Nitroalkenes heteroaromatic

Rovis and co-workers have also extended the intermolecular Stetter reaction to inclnde nitroaUcenes as the electrophilic component. Fluorinated triazolinm precatalyst 155 was effective in catalysing the reaction of a variety of heteroaromatic aldehydes 153 with nitroalkenes 154 to generate P-nitroketones in excellent yields and enantioselectivities. The authors propose that stereoelectronically induced conformational effects on the catalyst skeleton are key to the high selectivities observed with flnorinated catalyst 155 (Scheme 12.33) [69],... 

Heteroaromatic substituted nitroalkenes also participate in this high-pressure reaction sequence. For example, the reaction of 198a-c with 197 and methyl acrylate afforded diastereomeric mixtures of 199a-c in 53-74% yields (Scheme 34) (01EJOC553). In contrast, 198a reacted with 197 and A-phenyl maleimide to provide 200 as a single diastereomer. 

Barluenga et al. have extended the scope of the method by reaction with heteroaromatic and aliphatic nitroalkenes and the use of 2-aminobutadienes with a protected hydroxymethyl substituent at C-4 synthesized by the... 

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). 

Later in 2011, the Rovis group achieved excellent enantioselectivity and reactivity in the Stetter reaction of enals with nitroalkenes (up to 98% yield and 98% ee). Enals are reasoned to be a suitable alternative to heteroaromatic aldehydes due to their electronic similarity to aryl aldehydes but sterically less demanding and lacking a proximal Lewis base. The reaction rate and efficiency are profoundly impacted by the presence of catechol. Yield was improved... 

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

In 2004, Ricci and coworkers reported a sustainable Friedel-Crafts adulation of nitroalkenes with various aromatic and heteroaromatic substrates utilising 10 mol% of thiourea 8 under solvent-free reaction conditions. When applied to indoles, this method provides excellent yields and high selectivities (Scheme 19.8). Additionally, allqrlation at the difficult 2-position of the 3-methylindole was accomplished in a solvent-free reaction with the assistance of microwave irradiation (MW). 

A range of aromatic and heteroaromatic nitroalkenes reacted smoothly with ethyl as well as methyl hromomalonates to give the corresponding cyclopropanes in high yields and enantioselectivities (85-99% ee). To explain the stereoselectivity of the process, the authors have proposed that the bromo-malonate was activated by the nickel catalyst through a bidentate fashion. Then, the bromomalonate anion attacked the Si face of the double bond of the nitroalkene, as shown in the transition state depicted in Scheme 2.43. 

Nitroalkenes were the addition partners for these reactions, and a number of nitrostyrenes bearing a range of electron-donating and electron-withdrawing groups as weU as several heteroaromatic substrates were successfully transformed into phosphonylpyrazoles. 

Ricci et al studied a series of thiourea catalysts for the Friedel-Crafts alkylation of aromatic and heteroaromatic compounds with nitroalkenes. They have succeeded in developing the Friedel-Crafts alkylation of indoles with nitroalkenes for the first time by means of a novel thiourea catalyst (13) (Scheme 2.48) [101]. The authors proposed the bifunctional nature of the thiourea catalyst, where thiourea activates the nitro group and at the same time the free alcoholic function interacts with the indole proton through a weak hydrogen bond, directing the attack of the incoming nucleophile on the Si face of the nitroalkene (Figure 2.18). 

Aromatic and heteroaromatic nitroalkenes 353 gave the nitroalkanes 354 [521] in excellent yields. From oximes [522] chiral amines were obtained [308], whereas hydra-zones were hydrolyzed to the corresponding carbonyl compounds [523]. 

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