Nitroalkenes nitroalkanes

METAL NITROPHENOXIDES, NITROACYL HALIDES NITROALKANES, NITROALKENES... 

Cycloaddition of Nitroalkanes/Nitroalkenes to Unsaturated Compounds. 9.2 Inter- and Intramolecular Cyclization of Oximes... 

N—NITRO COMPOUNDS C-NITRO COMPOUNDS NITROACYL HALIDES NITROALKANES NITROALKENES... 

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 Michael addidon of nitroalkanes to nitroalkenes is catalyzed by triethylamine to give 1,3-dirutro compounds fEq. 4.45. In some cases, the intramolecular displacement of thenitro group takes place to give cyclic nitronates fEq. 4.46. ... 

In d sumldf way, a-nitroselenides are prepared via the reacdon of nitronates with phenylse-lenyl bromide, which gives a new synthedc method of 1-nitroalkenes from nitroalkanes The sequence of ct-selenadon, nitro-aldol reacdon, and oxidadon provides a nsefid method for the preparadon of nitroalkenes with a hydroxymethyl group fEq 5 81 ... 

The reacdon of nitroalkenes or nitroalkanes v/ithTCH and Me-SiN-, gives ct-azido fiincdon-alized hydroxamoyl chlciides, which act as precursors of nitnle oxides fEq. 6.34. " ... 

All of these reacdons ptoceed in a similar pathway which involves the Michael type addidons of enamines to nitroalkenes or addidon of nitroalkanes to Imines and cyclizadon. This process has been achieved by solid-phase variadon fScheme 10.2. ... 

The direct aziridinadon of nitroalkanes has been repotted for the first dme. Treatment of nitroalkene with an excess of CaO and NsONHCO-.Et fNs =4-nitroben2enesulfonyl gives the ct-nitroaziridine in good yields fEq. 10.70. ° The reaction proceeds via aza-Michael reaction followed by a ring closure. 

Scheme 2.23 provides some examples of conjugate addition reactions. Entry 1 illustrates the tendency for reaction to proceed through the more stable enolate. Entries 2 to 5 are typical examples of addition of doubly stabilized enolates to electrophilic alkenes. Entries 6 to 8 are cases of addition of nitroalkanes. Nitroalkanes are comparable in acidity to (i-ketocslcrs (see Table 1.1) and are often excellent nucleophiles for conjugate addition. Note that in Entry 8 fluoride ion is used as the base. Entry 9 is a case of adding a zinc enolate (Reformatsky reagent) to a nitroalkene. Entry 10 shows an enamine as the carbon nucleophile. All of these reactions were done under equilibrating conditions. 

The 3-nitro alcohols are generally obtained in good yield by the reaction of aldehydes with nitroalkanes in the presence of a catalytic amount of base. When aryl aldehydes are used, the (3-nitro alcohols formed may undergo elimination of water to give aryl nitroalkenes. Such side reactions are not always disadvantageous, for nitroalkenes are sometimes the ultimate target for the Henry reaction. The choice of reaction conditions is important to stop the reaction at the stage of 3-nitro alcohols in aromatic cases. 

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... 

The reduction of nitroalkenes with ZnBH4 in 1,2-dimethoxyethane (DME) gives the corresponding oximes or nitroalkanes depending on the structure of nitroalkenes. a-Substituted nitroalkenes are reduced to the oximes, whereas those having no a-substituents afford the... 

Very selective reduction of nitroalkenes into the corresponding nitroalkanes is achieved using NaCNBH3 in the presence of the zeolite H-ZSM 5 in methanol (Eq. 3.48).78... 

The addition of alkoxides to 2-nitro-l-phenylthio-l-alkenes affords P-nitro-aldehyde acetals.276 The reaction of the same nitroalkenes with amines gives nitroenamines.270 They are important intermediates for organic synthesis and are generally prepared by the reaction of nitroalkanes with triethylorthoformate in the presence of alcohols or secondary amines.2"1 0 The methods of Eqs. 4.20 and 4.21 have some merits over the conventional methods, for variously substituted (3-nitro-aldehydes acetals or nitroenamines are readily prepared by these methods. 

