By the Nef reaction

This reaction is of wide scope it is limited only by the availability of the appropriate 1,4-diketone. 1,4-Diketones are easily accessible, e.g. by the Nef reaction. 

Valendn and coworkers have studied extensively the reaction of enamines v/ith nltroalkenes. The reaction proceeds under rruld conditions to give y-nitroketones, which are converted into 1,4-diketones by the Nef reaction CEq. 4.65. ... 

Ballini and coworkers have used the Michael ddition of tutro compounds followed by the Nef reaction for the synthesis of vanons spiroketahc pheromones fScheme 4 21 ... 

Nitroalkenes react with lithium dianions of carboxylic acids or with hthium enolates at -100 °C, and subsequent treatment of the Michael adducts with aqueous acid gives y-keto acids or esters in a one-pot operation, respectively (Eq. 4.52).66 The sequence of Michael addition to nitroalkenes and Nef reaction (Section 6.1) provides a useful tool for organic synthesis. For example, the addition of carbanions derived from sulfones to nitroalkenes followed by the Nef reaction and elimination of the sulfonyl group gives a,P-unsaturated ketones (Eq. 4.53).67... 

A simple synthesis of allethrolone, the alcohol component of the allethrine (commercially important insecticide), is shown in Scheme 4.11. The conjugated addition of 3-phenylthio-5-hexene-2-one to 1-nitro-l-propene followed by the Nef reaction and aldol condensation gives allethrolone in good yield.68... 

The Michael addition of nitro compounds is a useful method for the preparation of various natural products. The Michael addition of nitroalkanes to dehydroalanines gives y-nitro-a-amino acids, which provides a convenient synthesis of side-chain modified a-amino acids (Eq. 4.114).152 Transformations of y-nitro-a-amino acid derivatives into a-amino acids occur by reductive denitration (see Section 7.2) into y-oxygenated a-amino acids by the Nef reaction (Eq. 

The base-catalyzed reaction of nitromethane with a-amidoatkyl sulfones gives the nitro compounds as in Eq. 4.117 the nitromethyl group is converted into a carboxylic group to give a-amino acids by the Nef reaction using KMn04.155... 

The Michael addition of nitroalkanes to a,P-unsaturated ketones followed by the Nef reaction has been extensively used as a method for the conjugated addition of acyl anions to enones (see Section 6.1, Nef Reaction). This strategy is one of the best methods for the preparation of 1,4-dicarbonyl compounds.156a h Various natural products have been prepared via this route.157 For example, r/.v-jasmone is prepared from readily available materials, as shown in Scheme 4.19.156f... 

Butadiene telomerization using nitroethane as a trapping reagent is applied to the total synthesis of the natural product, recifeiolide, where the secondary nitro group is converted into the ketogroup by the Nef reaction, and the terminal double bond is converted into the iodide via hydro alumination (Scheme 5.6).71... 

Nitro compounds are versatile precursors for diverse functionalities. Their conversion into carbonyl compounds by the Nef reaction and into amines by reduction are the most widely used processes in organic synthesis using nitro compounds. In addition, dehydration of primary nitro compounds leads to nitrile oxides, a class of reactive 1,3-dipolar reagents. Nitro compounds are also good precursors for various nitrogen derivatives such as nitriles, oximes, hydroxylamines, and imines. These transformations of nitro compounds are well established and are used routinely in organic synthesis. 

The TiCl3 solution is very acidic such that acid-sensitive compounds do not survive. In such cases, sodium acetate or ammonium acetate is added to the reaction mixture to control pH at 5-6.29 Highly functionalized substrates are synthesized by the Nef reaction using TiCl3 and sodium acetate, as shown in Eq. 6.19,30 andEq. 6.20.31... 

The reaction of tertiary nitro compounds with the sodium salt of nitromethane followed by the Nef reaction provides a good method forthe preparation of quaternary aldehydes (Eq. 7.10).8 Because the nitromethyl group can be transformed into other groups such as CN, C02H, or CH2NH2, the SRN I reaction of tertiary nitro compounds with the anion of nitromethane is a synthetically useful method (Kornblum reaction).10 For example, the nitromethylation of tertiary nitro compounds has been applied for preparing starting materials for cascade polymers (Eq. 7.11).9... 

The Diels-Alder reaction of nitroalkenes followed by the Nef reaction is frequently used in natural product synthesis.7 For example, Scheme 8.3 shows an elegant synthesis of rf/-mesem-brane starting from the Diels-Alder reaction of 1-arylnitroethene with l,3-butadiene.7a... 

Intramolecular [4+2] cycloaddition of E,E- or L.Z-nitrodienes gives tranr-nitronates or ci.v-nitronates, respectively, with high stereoselectivity (Eq. 8.96).153 These products have been converted into y-lactones by the Nef reaction. 

The pyrrolo[2,3-c/]pyrimidine anticancer agent is prepared utilizing, as a key sequence, Michael condensation of 2,6-diamino-4(.37/)-pyrimidinone with nitroalkenes, followed by the Nef reaction that leads to the annulated pyrrole ring (Eq. 10.67).98... 

In the six-carbon series,8 the selective hydrogenation of d-ardbo-tetraacetoxy-l-nitrohexene-1 gave crystalline l-nitro-l,2-didesoxy-D-aro o-hexitol tetraacetate in 79 percent yield. This product, on de-acety-lation followed by the Nef reaction, then gave D-ara6o-2-desoxyhexose ( 2-desoxy-D-glucose ), isolated as the benzylphenylhydrazone,60 in high yield. 

Scheme 9A Formation of cyclohexanone from aci-nitrocyclohexane by the Nef reaction.

The base-catalyzed addition of nitromethane to an aldehyde according to the Henry reaction, followed by the Nef reaction, is a classical method for elongation of the carbon chain in carbohydrate chemistry Facile (3-elimination of the hydroxy group allows the synthesis of a,(3-unsaturated aldehydes or... 

Reaction of nitroalkanes with Michael acceptors, followed by the Nef reaction, represents a versatile synthetic route for the preparation of 4-oxoalkanals, 1,4-diketonesand 4-oxo esters. 

As mentioned earlier (see Section III,2 p. 112), the acetamidonitro-alditols can conveniently be transformed into amino glycoses by the Nef reaction. The sequence is illustrated by the example19 of the nitrogalactitol 208, which afforded the d-talo (209) and D-galacto (210) acetamidonitroalditols in yields (after purification) of 44.5 and 23.5% 209 and 210 were converted into 2-acetamido-2-deoxy-D-talose (211) and 2-acetamido-2-deoxy-D-galactose (212), either individually, or without prior separation. In the latter instance, yields based on 208 were 55 and 36%, respectively. 

Aliphatic nitro compounds serve as good acyl anion equivalents. After electrophilic alkylation at the a-carbon atom, they can be converted into carbonyl compounds by the Nef reaction or by reductive hydrolysis with titanium(III) chloride. The a-nitro carbanions serve as excellent donors in Michael addition reactions with a, -unsaturated systems and therefore the sequence of Michael addition followed by reductive hydrolysis of the nitro group provides a good route to 1,4-dicarbonyl compounds. ds-Jasmone, for example, was readily obtained by using this strategy (1.111). 

This reaction has general application in the synthesis of aldehydes and ketones, especially for 1,4-diketones and dihydrofurans. The 1,4-diketones can be prepared by the combination of a Michael reaction between a nitroalkane and an O, y0-unsaturated ketone followed by a Nef reaction, whereas dihydrofurans can be synthesized by the Nef reaction followed by cyclohydration. 

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