. This is due to the possibility that a trace amount of oxygen or a metal ion can function as a catalyst for the reaction of NO. Pure NO does not react with alkenes, for example, isobutene or similar alkyl-substituted olefins [22]. The main isolated products were found to be nitroalkenes, and it was postulated that the small amounts of NO formed from the oxidation of NO ... 

DiaryIprolinol 83 (Figure 24.28) was used in the addition of aldehydes to 3-nitroacrylates and aryl- and alkyl-substituted nitroalkenes [104]. Water was the reaction medium of choice with benzoic acid as additive to improve the reaction rate and diastereoselectivity. Under these conditions high stereoselectivities were observed. Diarylprolinol 84 (Figure 24.28) was developed with the aim of having a water-soluble catalyst that is easily recoverable in water. Catalyst 84 may be used... 

Dipolar addition to nitroalkenes provides a useful strategy for synthesis of various heterocycles. The [3+2] reaction of azomethine ylides and alkenes is one of the most useful methods for the preparation of pyrolines. Stereocontrolled synthesis of highly substituted proline esters via [3+2] cycloaddition between IV-methylated azomethine ylides and nitroalkenes has been reported.147 The stereochemistry of 1,3-dipolar cycloaddition of azomethine ylides derived from aromatic aldehydes and L-proline alkyl esters with various nitroalkenes has been reported. Cyclic and acyclic nitroalkenes add to the anti form of the ylide in a highly regioselective manner to give pyrrolizidine derivatives.148... 

In recent years, the importance of aliphatic nitro compounds has greatly increased, due to the discovery of new selective transformations. These topics are discussed in the following chapters Stereoselective Henry reaction (chapter 3.3), Asymmetric Micheal additions (chapter 4.4), use of nitroalkenes as heterodienes in tandem [4+2]/[3+2] cycloadditions (chapter 8) and radical denitration (chapter 7.2). These reactions discovered in recent years constitute important tools in organic synthesis. They are discussed in more detail than the conventional reactions such as the Nef reaction, reduction to amines, synthesis of nitro sugars, alkylation and acylation (chapter 5). Concerning aromatic nitro chemistry, the preparation of substituted aromatic compounds via the SNAr reaction and nucleophilic aromatic substitution of hydrogen (VNS) are discussed (chapter 9). Preparation of heterocycles such as indoles, are covered (chapter 10). 

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