1-Nitroalkenes

Nitroalkenes are widely used in the eatalytie AFC alkylation of electron-rich aromatic rings such as indoles, pyrroles, electron-rich furans, and phenols. The literature up to 2009 dealing with catalytic AFC alkylation of aromatic compounds with nitroalkenes has been reviewed. In this section, only very recent progress on the development on catalytic AFC alkylation of nitroalkenes will be diseussed. 

Carmona, Rodriguez, and co-workers disclosed an unexpeeted catalytic pathway for the AFC reaction between trans-p-nitrostyrenes and iV-methyl-2-methylindole catalyzed by the half-sandwich aqua complex 151. Metal-nitroalkene, metal-ad-nitro, and free-aci-nitro intermediates have been 

In 2009, You and co-workers developed a chiral phosphoric acid-catalyzed AFC reaction of nitroalkenes with 4,7-dihydroindoles. With slow addition of nitroalkene by syringe pump, the reaction proceeded to completion in 2 hours with only 0.5 mol% catalyst. The corresponding adducts were obtained in excellent yields (93-98%) with up to 97% ee. 2-Substituted indole derivatives were obtained by oxidation of AFC adducts with 2 equivalents of j3-benzoquinone without losing any ee value. You and co-workers 

Sohtome, Nagasawa, and eo-workers developed a new strategy for asymmetric organocatalysis by introducing conformationally flexible catalysts.  

Conjugated nitroalkenes are isomerized to allylic nitro compounds under basic conditions. Reactions of a,P-unsaturated nitro compounds with aldehydes under basic conditions lead directly to y,8-unsaturated P-nitro alcohols (Eq. 3.24). 3 This reaction is very useful for preparing allylic nitro compounds. 

Dehydration of P-nitro alcohols provides an important method for the preparation of nitroalkenes. Because lower nitroalkenes such as nitroethylene, 1-nitro-1-propene, and 2-nitro-l-propene tend to polymerize, they must be prepared carefully and used immediately after preparation. Dehydration with phthalic anhydride is the most reliable method for such lower nitroalkenes.42,43 Such lower nitroalkenes have been used as important reagents for Michael acceptors or dienophiles in the Diels-Alder reaction, which will be 

Dehydration of (3-nitro alcohols using DCC gives a mixture of E/Z nitroalkenes 48 The pure (E)-isomers are obtained on treatment with catalytic amounts of triethylamine or polymer-bound triphenylphosphine (TPP) (Eq. 3.28).51 When (Z) nitroalkenes are desired, the addition of PhSeNa to the E/Z mixture and protonation at -78 °C followed by oxidation with H202 gives (Z)-nitroalkenes (Eq. 3.29).52 

A1203 can be used both as a base for the Henry reaction and as a dehydrating agent. Thus, nitroalkenes are simply prepared by mixing of aldehydes and nitroalkanes with A1203 and subsequent warming at 40 °C (Eq. 3.30).53 

In general, base-catalyzed reactions of aromatic aldehydes with nitroalkanes give nitroalkenes directly (Knoevenagel reaction).54 The reaction is very simple heating a mixture of aromatic aldehydes, nitroalkanes, and amines in benzene or toluene for several hours using a Dean-Stark water separator gives the desired nitroalkenes in good yield, as shown in Eqs. 3.31-3.34.54-58 

Dehydration of fi-nitro alcohols is generaUy carried out by the foUowing reagents, phthahc anhydnde, CH-,SO-,Cl-Et-,N, dicyclohexylcarbodhmide iDCCi, Ac-,0-AcONa, Ph.P-CCH, andTFAA-EtiN, as exemplified in Eqs. 3.26 and 3.27 .  

Instead of using the Dean-Stark apparanis, the reacdon can be carried out at reflux using MeNH-vCl/AcOK/MeOH with HCfOMe, as a water scavenger, A wide variety of nitroalkenes can be prepared in good yields by this method fEq, 3,35,  

Despite of the fact that Baylis and Hillman reported the synthesis of a-hydr-oxyethylated nitroethylene through the reaction between nitroethylene and acetaldehyde in the presence of DABCO, nitroalkenes employed as activated olefins in MBH reaction have not received much attention until recently. Prompted by the fact that nitroalkenes have shown superior Michael acceptor abilities, and that the first step in the MBH reaction is the Michael-type addition of the catalyst to substrate, Namboothiri et al. have published a series of papers on nitroalkenes involved the MBH reaction. The MBH reactions between nitroalkenes and various electrophiles such as formaldehyde, activated carbonyl compounds, imines, alkenes and azodicarboxylates in the presence 

I 7 Copper-catalyzed Enantioselective Conjugate Addition Reactions of Organozinc Reagents 

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Some electron deficient dienophiles are quinones, maleic ahydride, nitroalkenes, a,p-unsaturated ketones, esters and nitriles. 