The 1,4-addition of RMgX or RLi to nitroalkenes produces nitronate intermediates, which are converted into nitroalkanes, nitrile oxides (oxime chlorides), or carboxylic acids, depending on the conditions of hydrolysis (Scheme 4.14).94... 

The conversion of primary or secondary nitro compounds into aldehydes or ketones is normally accomplished by use of the Nef reaction, which is one of the most important transformations of nitro compounds. Various methods have been introduced forthis transformation (1) treatment of nitronates with acid, (2) oxidation of nitronates, and (3) reduction of nitroalkenes. Although a comprehensive review is available,3 important procedures and improved methods published after this review are presented in this chapter. The Nef reaction after the nitro-aldol (Henry reaction), Michael addition, or Diels-Alder reaction using nitroalkanes or nitroalkenes has been used extensively in organic synthesis of various substrates, including complicated natural products. Some of them are presented in this chapter other examples are presented in the chapters discussing the Henry reaction (Chapter 3), Michael addition (Chapter 4), and Diels-Alder reaction (Chapter 8). 

The reaction of nitroalkenes or nitroalkanes with TiCl4 and Me3SiN3 gives a-azido functionalized hydroxamoyl chlorides, which act as precursors of nitrile oxides (Eq. 6.34).59... 

The conversion of nitroalkanes to ketoximes can be achieved by the reduction with Zn in acetic acid,112 or Fe in acetic acid.113 Nitroalkenes are direcdy reduced into saturated ketoximes by these reagents, which are precursors for ketones (see Section 6.1.4 Nef reaction). Reduction of 3-O-ace-ty lated sugar 1 -nitro-1 -alkenes with Zn in acetic acid gives the corresponding 2,3-unsaturated sugar oximes in high yield, which is a versatile route to 2,3-unsaturated sugar derivatives (Eq. 6.58).114... 

The C2-symmetric bifunctional tridentate bis(thiazoline) 222 has been shown to promote the zinc(II)-catalyzed asymmetric Michael addition of nitroalkanes to nitroalkenes in high enantioselectivity <06JA7418>. The corresponding bis(oxazoline) ligand provides comparable enantioselectivity but higher product yield. The same bis(thiazoline) ligand has also been evaluated in the enantioselective Friedel-Crafts alkylation of indoles, but the enantioselectivity is moderate <06OL2115>. 

The condensation reaction of neat carbonyl compounds with nitroalkanes to afford nitroalkenes, Henry reaction, also proceeds rapidly via this MW approach in the presence of only catalytic amounts of ammonium acetate, thus avoiding the use of a large excess of polluting nitrohydrocarbons normally employed (Scheme 6.22) [72],... 

The cycloaddition, reduction and oxidation reactions emanating from a,/J-unsatu-rated nitroalkenes provide easy access to a vast array of functionalities that include nitroalkanes, N-substituted hydroxylamines, amines, ketones, oximes, and a-substi-tuted oximes and ketones [73-75], Consequently, there are numerous possibilities of using these in situ generated nitroalkenes for the preparation of valuable building blocks and synthetic precursors. 

Silylation of Products of Conjugated Addition of Nucleophiles to a-Nitroolefins Nitroalkane anions can be generated not only by deprotonation of nitroalkanes (various modifications of these process were considered above) but also by the conjugated addition of nucleophiles 56 to a-nitroalkenes (42) (Scheme 3.56, Table 3.2). 

The addition of tetrabutylammonium acetate appeared to be very useful for desilylation of intermediates A (see Scheme 3.232). An efficient procedure was developed for the oxidation of nitroalkanes to nitroalkenes with the use of this reagent (250) (Scheme 3.234). 

This process can be used with advantage for the preparation of conjugated nitroalkenes from nitroalkanes. It is of interest because the majority of known synthetic methods for generating nitroalkenes, the skeletons of target molecules, are generally assembled from simpler molecules (104). 

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