Nitroalkanes alkylation with

The [Cp IrCl2]2 and [IrCl(cod)]2 catalysts have also been used in the alkylation of barbituric acid [43] and nitroalkanes [44] with primary alcohols. 

An earlier series of experiments established useful synthetic transformations involving carboxylation of ketones and nitroalkanes to yield P-keto acids and a-nitro acids respectively (Scheme 94).362 363 The reagent is methylmagnesium carbonate and the intermediate (130) can be alkylated with concomitant decarboxylation to provide greater versatility. These reactions can also be extended to ketone functions in imidazoline- and oxazolidine-diones (Scheme 95).364,365... 

Rhenium sulfide was the most active and hydrogenated excess ketone to the corresponding alcohols. The platinum metal sulfides were found to be more active than the base metal sulfides and highly selective for the formation of (V-alkylarylamines. They usually produce a pure product with little or no side reactions, require no excess above the stoichiometric amount of ketone, and are active at relatively low pressures of hydrogen. An example with (V-phenyl-p-phcnylencdiaminc is shown in eq. 6.15.37 Platinum metal sulfides may also be used for the reductive alkylation of aliphatic amines and their nitroalkane precursors with aliphatic ketones. 

White found that highly acidic C-H nucleophiles were required for a successful oxidative coupling reaction and used nitroalkanes 52 with electron-withdrawing substituents. In virtually all cases, the oxidative alkylation of 51 resulted in the... 

Among other reactions, the bis-metallated species (151) derived from nitroalkanes condense with dialkyl carbonates to give comp>ounds (152), in 60—80% yield, which can serve as precursors of both a-amino-acids and a-hydroxyamino-esters as well as a-keto-esters. Oxazolin-5-ones (153) can be alkylated at the 4-position by alkyl halides in hot DMF containing HMPA and ethyldi-isopropylamine. Yields are good (60—90%) for allylic, benzylic, and propargylic halides but otherwise poor (e.g. 32% with EtI) under these conditions acid hydrolysis of the products affords substituted a-amino-acids. Mesoionic l,3-oxazol-5-ones (154), obtained from imidoyl chlorides and acyl-tetracarbonylferrates, react with alcohols to give N-acyl-a-amino-acid esters. ... 

Nitroparaffias (or nitroaLkanes) are derivatives of the alkanes ia which one hydrogen or more is replaced by the electronegative nitro group, which is attached to carbon through nitrogen. The nitroparaffins are isomeric with alkyl nitrites, RONO, which are esters of nitrous acid. The nitro group ia a nitroparaffin has been shown to be symmetrical about the R—N bond axis, and may be represented as a resonance hybrid ... 

Reaction of various pyridazine derivatives with nitromethane or nitroethane in DMSO affords the corresponding 5-methyl and 5-ethyl derivatives. The reaction proceeds as a nucleophilic attack of the nitroalkane at the position 5. In this way, 3,6-dichloro-4-cyano-pyridazine, 4-carboxy- and 4-ethoxycarbonyl-pyridazin-3(2//)-ones and 4-carboxy- and 4-ethoxycarbonyl-pyridazin-6(lH)-ones can be alkylated at position 5 (77CPB1856). 

Alkyl mercury halides participate in a photo-sdmidated rathcM chain reacdon of the anion of nitroalkanes Isee Eq. 5.38 in which a 375-W sun lamp Is used." Primary, secondary, and ternary alkyl rathcMs generated from alkyl mercury halides react with the anion of ttitroalkanes to form new C-C bonds. 

AlkenyldQon using nitroalkanes foUowedby theselecQve reducQonof the double bends with NiCl and NdBbb, can be regarded as the addition of alkyl aruons to electron-deficient alkenes... 

A proof for the formation of alkyl radicals was found by their addition to the aci-nitromethane anion (CH2=N02 ) and by their reaction with p-benzoquinone to give the optically active nitroalkane radical-anion and the semiquinone radicals, respectively. In the case of di-r-butyl sulfoxide the f-butyl radical was observed directly by its absorption spectra. 

