Nitroalkenes activation

Scheme 6.5 Nitroalkene activation via double hydrogenbonding enhances electrophilicity at (J-position and facilitated Michael-type attack of the (hetero)aromatic nucleophile resulting in Friedel-Crafts adducts.

Secondary amines as Lewis bases in nitroalkene activation including asymmetric syntheses of heterocycles 13AfO904. 

The Diels-Alder reaction of nitroalkenes with Danishefsky s dienes is applied to synthesis of truncated carbocyclic analogues of a potent neuraminidase inhibitor 4-guanidino-NemAc en fsee Scheme 8.5. Carbocyclic analogs are found to retain interesting levels of antiviral activity comparable to those shovm by their oxygen-containing compounds in Scheme 8.5. 

Asymmetric Michael addition of chiral enolates to nitroalkenes provides a useful method for the preparation of biologically important compounds. The Michael addition of doubly deprotonated, optically active P-hydroxycarboxylates to nitroalkenes proceeds with high dias-tereoselectivity to give erythro-hydroxynitroesters (Eq. 4.58).76... 

Simple dienes are not reactive enough toward chiral l-(alkylsulfinyl)-2-nitroalkenes. To resolve this problem, the reaction of optically active l-(alkylsulfinyl)-2-nitroalkenes with simple... 

A few examples of cycloadditions between nitroalkenes and vinyl ethers without the use of Lewis acids have been reported (Eq. 8.105), in which additional activating electron-withdrawing groups are generally required.161... 

When a-tethered nitroalkenes bearing three or four methylene chains and ester-activated dipolarophiles react with vinyl ethers, spiro mode tandem cycloaddition takes place to give tricyclic spiro nitroso acetals in good yield and high diastereoselectivity (Scheme 8.46).184... 

The third cycloaddition substrate explored the feasibility of a vinyl nitro functionality as an activated dipolarophile (98, Scheme 1.9c). Preparation of nitroalkene oxidopyridinium betaine 98 began with silylenol ether 92, which was treated with methoxydioxolane in the presence of Lewis acid catalyst, TrC104, to afford keto dioxolane 93 in 58 % yield [47]. Ketone 93 then underwent a-nitration by treatment with /-BuONCL and KOt-Bu to provide nitro ketone 84 (91 %), which was then converted to the nitroalkene functionality via reduction under Luche conditions to... 

The reactions of 4-nitrobenzodifuroxan 242 with a series of common dienes, such as cyclopentadiene, cyclohexa-diene, isoprene, 2,3-dimethylbutadiene, and 1-acetoxybutadiene, with ethoxymethyleneacetylacetone were found to proceed very readily to afford stable cycloadducts, which are the result of highly stereoselective normal electron-demand (NED) Diels-Alder reactions. Due to the additional activation provided by the two adjacent furoxan rings, the nitroalkene double bond of compound 242 is also prone to undergo NED reactions with less reactive dienic structures, such as the enol form of ethoxymethyleneacetylacetone and the in situ generated 2-ethoxy-4-(2-furfur-yl)buta-l,3-diene <2004TL1037, 2005T8167>. 

The behavior of complexes of nitroalkenes (42) with LA toward conjugated dienes is yet another factor underlying the role of these complexes. Conjugated nitroalkenes (42) are considered as active dienophiles in classical Diels-Alder reactions (104, 105). On the contrary, in the presence of SnCl4, nitroalkenes (42) react with cyclopentadiene and 1,3-cyclohexadiene exclusively at one double bond (103). Therefore, it is highly probable that the 42 + 43 cycloaddition proceeds by a nonconcerted mechanism in the presence of LA (see Scheme 3.40). 

Besides rhodium catalysts, palladium complex also can catalyze the addition of aryltrialkoxysilanes to a,(3-unsaturated carbonyl compounds (ketones, aldehydes) and nitroalkenes (Scheme 60).146 The addition of equimolar amounts of SbCl3 and tetrabutylammonium fluoride (TBAF) was necessary for this reaction to proceed smoothly. The arylpalladium complex, generated by the transmetallation from a putative hypercoordinate silicon compound, was considered to be the catalytically active species. 

Chiral amino alcohols react with achiral nitroalkenes such as 1-nitrocyclohexene almost stereospecifically to give optically active products, e.g. equation 96305. 

In the course of their research about drugs with oncologic activity, Martinez and Iglesias75 examined the Diels-Alder reaction between 1-trirnethylsiIyloxy-l,3-butadiene (50) and nitroalkene 51 which afforded, after hydrolytic work-up, a mixture of two regioi-someric pairs of endo/exo isomers 52/53 and 54/55 in a ratio of 52/53/54/55 = 78 17 3 2 (equation 19). 

One or both of the disadvantages are Hkely to be overcome in due course. It is obvious that a clearer picture of the mechanism of the oxidation is mandatory before much progress can be made. Once it is understood how this very simple protein folds, in the presence of organic solvent, to form a chiral cavity or chiral surface that activates the peroxide and/or enone to accomplish the desired asymmetric oxidation then the reaction may be extended to other substrates, e.g. a, unsaturated esters, nitroalkenes, perhaps (under different conditions) electron-rich alkenes. 

When nitroalkenes were used as Michael acceptors, high yields and enantioselectivities of the desired Michael addition products were also obtained (Scheme 5.22). In these reactions, a well-defined chiral Ru amido complex (Figure 5.9) was an efficient catalyst. The mild reaction conditions and high reactivities and stereoselectivities allowed a large-scale reaction in the presence 1 mol% Ru catalyst. By using a chiral Pd(II) catalyst, an asymmetric allylic arylation was reported by Mikami and coworkers to give the cross-couphng product via the activation of both allylic C H and aryl C H bonds in moderate enantioselectivity (Scheme 5.23). ... 

Although phosphoric acids have found broad applicability for a wide range of asymmetric transformations, most reactions are limited to electrophilic activation of imines. Expanding the scope of phosphoric acid catalysis to other classes of electrophiles, Akiyama and Terada subsequently reported activation of nitroalkene [38] and carbonyl [39] electrophiles, respectively (Scheme 5.23). 

Tan also found that guanidine 21, acting as a base to activate the o [3], X [3] tautomers of diaryl phosphine oxides, catalyzes the asymmetric phospha-Michael reachon of aryl nitroalkenes (Scheme 5.42) [76]. He later employed 21 to realize highly enantioselective Michael additions of dithiomalonate and 3-keto thioesters with a range of acceptors, including maleimides, cyclic enones, furanone, and acyclic 1,4-dicarbonylbutenes [77]. 

A systematic study on enzymatic catalysis has revealed that isolated enzymes, from baker s yeast or old yellow enzyme (OYE) termed nitroalkene reductase, can efficiently catalyze the NADPH-linked reduction of nitroalkenes. Eor the OYE-catalyzed reduction of nitrocyclohexene, a catalytic mechanism was proposed in which the nitrocyclohexene is activated by nitro-oxygen hydrogen bonds to the enzymes His-191 and Asn-194 [167, 168]. Inspired by this study Schreiner et al. 

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