Alkylation of nitro compounds

C-Alkylation takes place in the reaction of methyl nitroacetate with alkyl halides the products are useful intermediates for preparing amino acids (Eq. 5.1).2 The requisite nitro acetate is prepared by self condensation of nitromethane.3 

Preparation of Merrifield resin-bound nitro acetates, which is a suitable building block for the development of combinatorial solid phase synthesis, is reported.4 The anion of ethyl nitro acetate is generated in DMF by an electrochemical method using Pt cathode, magnesium rod anode, and tetrabutylammonium bromide as an electrolyte. Alkylaton of this anion with alkyl halides gives mono-alkylated products in 80% yield.5 

The reactivity of carbon is much enhanced by the double deprotonated intermediates of nitro compounds. Except for nitromethane, other nitroalkanes are alkylated to give the C-alkylated products in 50-60% yield by this procedure (see Eq. 5.4).9 10 

Mosher and coworkers have adopted this strategy for the enantioselective synthesis of 2,3-dideoxy-3-nitro-furanosides and pyranosides using chiral nitronate dianions, as shown in Eq. 5.5.11 

The dianion derived from methyl 3-nitropropanoate is formed on treatment with LDA, and it is alkylated by alkyl halides exclusively at the 2-position (Eq. 5.6). Elimination of HN02 with DBU in THF furnishes methyl a-methylenealkanoate (see Section 7.3, which discusses alkene formation).12 

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Chemoselective C-alkylation of the highly acidic and enolic triacetic acid lactone 104 (pAl, = 4.94) and tetronic acid (pA, = 3.76) is possible by use of DBU[68]. No 0-alkylation takes place. The same compound 105 is obtained by the regioslective allylation of copper-protected methyl 3,5-dioxohexano-ate[69]. It is known that base-catalyzed alkylation of nitro compounds affords 0-alkylation products, and the smooth Pd-catalyzed C-allylation of nitroalkanes[38.39], nitroacetate[70], and phenylstilfonylnitromethane[71] is possible. Chemoselective C-allylation of nitroethane (106) or the nitroacetate 107 has been applied to the synthesis of the skeleton of the ergoline alkaloid 108[70]. 

ALKYLATION OF NITRO COMPOUNDS USING TRANSmON METAL CATALYSIS... 

A different kind of alkylation of nitro compounds uses carbanion nucleophiles that have a chlorine at the carbanionic carbon. The following process takes place ... 

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. 

Alkylation of Nitro Compounds In solution, AN exist in labile equilibrium (the so-called Hantzsch triangle, Scheme 3.2) (1). 

Tertiary arylamines were prepared in good yields by hydrogenation of an alcoholic solution of a nitro compound and an aldehyde over Raney Ni in the presence of triethy-lamine hydrochloride or, better, over platinum oxide in the presence of acetic acid (eq. 6.22).48 Base metal and platinum metal sulfides are also effective to the reductive alkylation of nitro compounds with ketones36,37 as in an example shown in eq. 6.23. 

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