Nitroalkenes from alkenes

Nitric acidlacetic anhydride Nitrations with acetyl nitrate 2-Acetoxynitro compounds and 3-nitroalkenes from alkenes... 

There are reviews dealing with conjugated nitroalkenes in organic synthesis, " nitroenamines, the oxyalkylation of carbonyl compounds with conjugated nitroalkenes and the use of conjugated nitroalkenes in the synthesis of heterocyclic compounds. In this section mainly the preparation of nitroalkenes starting from alkenes is described. 

The introducdon of heterodienes has extended the synthedc versatility of cyclokldmon teac-dons in organic synthesis. " Denmark and coworkers have developed the use of rutroalkenes as dienes in [4+2 cycloaddidon. Nitroalkenes react v/ith simple alkenes in the presence of SnCi, as a promoter. For example, the reacdon of tutrocyclohexene v/ith cyclopentene gives three products. The major product is ruiri-isoraer, which arises from an fixn approach of cyclopentene toward tutrocyclohexene fsee Eq. 8.94. ... 

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,... 

A very attractive method for the preparation of nitroalkenes, which is based on the reaction with NO, has been reported. Treatment of alkenes at ambient pressure of nitrogen monoxide (NO) at room temperature gives the corresponding nitroalkenes in fairly good yields along with P-nitroalcohols in a ratio of about 8 to 2. The nitroalcohol by-products are converted into the desired nitroalkenes by dehydration with acidic alumina in high total yield. This simple and convenient nitration procedure is applied successfully to the preparation of nitroalkenes derived from various terminal alkenes or styrenes (Eq. 2.27).53 This process is modified by the use of HY-zeolites instead of alumina. The lack of corrosiveness and the ability to regenerate and reuse the catalyst make this an attractive system (Eq. 2.28).54... 

The synthetic applications of this reagent to the synthesis of nitroalkenes have been known since the 1960s.60 Nitration of alkenes with nitryl iodide, generated in situ from iodine and silver nitrite, is convenient for the synthesis of P-nitrostyrenes with various functional groups.61 This method is applied to the synthesis of ortho-methoxylated phenylisopropylamines, which are potent serotonine agonists (Eq. 2.31).62... 

Alkyl and silyl nitronates are, in principle, /V-alkoxy and /V-silyloxynitrones, and they can react with alkenes in 1,3-dipolar cycloadditions to form /V-alkoxy- or /V-silyloxyisoxaz.olidine (see Scheme 8.25). The alkoxy and silyloxy groups can be eliminated from the adduct on heating or by acid treatment to form 2-isoxazolines. It should be noticed that isoxazolines are also obtained by the reaction of nitrile oxides with alkenes thus, nitronates can be considered as synthetic equivalents of nitrile oxides. Since the pioneering work by Torssell et al. on the development of silyl nitronates, this type of reaction has become a useful synthetic tool. Recent development for generation of cyclic nitronates by hetero Diels-Alder reactions of nitroalkenes is discussed in Section 8.3. 

Dipolar addition to nitroalkenes provides a useful strategy for synthesis of various heterocycles. The [3+2] reaction of azomethine ylides and alkenes is one of the most useful methods for the preparation of pyrolines. Stereocontrolled synthesis of highly substituted proline esters via [3+2] cycloaddition between IV-methylated azomethine ylides and nitroalkenes has been reported.147 The stereochemistry of 1,3-dipolar cycloaddition of azomethine ylides derived from aromatic aldehydes and L-proline alkyl esters with various nitroalkenes has been reported. Cyclic and acyclic nitroalkenes add to the anti form of the ylide in a highly regioselective manner to give pyrrolizidine derivatives.148... 

Solutions of acetyl nitrate, prepared from fuming nitric acid and acetic anhydride, can react with alkenes to yield a mixture of nitro and nitrate ester products, but the /3-nitroacetate is usually the major product. ° Treatment of cyclohexene with this reagent is reported to yield a mixture of 2-nitrocyclohexanol nitrate, 2-nitrocyclohexanol acetate, 2-nitrocyclohexene and 3-nitrocyclohexene. °/3-Nitroacetates readily undergo elimination to the a-nitroalkenes on heating with potassium bicarbonate. /3-Nitroacetates are also reduced to the nitroalkane on treatment with sodium borohydride in DMSO. ... 

Solutions of nitric acid in chlorinated solvents can add to some alkenes to give nitrate esters. Some tertiary nitrate esters can be prepared in this way isobutylene (49) reacts with fuming nitric acid of 98.6 % concentration in methylene chloride to give ferf-butyl nitrate (50). However, the products obtained depend on both the substrate and the reaction conditions /3-nitro-nitrate esters, vic-dinitrate esters, /3-nitroalcohols and nitroalkenes have been reported as products with other alkenes. Oxidation products like carboxylic acids are also common, especially at elevated temperatures and in the presence of oxygen. The reaction of alkenes with fuming nitric acid is an important route to unsaturated nitrosteroids, which assumedly arise from the dehydration of /3-nitroalcohols or the elimination of nitric acid from /3-nitro-nitrate... 

