Nitroketone synthesis

Scheme 64 MCRs from a-nitroketones synthesis of bicyclic macrolactones...

R. H. Fischer u. H.M. Weitz, Preparations and Reactions of Cyclic tz-Nitroketones, Synthesis 1980,261 -282. 

This class was first reported in 1924 and was formed 62HC(17)l) by cyclization of a-bromo-/3-aryl-y-nitroketones. The direct synthesis by oxygenation of 2-isoxazolines has not been reported. To date only 3-substituted derivatives have been prepared. Aryl-nitromethanes react with nitrostilbene to form isoxazoline A-oxide by a nitrile ion displacement (Scheme 138) <62HC(17)1, 68TL3375). 

A particular case of the synthesis of isoxazoles via -diketone derivatives is the preparation of 3-halogenoisoxazoles (11) from -nitroketones (9) treated with hydrogen halides. This inter-... 

As a new and practical synthesis of pyrroles, Zard and coworkers have presented the reduction of Y-nitroketones v/ith formamidinesiilfinic acid fEq. IC.Bi/... 

Baker s yeast reducdon of y-nitroketones offers the corresponding chiral nitro alcohols, which areusefid bndding blocks for the synthesis of chiral naniral compounds. For example, opdcally acdve 2-subsdnited pyrrolidine can be prepared using the chiral nitro alcohol fEq. 10.751. ... 

Because the a-nitroketones are prepared by the acylation of nitroalkanes (see Section 5.2), by the oxidation of (3-nitro alcohols (Section 3.2.3), or by the nitration of enol acetates (Section 2.2.5), denitration of a-nitro ketones provides a useful method for the preparation of ketones (Scheme 7.10). A simple synthesis of cyclopentenone derivatives is shown in Eq. 7.66.76... 

In a significant addition to the synthesis of 1,2,4-oxadiazoles (Scheme 41), Itoh et al. discovered that the treatment of nitriles with iron(lll) nitrate in the presence of acetone or acetophenone gives the 3-acetyl- or 3-benzoyl-l,2,4-oxadiazoles 260, proposing that enolization and nitration gives an a-nitroketone, which then undergoes an acid-catalyzed dehydration to give the nitrile oxides 259 <2005S1935>. 

Haloalkanes are readily oxidized to the corresponding aldehydes or ketones. The best yields are attained with secondary alcohols and unsaturated hydroxyl groups [5]. a-Nitroketones, which are valuable intermediates in organic synthesis, are... 

Solutions of acetyl nitrate have also been used for the synthesis of a-nitroketones from enol esters and ethers. ° ... 

Giorgi G, Miranda S, Lopez-Alvarado P, Avendano C, Rodriguez J, Menendez JC (2005) Unique Michael addition-initiated domino reaction for the stereoselective synthesis of functionalized macrolactones from alpha-nitroketones in water. Org Lett 7 2197-2200... 

Lemaire et al. have developed a efficient fructose-1,6-bisphosphate aldolase (FBPA)-mediated synthesis of aminocyclitol analogs of valiolamine [34], This one-pot route involves the formation of two C—C bonds where four stereocenters are created. The first C—C bond formation reaction is catalyzed by the aldolase, coupling DHAP to nitrobutyraldehydes the other one is the result of a highly stereoselective intramolecular Henry reaction occurring on the intermediate nitroketone under acidic conditions during the aldolase-catalyzed reaction and phytase-catalyzed phosphate hydrolysis coupled step (Scheme 4.13). 

The synthesis of unsymmetrical 1,4-diketones results from the conjugate addition of the nitronate anion (as the acyl anion equivalent) to an a,fi-unsaturated ketone [Method (6)].l47a The intermediate nitroketone is converted into the diketone by reduction with titanium(m) chloride at pH 1, or by ozono-lysis of the nitronate anion147b (cf. Section 5.7.7, p. 599). 

Gill, N. S. James, K. B. Lions, F. Potts, K. T. jS-Acylethylation with ketonic Mannich bases. The synthesis of some diketones, ketonic sulfides, nitroketones and pyridines. J. Am. 

Examples of such three-carbon synthons are 2-nitro-2-propen-l-yl acetates and piva-lates, which have been developed by Seebach and coworkers57,58 as reagents for [3 + 3] cyclizations with cyclic and acyclic ketone enamines. After workup these reactions give 4-nitrocyclohexanones. With enamines from prolinol methyl ether and cyclic ketones, enantiomerically pure compounds were obtained58. An example of such a [3 + 3] cyclization is the synthesis of bicyclic nitroketone 99 from nitroallylic ester 97 and enamine 98 (equation 18). 

A synthesis of 277-pyrroles has been reported, relying on reductive annulation of 7-nitroketones (Scheme 1), as exemplified by the transformation of the substrate 7 into the pyrrolidine 8, which was eventually dehydrogenated to the 277-pyrrole 9 by treatment with 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (DDQ) <2003TL3701>. 

Michael addition of nitromethane with this catalyst to the ketone (3) was used to obtain the nitroketone (4) in 84% yield. The reaction was the first step in a synthesis of ( )-ll-desoxyprostagIandin Ei, F, and F,j. 

Oxidative cyclization of o-aminoacylbenzenes is a much less common process for the synthesis of anthranils than the reductive cyclizations discussed in the previous section, mainly because the o-aminoketones are in many instances best prepared by reductive ring opening of anthranils (see Section III,C,3). Nevertheless, a few examples have been recorded. Oxidation of o-aminobenzophenones to the nitroketones using peroxytrifluoro-acetic acid, permaleic acid, or persulfuric acid proceed via the 3-phenyl-anthranil which occasionally is isolable.168 Caro s acid is also a useful oxidant.169... 

An ingenious use of 1,3-dithians in the synthesis of 1,4-diketones has been reported, and is illustrated in Scheme 86. The difficulties experienced in the Nef transformation of y-nitroketones into 1,4-diketones can be obviated ... 

The reduction of ketoximes with titanium(iu) chloride is noted in a partial synthesis of erythromycylamine in this case, the intermediate imine is stable and can be further reduced, though normally imine hydrolysis is rapid and ketones are obtained in high yield. This observation has been utilized to effect conversion of a nitro-compound into a ketone. In search of a route to 1,4-diketones via conjugate addition of a masked carbonyl anion to an ajS-unsaturated ketone, McMurry considered Michael addition with a nitro-alkane. Treatment of the resulting y-nitroketone with titanium(m) chloride afforded the required 1,4-diketone (148) in excellent yield, presumably by sequential intermediacy of the oxime and the imine this mild conversion avoids the harsh conditions of the alternative Nef procedure (Scheme 69). 

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