Nitro alkenes addition reactions

Tetraalkylammonium bromide was found to be a good catalyst for the conjugate addition of thiols to a,p-unsaturated nitriles, carboxylic esters, ketones, aldehydes, and nitro alkenes. The reactions proceeded rapidly and gave high yields of products (typically, 90%) (160). 

Similar workup conditions applied to the nitronate arising from 1,4-addition of unsaturated Grignard or Li reagents 80 (M = MgBr provided better yields) to P Ar or jS-hetero-Ar nitro alkenes 79 provided isoxazolines 82 in a practically one pot reaction sequence (Eq. 8, Table 7) [33]. 

Potential precursors to stereoselective INOC and ISOC reactions (e.g., 195 and 196, respectively) have been prepared via stereoselective conjugate additions of several allylic alcohols (e.g., 194,X = 0) and an allylic thiol (e.g., 194,X = S) to a chiral (E)-nitro alkene (e. g., 193) that was derived from (P)-2,3-isopropylidene... 

Attack on Unsaturated Carbon. The annual addition of phosphites to every variety of activated double bond continues. These include nitro-alkenes,9 a/S-unsaturated carboxylic acid derivatives,10 maleimides,11 fulvenes,12 and pyridinium salts.13 The reaction of diethyl phosphite with keten 0,N-, S,N, and Al,AT-acetals has been used to prepare the enamine phosphonates (19).14... 

Addition reactions of excited nitro groups to alkenes and alkines, both inter- and intramolecularly, have been reviewed previously ). 

A previous review has highlighted the following methods of ring synthesis intramolecular cyclization of oximes, nitro alkenes, and nitrones, and [4+2] cycloaddition reactions <1996CHEC-II(6)279>. In addition to that, this review includes the intramolecular cyclization of hydroxylamines, hydroxamates, hetero-Diels-Alder [4+2], 1,3-dipolar cycloaddition of nitrile oxides to alkenes, and [3+3] cycloaddition reactions. This review does not cover cycloaddition reactions of the [4+2] [3+2] and [4+2] [3+2] [3+2] types which primarily led to heterocycle-fused oxazine ring systems. 

It is interesting to note that the oxa-analogous Michael addition was reported for the first time in 1878 by Loydl et al. [19] in their work on the synthesis of artificial malic acid, which was five years ahead of the discovery of the actual Michael reaction described first by Komnenos [20], Claisen [21], and later Michael in 1887 [22] as one of the most important methods for C—C bond formation. In continuation of the early work on the oxa-Michael addition [23], the inter- and intramolecular additions of alkoxides to enantiopure Michael acceptors has been investigated, leading to the diastereo- and enantioselective synthesis of the corresponding Michael adducts [24]. The intramolecular reaction has often been used as a key step in natural product synthesis, for example as by Nicolaou et al. in the synthesis of Brevetoxin B in 1989 [25]. The addition of oxygen nucleophiles to nitro-alkenes was described by Barrett et al. [26], Kamimura et al. [27], and Brade and Vasella [28]. 

To enter the Barton-Zard condensation, a substrate must have essentially nitro-alkene character. This is the reason why the reaction with nitrobenzene fails and 1-nitronaphthalene also reacts slightly (94CC1019). An additional N02 group on the naphthalene ring substantially facilitates the transformation but the expected dipyrroles are not formed (95TL4381). Table 2 presents various substrates, the corresponding products and some other details of the Barton-Zard condensation. 

Reaction with -alkylthio nitro olefins. Nitro alkenes bearing an alkylthio or phenylsulfonyl group at the -position undergo addition-elimination reactions with organocopper/zinc reagents to provide functionalized (E)-nitro alkenes. 

The reaction is akin to the Ritter reaction, with activation achieved by nitration, rather than proton-ation, and the products accordingly retain the nitro group. Additions to 1-phenylcyclohexene (59%) and to franr-stilbene (72%) are stereospecific (trans) cfr-stilbene gives the expected tfireo product (39%) plus some erythro (6%). Reactions of nitrogen dioxide with alkenes are very complex and rarely use-ful. A recent mechanistic paper gives many key references. " Addition of NjOs is occasionally usefiil, as with dicyclopentadiene (Scheme 49). ... 

Nitro-stabilized anions also undergo additions to aldehydes, ketones, and electrophilic alkenes these reactions appear in Chapters 27 and 29. 

Multicomponent reactions (MCRs) were applied to the synthesis of substituted isoxazolines. For example, 64 was obtained by addition of nitro-alkene 60 and acrylate 61 to a solution of isonitrile 59 generated in situ by reaction of trimethylsilyl cyanide and isobutene oxide in the presence of Pd(CN)2 <05OL3179>. This cascade MCR is believed to occur through [1+4] cycloaddition of 59 with 60, subsequent fragmentation of 62 and 1,3-DC of nitrile oxide 63 with 61. Under microwave irradiation, reaction times could be reduced from several hours to 15 min, with comparable yields. 

A relatively rare example of the creation of chiral quaternary carbons has been uncovered in Michael addition-elimination reactions between lactone enolates [e.g. (444)] and a chiral nitro-alkene (445) ... 

A in the equation represents a substituted aldehyde. An electron withdrawing group can activate the double bond and its the electron-withdrawing capability is related to the produced electronegativity, which are usually believed that nitro is the strongest followed by sulfonic acid group [20]. The double bond is between the substituted a, P carbons, a, P-Unsaturated carboxylic acids, carboxylic acid esters, nitriles, acids, ketones, sulfones, aldehydes, ethers, olefins and heterocyclic alkene can all react with nitroalkane via addition reactions to form the corresponding nitro-derivatives. 

Importantly, prolinamide catalysts (Figure 6.3) work well in Michael addition reactions using nitro-olefins as acceptors. iV-Tritylprolinamide 33 and aminonaphthyridine-derived ProNap 34 served as organocatalysts in asymmetric Michael additions of aldehydes and cyclohexanone to nitro-alkenes. Proline-functionalised C3-symmetric 1,3,5-triallq lbenzene 35 was screened in the reaction of cyclohexanone to nitrostyrene to afford the Michael adducts in good yields and diastereoselectivity but low enantioselectivity. 

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