Most of the current preparative methods of oximes from nitroalkenes are not versatile. Reduction of nitroalkenes by CrCl2 or NaH2P02 in the presence of palladium was reported to afford the corresponding oximes, but the yields are not satisfactory. Zn-acetic acid and Na2Sn02 reductions are limited to the preparation of ketoximes only. Electroreduction of alkenes was reported to yield mixmres of ketones and ketoximes, or oximes and acetals (or ketones) depending on the strucmre of nitroalkanes. 

Of the many substituted and functionalized alkenes that have been combined with diazo dipoles to give A -pyrazolines or products derived from them (i.e., A -pyrazolines, pyrazoles, cyclopropanes), only a selection will be mentioned. These include ot-alkylidene-cycloalkanones (62), -flavanones, -thioflavanones, -chroma-nones, and thiochromanones (63,64) a-arylidene-indanones and -indolones (65) diarylideneacetones (66) l-benzopyran-2(77)-ones (coumarins) (67,68) 4-nitro-1,2-oxazoles (69) 2-alkylidene-2-cyanoacetates (70) dimethyl 2,3-dicyanofuma-rate (71) tetracyanoethylene (72) tetraethyl ethylenetetracarboxylate (72) 1,4-quinones (35,73-75) 2-X-l,l,l-trifluoro-2-propene [X = Br, (76), SPh, SOPh, S02Ph (77)] nitroalkenes (78) including sugar nitroalkenes (79) 1-diethoxyphos-phoryl-1-alkenyl-sulfoxides (80) methyl 2-(acetylamino)cinnamate and -acrylate... 

Cyclic alkyl nitronates may be used in tandem [4+2]/[3+2] cycloadditions of nitroalkanes, and this reaction has been extensively studied by Denmark et al. (64,333-335). In recent work, they developed the silicon-tethered heterodiene-alkene 219 (Scheme 12.63). Steric hindrance and the fact that both the nitroalkene and the a,p-unsaturated ester in 219 are electron deficient renders the possibility of self-condensation. Instead, 219 reacts with the electron-rich chiral vinyl ether 220 in the presence of the catalyst 224 to form the intermediate chiral nitronate 221. The tandem reaction proceeds from 221 with an intramolecular 1,3-dipolar cycloaddition to form 222 with 93% de. Further synthetic steps led to the formation of ( )-detoxinine 223 (333). A similar type of tandem reaction has also been applied by Chattopadhyaya and co-workers (336), using 2, 3 -dideoxy-3 -nitro-2, 3 -didehydrothymidine as the starting material (336). 

The most reactive Michael acceptors, such as alkylidene malonates, gem-dicyanoalkenes and nitroalkenes, react with a-halozinc esters in a conjugate fashion. Beautiful examples were offered by two stereocontrolled conjugate additions to piperidinone 102 and pyrro-lidinone 104 leading to optically active bicyclic lactams 103147 (equation 60) and 105 (equation 61)148. With these electron-poor alkenes a Grignard two-step protocol is to be adopted in order to avoid the single electron transfer reactions from the metal to the Michael acceptor, which should afford olefin dimers. The best solvent is found to be a... 

Nitroalkenes (see 30) are easily made from nitro-alkanes and aldehydes and take part as dieno-philes in Diels-Alder reactions (chapter 17). The products can, as usual, be converted into amines or ketones. The stimulant fencamfamin 39 disconnects to the obvious Diels-Alder adduct 41 from cyelopentadiene 42 and the nitro-alkene 43. 

An allylic chiral center between the nitrile oxide and alkene groups can also affect the stereochemistry of INOC reactions. For example, the production of only the cycloadduct (191) in the reaction of the (Z)-nitroalkene (190) (Scheme 90), compared to the formation of a 3 1 mixture of the isoxazolines (193) and (194) from the ( )-isomer (192) (Scheme 91) (84ACR410) is a dramatic example of the influence of allylic 1,3-strain (89CRV1841) on these processes. 

Nitiyl iodide, from iodine vdth ver nitrite or from NO2 and iodine, adds to alkenes, generally in ether at room temperature, by a radical mechanism. Yields are 50-90%. The products yield nitroalkenes on treatment wiA base, a sequence used recently in the preparation of intermediates (Aidi=CMeN02) for amphetamine analogs. The reaction is also a key step in the a-methylenebuty-lolactone synthesis shown in Scheme 88. ... 

Acetyl nitrate (or nitryl acetate, Ac0NO2), prepared from nitric acid and acetic anhydride, reacts with simple acyclic and cyclic alkenes to give complex mixtures of nitro acetates, nitro nitrates and nitroalkenes, which are often difficult to separate12 103, The reaction with unsubstituted cycloalkenes was recently reexamined and a complex mixture of products, including allylic and homoallylic nitroalkenes, 1,2-, 1,3- and 1,4-nitro acetates, and 1,4-nitro nitrates, was identified104. These experimental observations are best accommodated by the proposal, supported by theoretical calculations, that the initial reaction of acetyl nitrate with alkene substrates is a [2 + 2] addition of the nitryl cation to the C-C double bond to form a cyclic cationic intermediate. 

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