P-Nitro ketones

Nitroalkanes react with Jt-deficient alkenes, for example, p-nitro ketones are produced from a,P-unsaturated ketones [41], whereas allylic nitro compounds have been prepared via the Michael-type addition of nitroalkanes with electron-deficient alkynes (Table 6.19). The reaction in either dimethylsulphoxide [42] or dimethyl-formamide [43] is catalysed by potassium fluoride in the presence of benzyltriethyl-ammonium chloride the reaction with dimethyl acetylenedicarboxylate is only successful in dimethylsulphoxide [42], Primary nitroalkanes produce double Michael adducts [42,44], A-Protected a-aminoacetonitriles react with alkynes under catalysed solidiliquid conditions to produce the Michael adducts [45] which, upon treatment with aqueous copper(Il) sulphate, are converted into a,p-unsaturated ketones. 

An interesting variant of these Michael-type additions is the 1,6-addition of the anion of type (29) to a dienyl sulfone as a route to tagetones and 1,4-addition to nitrostyrene to form P-nitro ketones. A key step in a synthesis of 11-deoxyanthracyclinone involves the regioselective reaction of coroplexed styrene with lithiated protected acetddehyde cyanohydrin. ... 

More complex products are obtained from cyclizations in which the oxidizable functionality and the alkene are present in the same molecule. y9-Keto esters have been used extensively for Mn(III)-based oxidative cyclizations and react with Mn(OAc)3 at room temperature or slightly above [4, 10, 11, 15], They may be cyclic or acyclic and may be a-unsubstituted or may contain an a-alkyl or chloro substituent. Cycloalkanones are formed if the unsaturated chain is attached to the ketone. y-Lactones are formed from allylic acetoacetates [10, 11]. Less acidic /3-keto amides have recently been used for the formation of lactams or cycloalkanones [37]. Malonic esters have also been widely used and form radicals at 60-80 °C. Cycloalkanes are formed if an unsaturated chain is attached to the a-position. y-Lactones are formed from allylic malonates [10, 11]. yff-Diketones have been used with some success for cyclizations to both alkenes and aromatic rings [10, 11]. Other acidic carbonyl compounds such as fi-keto acids, /3-keto sulfoxides, j8-keto sulfones, and P-nitro ketones have seen limited use [10, 11]. We have recently found that oxidative cyclizations of unsaturated ketones can be carried out in high yield in acetic acid at 80 °C if the ketone selectively enolizes to one side and the product cannot enolize... 

Using the fluorine-modified triazolium salt II as precatalyst, the desired p-nitro ketones 42 were obtained in veiy good yields and with high enan-tioselectivities (Scheme 20.20). Later, they successfully expanded the reactions to enals to give adducts 44 in good yields and with good enantioselectivities (Scheme 20.21). ... 

Polymeric -peroxides (3) from hydrogen peroxide and lower carbon ketones have been separated by paper or column chromatography and have been characterized by conversion to the bis(p-(nitro)peroxybenzoates). Oligomeric peroxides (3, R = methyl, R = ethyl, n = 1-4) from methyl ethyl ketone have been separated and interconverted by suitable treatment with ketone and hydrogen peroxide (44). 

The N-carboxybenzoyl compound (2.7 g) was refluxed for 30 minutes with acetic anhydride (10 ml), the mixture taken to dryness (vacuum) and the residue heated with water. The cooled gummy product became granular on rubbing and crystallized from methyl ethyl ketone-petrol or aqueous ethanol in almost colorless needles, MP 184° to 186°C, of p-nitro-N-phthaloyl-D L-phenylalanine. 

The base-catalysed reaction of a-bromo-a,P-unsaturated ketones with aliphatic nitro compounds leads to 2-isoxazoline A-oxides by tandem conjugate addition-ring closure (Scheme 5) <95JOC6624>. A -Acyl-3-isoxazolin-5-ones are transformed into oxazoles by photolysis or by flash vacuum pyrolysis (Scheme 6) <96TL675>. 

Ketone B.P. M.P. 2 4-DinltrO phenyi hydrazone Semiear bazone Benzal Derivative Phenyi- hydrazone p-Nitro- phenyi hydrazone Other Derivatives... 

P-Nitro carbonyl compounds are important for synthesis of natural products. The reaction of alkyl vinyl ketones with sodium nitrite and acetic acid in THF gives the corresponding P-nitro carbonyl compounds in 42-82%.105 This method is better for the preparation of P-nitro carbonyl compounds than the nitration of the corresponding halides. 

Another method for improving the reactivity of nitro compounds is provided by the double deprotonation of nitroalkanes. In this case, the reaction with ketones affords P-nitro alcohols in 40-60% yield (Eq. 3.19).30... 

The Michael addition of a-nitro ketones to a,P-unsaturated ketones followed by radical denitration provides a useful strategy for the preparation of 1,4-diketones.134b 1-Phenylheptane-1,5-dione, isolated from the decayed heart wood of aspens, is prepared by this strategy (Eq. 4.127).174... 

The Michael addition of nitro compounds to a,P-unsaturated ketones or esters followed by reduction of the nitro to amino group is useful for the preparation of various heterocycles. This is presented in Chapter 10 (Synthesis of Heterocycles). 