Internal nitroalkenes can be reduced to the corresponding ketox-imes by SnCla. The second method is a modification of the first, also allowing terminal nitroalkenes (such as nitrostyrenes) to be reduced to aldoximes. The oximes, in turn, can either be reduced to the corresponding amines, or cleaved to form the carbonyl compound. 

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 Barton-Zard reaction refers to the base-induced reaction of nitroalkenes 1 with alkyl a-isocyanoacetates 2 to afford pyrroles 3. Solvents used are THF or alcohols (or mixtures) and the reaction often proceeds at room temperature. 

The Barton-Zard (BZ) pyrrole synthesis is similar both to the van Leusen pyrrole synthesis that uses Michael acceptors and TosMlC (Section 6.7) and the Montforts pyrrole synthesis using a,P-unsaturated sulfones and alkyl a-isocyanoacetates." An alternative to the use of the reactive nitroalkenes 1 is their in situ generation from P-acetoxy nitroalkanes, which are readily prepared via the Henry reaction between an aldehyde and a nitroalkane followed by acetylation. Examples are shown later. 

In 1985, in the course of their interest in nitroalkane chemistry, Barton and Zard reported the base-catalyzed reaction of nitroalkenes with a-isocyanoacetates leading to pyrrole esters having an ideal substitution pattern for the synthesis of porphyrins and bile... 

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. 

The final class of reactions to be considered will be the [4 + 2]-cycloaddition reaction of nitroalkenes with alkenes which in principle can be considered as an inverse electron-demand hetero-Diels-Alder reaction. Domingo et al. have studied the influence of reactant polarity on the reaction course of this type of reactions using DFT calculation in order to understand the regio- and stereoselectivity for the reaction, and the role of Lewis acid catalysis [29]. The reaction of e.g. ni-troethene 15 with an electron-rich alkene 16 can take place in four different ways and the four different transition-state structures are depicted in Fig. 8.16. 

Hie stereodiemical trendi disaissed above carbonyl compounds otlier Micliael acceptor rated pbospbane oxides display sim dar bebavi-nitroalkene class of Micliael acceptors is show [28]. Hie best results were tlius obtained for were niucli less selective, wbicli severely restri... 

Cychc nitroalkenes are prepared from cychc ketones via nitradon of vinylstarmanes v/ith tetranitrmnethane in DMSO, as shown in Eq 2 36, where DMSO is a cridcal choice of solvent for replacing dn by nitre at the unsaturated carbon The conversion of ketones to vinylstarmanes... 

The synthesis of cyclic nitroalkenes via nitradon of cyclo ilkenes is sttmmarized in Table 3 3 Acyclic nitro ilkenes are more readily prepared via the Henry reacdon than by nitradon of ilkenes fsee Secdon 3 3 1 ... 

OxiddQon of oximes to rutro compounds with w-CPBA has been applied to the synthesis of dialkyl l-nitroalkanephosphonates fEq 2 63, which are useful reagents for d carbonyl compounds to nitroalkenes... 

Allylic nitro compounds are obtained by the reacdon of cyclic ketones with nitromethane in the presence of 1,2-diaminoethane fl mol% as catalyst. Because exa-cyclic nitroalkenes are rearranged to the fi)iifo-cyclic fi,Y-nitroalkenes, allylic nitro compounds are selecdvely produced fEq. 3.21. ... 

The Michael adclidon of a nitrogen-centered nucleophile to nitroalkenes affords compounds that may serve as precursors of vicinal chamines, since the nitro group can be reduced to an amino function by reduction The very convenient method for the preparation of 1,2-chamines is developed by the adchdon of O-ethyihydroxylamines to nitroalkenes followed by redncdon with H-, in the presence of PckC fEq 4 24 ... 

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