Unsaturated Nitro Compounds

Conjugate addition to unsaturated nitro-compounds, using the reaction between 1-trimethylsilyloxycyclohex-l-ene and 2-nitropropene, under the influence of SnCI4, to give 2-acetonylcyclohexanone (i.e. the nitrocompound acts as an umpoiung reagent for an acetone moiety). 

Amide (1) was needed for a synthesis of an isoquinoline. Disconnecting the amide reveals the amine (2) which could be made by reduction of an unsaturated nitro compound. The a, -disconnection is simple. 

Whereas secondary nitroalkanes such as 1-nitrocyclohexane 1766 are reduced to the corresponding oximes, for example 1767 [24], primary nitro compounds such as a-nitro-o-xylene 1768 or unsaturated nitro compounds such as 1770 are transformed into nitriles such as 1769 and 1771 [24] (Scheme 12.6). 

The enantiomeric reduction of 2-nitro-l-phenylprop-l-ene has been studied in a range of Gram-positive organisms including strains of Rhodococcus rhodochrous (Sakai et al. 1985). The enantiomeric purity of the product depended on the strain used, the length of cultivation, and the maintenance of a low pH that is consistent with the later results of Meah and Massey (2000). It has been shown that an NADPH-linked reduction of a,p-unsaturated nitro compounds may also be accomplished by old yellow enzyme via the flcf-nitro form (Meah and Massey 2000). This is formally analogous to the reduction and dismutation of cyclic enones by the same enzyme (Vaz et al. 1995), and the reductive fission of nitrate esters by an enzyme homologous to the old yellow enzyme from Saccharomyces cerevisiae (Snape et al. 1997). 

The photochemistry of unsaturated nitro compounds has been investigated by Chapman and co-workers.<63) Photolysis of 9-nitro-anthracene in degassed solutions leads to anthraquinone and 10,10 -bianthrone ... 

The first step in this domino process is the formation of an a, 3-unsaturated nitro compound which reacts with the amino functionality in 2-547. 

Giomi s group developed a domino process for the synthesis of spiro tricyclic nitroso acetals using a, 3-unsaturated nitro compounds 4-163 and ethyl vinyl ether to give the nitrone 4-164, which underwent a second 1,3-dipolar cycloaddition with the enol ether (Scheme 4.35) [56]. The diastereomeric cycloadducts formed, 4-165 and 4-166 can be isolated in high yield. However, if R is hydrogen, an elimination process follows to give the acetals 4-167 in 56% yield. 

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. 

The addition-elimination reaction of hetero-atom-substituted nitroalkenes provides functionalized derivatives of unsaturated nitro compounds.26 Nitroenamines are generally prepared from a-nitro ketones and amines (see Chapter 5 regarding acylation of nitro compounds).26... 

Certain a,/ -unsaturated nitro compounds are known to undergo photorearrangement to ketooximes as illustrated by the conversion of 1 -(3-pyridyl)-... 

Preparation of 2-dimethoxyphosphinyl-2-methoxy-2-phenylacetaldehyde oxime — Reaction of an unsaturated nitro compound with a trialkyl phosphite in the presence of an alcohol... 

Conjugate alkylation of nitroalkenes. R3A1 or the etherate reacts rapidly with a,p-unsaturated nitro compounds to form products of 1,4-addition.1 Example ... 

The base-catalysed Michael addition of a,/J-unsaturated nitro compounds 363 to electron-deficient olefins 364 (R4 = Ac, CC>2Me or CN) results in the formation of ally lie nitro compounds 365 aldehydes give alcohols 366 in this reaction409. 

Reduction of a, -unsaturated nitro compounds (29) affords the corresponding oximes (30) in high yields when electrolysis is carried out at —0.4 V (vs SCE) at a mercury or graphite electrode in aqueous isopropanol containing 0.1 M H2SO4 (equation 7)49. Reduction at —1.1 V affords the secondary amine (31) in fair yields. Isolated double bonds elsewhere in the molecule are not affected. 

Electrochemical reduction of the a, -unsaturated nitro compounds 32 in acetonitrile containing tetraethylammonium tosylate affords the corresponding hydrodimer in 37%... 