Primary nitro compounds are good precursors for preparing nitriles and nitrile oxides (Eq. 6.31). The conversion of nitro compounds into nitrile oxides affords an important tool for the synthesis of complex natural products. Nitrile oxides are reactive 1,3-dipoles that form isoxazolines or isoxazoles by the reaction with alkenes or alky nes, respectively. The products are also important precursors for various substrates such as P-amino alcohols, P-hydroxy ketones, P-hydroxy nitriles, and P-hydroxy acids (Scheme 6.3). Many good reviews concerning nitrile oxides in organic synthesis exist some of them are listed here.50-56 Applications of organic synthesis using nitrile oxides are discussed in Section 8.2.2. 

Esters and ketones bearing P-nitro groups can be prepared in many ways. For example, the Diels-Alder reaction of methyl P-nitroacrylate is one typical case. Various cyclic dienes are prepared by this route, and the reactions of Eq. 7.121167 andEq. 7.122168 are exemplified. 

The Michael addition of nitroalkanes to a, P-unsaturated ketones gives y-nitroketones, which are converted into pyrroles by reduction of the nitro group with Bu3P and PhSSPh (Eq. 10.2).4... 

The a,P-unsaturated ketone (10 mmol) is stirred with the nitroalkane (40 mmol), K,CO, (0.7 g) and Aliquat (40 mg, 0.1 mmol) and the mixture is subjected to sonication at room temperature until the reaction is complete, as shown by GLC. The mixture is acidified with HC1 (1M) and extracted with Et20 (3 x 20 ml). The dried (MgS04) extracts are evaporated to yield the nitro ketone (>70%). 

The reduction of ketones containing nitro groups to nitro alcohols is best carried out by borohydrides. 5-Nitro-2-pentanone was converted to 5-nitro-2-pentanol in 86.6% yield by reduction with sodium borohydride at 20-25°. Other nitro ketones gave 48.5-98.7% yields, usually higher than were obtained by Meerwein-Ponruiorf reduction [907]. 2-Acetamido-3-(p-nitrophenyl)-l-hydroxypropan-3-one was reduced with calcium borohydride at — 30° to 70% of threo- and 10% of er7tAro-2-acetamido-3-(p-nitrophenyl)propane-l,3-diol while sodium borohydride afforded a mixture of the above isomers in 25% and 47% yields, respectively [902]. 

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... 

Diels-Alder reactionsThis reagent is more reactive in Dicls-Alder reactions than cyclohcxcnone. Treatment of the /i-nitro ketone with DBN effects elimination of HNO, to form the a,/ -enone.2 Thus the final products correspond to adducts of a "cyclohcxynone, but with reversed regioselectivity. 3-Nitro-2-cyclopentenone, m.p. 69- 7T, is also a useful dienophile (second example). 

Reaction CXXVlil. Action of Phenylhydrazine, etc., on Aldehydes and Ketones.—Phenylhydrazones of aldehydes and ketones are generally formed by warming these substances in aqueous-alcoholic solution with phenylhydrazine, phenylhydrazine acetate or phenylhydrazine hydrochloride in presence of excess sodium acetate. Derivatives of phenylhydrazine (e.g., p-nitro-phenylhydrazine) also react in a similar manner. 

Despite their high synthetic potential, when L-proline-catalyzed reactions are evaluated, catalytic amounts in the range 20 to 35% and use of excess ketone (usually 20% v/v) represent reaction parameters to be optimized. Experimental studies addressing this issue have been conducted and impressive solutions were found by the List group [23], As a model reaction the Mannich synthesis using p-nitro-... 

Kloetzel prepared various y-nitro ketones by a Michael-type condensation of nitroal-kanes with a,p-unsaturatcd ketones in the presence of diethylamine, and hydrogenated the y-nitro ketones thus obtained to the corresponding pyrrolidines in 51.5-94% yields over Raney Ni in methanol at 100°C and 6.9 MPa H2 in both the presence and absence of ammonia (eq. 9.30).55 It is noted that the hydrogenation of y-nitro phenyl ketones (R4 = Ph, eq. 9.30) over Raney Ni in the presence of ammonia yielded high yields of the corresponding pyrrolidines, which were obtained in only small quantities with use of platinum under the conditions of eq. 9.29. 

A small library of isoxazole fused azepines 39 was synthesised by the acid catalysed conjugate addition of 3,5-dimethyl-4-nitroisoxoazole 36 to a,p-unsaturated ketones 37 yielding the adduct 38 followed by tin(II) chloride reduction of the nitro group and imine formation <07ARK266>. 

Further uses of nitroalkanes are in 1,4-additions (Michael reaction) to a,p-unsaturated carbonyl compounds and the like. Recent reports deal with transformations of 1,4-nitro ketones, 7, into 1,4-keto aldehydes, 8, and cyclization to cyclopentenones.16... 

Ballini, R., Marotta, E., Petrini, M., Righi, P, and Rosini, G. 1990. Recent progress in the synthesis and reactivity of nitro ketones. A review. Organic Preparations and Procedures International, 22(6) 707-46. 

Dicarbonyl compounds.4 Michael addition of a-nitro ketones to methyl vinyl ketone (la) or acrylaldehyde (lb) catalyzed by P(QH5)3 provides the adducts 2, which are reduced by Bu3SnH to 1,5-dicarbonyl compounds (3). Additions to the enal proceed more rapidly than ones to the enone. 

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