Aliphatic-substituted nitroalkenes

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. 

Michael additions are among the most important organocatalytic transformations.The ability of prolinol silyl ethers to form enamines, diena-mines, trienamines or iminium ions makes them appealing in a number of chemical transformations based on addition of a nucleophile to an a,p-unsaturated carbonyl compound or other Michael acceptor. The first example of Michael addition catalysed by a prolinol silyl ether was published by Hayashi and coworkers. Aliphatic aldehydes added to a range of aryl-substituted nitroalkenes. Prolinol silyl ether Cla presumably formed chiral enamines with aldehydes. The F-anh-enamine was formed and it reacted with nitroalkene via an acyclic synclinal transition state, originally proposed... 

Du and coworkers have developed a stereoselective direct Michael addition of nitroalkanes to nitroalkenes catalyzed by quinine-derived dimeric squaramide 21 [93]. This transformation provided facile access to 1,3-dinitro compounds in high diastereo- and enantioselectivities starting from aryl-substituted nitroalkenes (Scheme 10.18). However, the use of an aliphatic nitroalkene as Michael acceptor resulted in a low yield and diminished enantioselectivity. While nitroethane and 1-nitropropane are excellent substrates, branched 2-nitropropane did not undergo the Michael addition reaction. The authors also noted that slightly reduced dias-... 

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). 

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... 

Later, the same group succeeded in achieving a cascade Michael/nitro-Mannich/ acetalization reaction by the combination of covalent enamine catalysis and noncovalent bifunctional base/Br0nsted acid catalysis [32]. The fuUy substituted piperidines with diverse substitution patterns were prepared efficiently starting from simple aliphatic aldehydes, Ts-protected imines, and trani -P-nitro alkenes (Scheme 9.36). This finding effectively incorporated prolinol silyl ether-catalyzed Michael addition of aldehyde 65 to nitroalkene 75 and valine-derived bifunctional thiourea-mediated nitro-Mannich reaction of y-nitro aldehyde 106 to imine 105 in the cascade process, providing a complementary contribution to the well-known single catalyst-promoted triple cascade reactions and two catalyst-promoted reaction cascades. 

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