TABLE 11.25 Selective hydrogenation of unsaturated nitro compounds ... 

The orientation of substituents in the isomeric thiophthens and the synthesis of the solid isomer was reported. This solid isomer of thioph-thene was prepared by the reduction of thiophthene-3-ol with LiAlH4 (14). Finally, LiAlH4 was successfully utilized for the reduction of thienyl-nitroolefins (31) and other aromatic unsaturated nitro compounds (31 a). 

With aldehyde donors, the reactions are generally syn selective. A range of acceptors can be used, including a,p-unsaturated nitro compounds [72, 270, 274-281], a,p-unsaturated ketones [71, 282-285], vinyl phosphonates [286] and vinyl sulfones [287] etc. (Scheme 27). So far, no general anti selective... 

With ketone donors, both syn and anti selective reactions are possible. Typically, a,p-unsaturated nitro compounds are used as acceptors. The majority of these reactions are syn selective (Scheme 28) [94, 269, 271, 278, 279, 288-309]. This is a result of favored formation of the (fj-configured enamine and favorable electrostatic interactions between the nitro group and the enamine (Scheme 29) [290, 291, 310]. Of the known anti selective reactions, primary amine-thiourea catalysts such as 158 appear to perform best (Scheme 28) [271, 299, 301]. 

Hydrogenation of unsaturated nitro compound 37 (10% Pd/C, toluene) gives a saturated amino intermediate that can be treated with PTSA under Dean-Stark conditions to give the target keto isomer of cryptoheptine 38 in a 44% two-step yield (Scheme 7 (2000JNP643)). 

Readily available a,/3-unsaturated nitro compounds such as 77 undergo facile reduction into aUtylhydroxylamines of type 78 (equation 55) with borane/THF complex in the presence of catalytic amounts of sodium borohydride 74 ... 

When the stereogenic center is situated at the allylic position, as in nitroethyl ethers derived from 5,6-unsaturated nitro compounds, only the endo-isomer (trans) of the bicyclic structure was formed (Scheme 6.45) (256). 

Reduction of nitroalkenes. a, p-Unsaturated nitro compounds can be reduced to hydroxylamines by BH3 THF in the presence of a catalytic amount of sodium borohydride (equation I).1... 

The presence of functional groups in the heterocycle frequently determines the nature of the photoreaction observed. The major product of irradiation of 2-methoxyfuran (191) in the gas phase or in solution is the lactone (192).157 Similarly, 2-nitrofuran (193) undergoes a photoreaction typical of a,f -unsaturated nitro compounds to give the oxime (194) by the pathway shown in Scheme 13.158 A different process is observed, however, on irradiation of thenitrovinylbenzo[6]furan(195) to give the 6-hydroxy-l,2-oxazine(196)159 this transformation is viewed as proceeding via an electrocyclization pathway (Scheme 14) for which there is a precedent in the known photochromism of nitrostyrenes. 

Although the reduction of nitro compounds is more widely applied in the aromatic series using procedures discussed in Section 6.5.1, p. 890, these are equally applicable to the reduction of primary or secondary nitroalkanes when these are readily available. a,/ -Unsaturated nitro compounds (arising for example from the Claisen-Schmidt reaction, Section 6.12.2, p. 1032) may be reduced to the saturated amine very effectively with sodium dihydrobis(2-methoxyethoxy)-aluminate ( Red-Al ). 

The reduction of a, P-unsaturated nitro compounds permits the introduction of amino-... 

Unsaturated nitro compound and nitriles do not usually suffer nucleophilic attack by enols or enolates and both are good at conjugate addition. The addition of the morpholine enamine 57 of cyclohexanone to 58 demonstrates that the nitro group is more effective than the ester at promoting conjugate addition.7... 

Other groups beside nitro can be reduced in the same step. So the diamine 19, needed for polyamine manufacture, could come from the unsaturated nitro compound 20 that would in turn come from an aldol reaction between the anion of nitromethane 1 and the aldehyde 21. This has a 1,5-diX relationship and acrylonitrile 23 is excellent at conjugate addition (chapter 21) so we can use isobutyraldehyde 24 as a starting material. 

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