The reaction of alkyl halides with metal nitrites is one of the most important methods for the preparation of nitroalkanes. As a metal nitrite, silver nitrite (Victor-Meyer reaction), potassium nitrite, or sodium nitrite (Kornblum reaction) have been frequently used. The products are usually a mixture of nitroalkanes and alkyl nitrites, which are readily separated by distillation (Eq. 2.47). The synthesis of nitro compounds by this process is well documented in the reviews, and some typical cases are listed in Table 2.3.92a Primary and secondary alkyl iodides and bromides as well as sulfonate esters give the corresponding nitro compounds in 50-70% yields on treatment with NaN02 in DMF or DMSO. Some of them are described precisely in vol 4 of Organic Synthesis. For example, 1,4-dinitrobutane is prepared in 41 -46% yield by the reaction of 1,4-diiodobutane with silver nitrite in diethyl ether.92b 1-Nitrooctane is prepared by the reaction with silver nitrite in 75-80% yield. The reaction of silver nitrite with secondary halides gives yields of nitroalkanes of about 15%, whereas with tertiary halides the yields are 0-5%.92c Ethyl a-nitrobutyrate is prepared by the reaction of ethyl a-bromobutyrate in 68-75% yield with sodium nitrite in DMF.92d Sodium nitrite is considerably more soluble in DMSO than in DMF as a consequence, with DMSO, much more concentrated solutions can be employed and this makes shorter reaction times possible.926... 

Thus, the reaction of alkyl halides and a-halo esters with sodium nitrite provides a very useful synthetic method for nitroalkanes and a-nitro esters. However, ethyl bromoacetate is exceptional in that it fails to give ethyl nitroacetate on treatment with sodium nitrite.93 This is due to the acidic hydrogen of the ethyl nitroacetate, which undergoes a further reaction with sodium nitrite to give the oxidized products (see Section 6.1, which discusses the Nef reaction). In a similar way, the reaction of benzyl bromide with sodium nitrite at 25 °C gives benzoic acid predominantly. To get phenylnitromethane, the reaction must be carried out at low temperature (-16 °C) (Eq. 2.48).93... 

An experimentally simple procedure for stereoselectively preparing P-nitro alcohols has been developed. The alkyl nitronates, formed by the action of n-butyllithium on nitroalkanes in THF solution, react with aldehydes in the presence of isopropoxytitanium trichloride at room temperature to give the P-nitro alcohols enriched in the anri-diastereoisomers (Eq. 3.71).112... 

Thus, the direct alkylation of the anions derived from nitroalkanes with alkyl halides has some difficulties, and such difficulties are partially overcome by the radical reaction or transition metal catalyzed reactions, as discussed in Sections 5.4 and 5.5. 

The ability of a nitro group in the substrate to bring about electron-transfer free radical chain nucleophilic substitution (SrnI) at a saturated carbon atom is well documented.39 Such electron transfer reactions are one of the characteristic features of nitro compounds. Komblum and Russell have established the SrnI reaction independently the details of the early history have been well reviewed by them.39 The reaction of p-nitrobenzyl chloride with a salt of nitroalkane is in sharp contrast to the general behavior of the alkylation of the carbanions derived from nitroalkanes here, carbon alkylation is predominant. The carbon alkylation process proceeds via a chain reaction involving anion radicals and free radicals, as shown in Eq. 5.24 and Scheme... 

Oxidative cross-coupling reactions of alkylated derivatives of activated CH compounds, such as malonic esters, acetylacetone, cyanoacetates, and certain ketones, with nitroalkanes promoted by silver nitrate or iodine lead to the formation of the nitroalkylated products.67 This is an alternative way of performing SRN1 reactions using a-halo-nitroalkanes. 

Monoanions derived from nitroalkanes are more prone to alkylate on oxygen rather than on carbon in reactions with alkyl halides, as discussed in Section 5.1. Methods to circumvent O-alkylation of nitro compounds are presented in Sections 5.1 and 5.4, in which alkylation of the a.a-dianions of primary nitro compounds and radial reactions are described. Palladium-catalyzed alkylation of nitro compounds offers another useful method for C-alkylation of nitro compounds. Tsuj i and Trost have developed the carbon-carbon bond forming reactions using 7t-allyl Pd complexes. Various nucleophiles such as the anions derived from diethyl malonate or ethyl acetoacetate are employed for this transformation, as shown in Scheme 5.7. This process is now one of the most important tools for synthesis of complex compounds.6811-1 Nitro compounds can participate in palladium-catalyzed alkylation, both as alkylating agents (see Section 7.1.2) and nucleophiles. This section summarizes the C-alkylation of nitro compounds using transition metals. 

Asymmetric synthesis of tricyclic nitro ergoline synthon (up to 70% ee) is accomplished by intramolecular cyclization of nitro compound Pd(0)-catalyzed complexes with classical C2 symmetry diphosphanes.94 Palladium complexes of 4,5-dihydrooxazoles are better chiral ligands to promote asymmetric allylic alkylation than classical catalysts. For example, allylic substitution with nitromethane gives enantioselectivity exceeding 99% ee (Eq. 5.62).95 Phosphi-noxazolines can induce very high enatioselectivity in other transition metal-catalyzed reactions.96 Diastereo- and enantioselective allylation of substituted nitroalkanes has also been reported.9513... 

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