Nitroalkenes, formation

Scheme 6.104 Key intermediates of the proposed catalytic cycle for the 100-catalyzed Michael addition of a,a-disubstituted aldehydes to aliphatic and aromatic nitroalkenes Formation of imine (A) and F-enamine (B), double hydrogen-bonding activation of the nitroalkene and nucleophilic enamine attack (C), zwitterionic structure (D), product-forming proton transfer, and hydrolysis.

Concerning the reaction mechanism, the transformation of an aldehyde into a nitroalkene can occur via two different pathways the first involves nitroalcohol formation through a traditional Henry reaction, which is then followed by water elimination to form the double bond the second proceeds through an imine intermediate rather than the nitroalcohol. The authors predicted that nitroalkene formation goes through an imine intermediate (Scheme 3.9) rather than the nitroalcohol as they did not observe nitroalcohol formation at any point in the reaction. In addition, when the nitroalcohol is placed in the presence of swollen capsules, no nitroalkene formation is observed this inability to... 

Nadtochiy, S.M., Baker, P.R., Freeman, B.A., and Brookes, P.S. 2009. Mitochondrial nitroalkene formation and nuld uncouphng in ischaemic preconditioning Implications for cardioprotection. CaMovasc R 82, 333—340. 

Beyond secondary amines, various chiral Brpnsted acid and hydrogen-bonding donor catalysts, supported primary amines were also demonstrated to be suitable catalysts to implement metal/organic binary catalytic systems. In 2006, McQuade et al. reported a cascade three-component reaction by combining encapsulated amine and nickel catalysts with high reactivity and chemoselectivity [81]. The reaction proceeded through an encapsulated amine-promoted nitroalkene formation via iminium ion intermediate followed by a nickel complex-promoted chemoselective Michael addition of dimethyl malonate to the newly generated nitroalkene (Scheme 9.76). 

Formic acid is a good reducing agent in the presence of Pd on carbon as a catalyst. Aromatic nitro compounds are reduced to aniline with formic acid[100]. Selective reduction of one nitro group in 2,4-dinitrotoluene (112) with triethylammonium formate is possible[101]. o-Nitroacetophenone (113) is first reduced to o-aminoacetophenone, then to o-ethylaniline when an excess of formate is used[102]. Ammonium and potassium formate are also used for the reduction of aliphatic and aromatic nitro compounds. Pd on carbon is a good catalyst[103,104]. NaBH4 is also used for the Pd-catalyzed reduction of nitro compounds 105]. However, the ,/)-unsaturated nitroalkene 114 is partially reduced to the oxime 115 with ammonium formate[106]... 

The mechanism is presumed to involve a pathway related to those proposed for other base-catalyzed reactions of isocyanoacetates with Michael acceptors. Thus base-induced formation of enolate 9 is followed by Michael addition to the nitroalkene and cyclization of nitronate 10 to furnish 11 after protonation. Loss of nitrous acid and aromatization affords pyrrole ester 12. 

Formation of C-C Bonds by Addition to Olefinic Double Bonds Enimines, Nitroalkenes, 4,5-Dihydrooxazoles, a,/MJnsaturated Sulfones, Sulfoxides and Sulfoximines... 

Dipolar [3 + 2] cycloadditions are one of the most important reactions for the formation of five-membered rings [68]. The 1,3-dipolar cycloaddition reaction is frequently utihzed to obtain highly substituted pyrroHdines starting from imines and alkenes. Imines 98, obtained from a-amino esters and nitroalkenes 99, are mixed together in an open vessel microwave reactor to undergo 1,3-dipolar cycloaddition to produce highly substituted nitroprolines esters 101 (Scheme 35) [69]. Imines derived from a-aminoesters are thermally isomerized by microwave irradiation to azomethine yhdes 100,... 

The base-catalyzed reaction of dialkyl phosphite with nitroalkenes results in the formation of alkenyl phosphonates (Eq. 4.33).39... 

Interesting intramolecular cyclization of 1-nitroalkyl radicals generated by one-electron oxidation of aci-nitro anions with CAN is reported. As shown in Eq. 5.44, stereoselective formation of 3,4-functionalized tetrahydrofurans is observed.62 l-Nitro-6-heptenyl radicals generated by one electron oxidation of aci-nitroanions with CAN afford 2,3,4-trisubstituted tetrahydropyrans.63 The requisite nitro compounds are prepared by the Michael addition of 3-buten-l-al to nitroalkenes. 

DBU is most widely employed as the base in the Barton-Zard reaction. Stronger nonionic bases such as P(MeNCH2CH2)3N and the phosphazene base (supplied by Fluka) are more effective to induce pyrrole formation in the reaction of nitroalkenes with isocyano esters than DBU.39 Sterically hindered nitroalkenes are converted into the corresponding pyrroles using these bases, as shown in Eq. 10.35,39b but DBU is not effective in this transformation. 

The formation of nitrocyclobutanes (44) is attributed to the contribution of the structure B" to the reactivity of stabilized zwitterionic intermediate B. The contribution of C-alkylation decreases due to steric hindrance caused by the presence of substituents at the a-position of the initial nitroalkene (42). 

The reactions of nitroalkenes (42) with various enols (43b) (vinyl ethers, silyl, and acyl enolates, ketene acetals) have been studied in most detail (110, 111, 125—154). As a mle, these reactions proceed smoothly to give the corresponding nitronates (35f) in yields from high to moderate. As in the reactions with enamines, the formation of compounds (44b) is attributed to the ambident character of the anionic centers in zwitterionic intermediates analogous to those shown in Scheme 3.43. 

In spite of the success of asymmetric iridium catalysts for the direct hydrogenation of alkenes, there has been very limited research into the use of alternative hydrogen donors. Carreira and coworkers have reported an enantioselective reduction of nitroalkenes in water using formic acid and the iridium aqua complex 69 [66]. For example, the reduction of nitroalkene 70 led to the formation of the product 71 in good yield and enantioselectivity (Scheme 17). The use of other aryl substrates afforded similar levels of enantioselectivity. 

The asymmetric tandem cycloaddition of the chiral carbohydrate nitroalkene (35) with ethyl vinyl ether involves the initial formation of the nitronate (36) which reacts exclusively with electron-withdrawing alkenes by 3 -I- 2-cycloaddition to yield chiral bicycles (37) and (38) (Scheme 12). ... 

Some 1,3-dinitroalkanes (145) have been synthesized from the reaction of nitroalkanes with a-nitroalkenes (144) generated in situ from the decomposition of Mannich bases (143) derived from primary nitroalkanes. Reported yields for these reactions are low and the formation of by-products limits the feasibility of the method. 

Mobashery and co-workers also reported the synthesis and inhibitory apph-cation of 2 -N02 derivatives of neamine and kanamycin (Scheme 4.28). Using the metal-chelating method, the 2 -NH2 was selectively unmasked and then oxidized into 2 -N02, which will increase the acidity of 2 -H. Upon phosphorylation at the 3 -0H, elimination of phosphate will lead to the formation of a nitroalkene intermediate, 198, that can function as a Michael acceptor and... 

Figure 8. Formation of a carbohydrate nitrocyclopropane from a nitroalkenic sugar via a pyrazoline.

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