Aromatic-substituted nitroalkenes

F-C reactions 1043,1045 aromatic-substituted nitroalkenes 254 aromatic systems 1043... 

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). 

The nucleophilic aromatic substitution of 6-nitropiperonal with [ F]K(Kryptofix 2.2.2)F yielded 6-[ F]fluoropiperonal that was condensed with nitromethane. Reduction and subsequent hydrolysis of the intermediate nitroalkene provided the target compound 6-[ F]FDA. In comparison to more direct approaches which utilize electrophilic aromatic substitution with positive polarized p F]fluo-rine [140-142], this type of preparation is characterized by high specific radioactivity, which is requested for human PET studies with vasopressor compounds, like 6-FDA [139,143]. 

S. Oxindole Derivatives. Most recently, Curti et al. [140] disclosed the first example of a direct, organocatalytic asymmetric vinylogous Michael addition of 3-alkylidene oxindole to nitroalkenes. Bifunctional cinchona alkaloid/thiourea catalyst 69 could effectively promote the reaction, solely aHbrding the 7-substituted 3-alkylidene oxindoles 146 with excellent regio-, diastereo-, and enantioselectivities (Scheme 5.71). Importantly, both aromatic and aliphatic substituted nitroalkenes were applicable for such a reaction. 

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... 

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). 

Bicyclic nitroso acetals were able to be synthesised by employing ethyl vinyl ether (dienophile), styrene (dipolarophile) and the previously discussed resin-bound ni-troalkenes in a one-pot tandem [4+2]/[3+2]. As illustrated in Scheme 7.30, several aromatic and aliphatic substituents could be introduced to the bicyclic scaffold. Reductive cleavage of the cycloadducts with lithium aluminium hydride (LLAIH4) gave rise to the 3a-methyl alcohol substituted nitroso acetals in moderate overall yields. All these examples demonstrate that resin-bound nitroalkenes can be readily synthesised by microwave synthesis and thereafter can be used as starting materials, in a variety of high pressure-promoted cycloadditions. 

The relative Michael-acceptor abilities of a variety of substituted aromatic and aliphatic nitroalkenes have been elucidated by computational methods. Several global and local reactivity indices were evaluated with the incorporation of the natural charge obtained from natural bond orbital (NBO) analysis. Natural charges at the carbon atom to the NO2 group and the condensed Fukui functions derived by this method were found to be consistent with the reactivity.187... 

A highly enantioselective Michael addition of 1,3-dicarbonyl compounds to nitroalkenes has been reported that employs a newly developed Ni(II)-(bis)diamine-based catalyst (174). The reaction scope includes substituted and unsubstituted malonates, /3-keto esters, and nitroalkenes bearing aromatic and aliphatic residues.202... 

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. 

The quinine derived thiourea 12 was found to be the most efficient catalyst, in terms of conversion and enantioselectivity, in the Michael-Michael cascade process between tra y-3-(2-mercaptoaryl)-2-propenoic acid esters and /ra 5-nitroalkenes [39]. The thiochromanes, containing three new stereocenters, were obtained with excellent enantio- and diastereoselectivity irrespective of the electronic namre and substitution pattern of the aromatic ring in the nitroalkene and in the thiol. Although the first sulfa-Michael step of the process was poorly enantioselective, it was also reversible, so that the enantiomeric mixture of the adducts underwent an efficient dynamic kinetic resolution due to a retro-Michael-Michael-Michael sequence (Scheme 14.10). 

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