Reductive nitroarene alkylation

To our knowledge, reactions of organometallic compounds with nitroarenes lead, as a rule, to mixtures of reduction and alkylation (or arylation) products.2 11 Only few examples have been described where the reactions proceed with the formation of N, /V-disubstituted hydroxylamine and/or secondary amines.4-6-9... 

Synthesis of ortho alkyl anilines (Rosini) by reductive C-alkylation of nitroarenes. Also synthesis of indoles (Bartoli) by reaction of 2-substituted nitroarenes with vinyl Grignard reagents. 

As discussed in Chapter 9, various nucleophiles can be introduced at the ortho position of nitroarenes via the VNS process. This provides a useful strategy for the synthesis of indoles. One of the most attractive and general methods of indoles and indolinones would be the reductive cyclization of a-nitroaryl carbonyl compounds (Eq. 10.54). The VNS and related reactions afford a-nitroaryl carbonyl compounds by a simple procedure. For example, alkylation of 4-fluoronitrobenzene with a lactone silyl enol ether followed by reductive cyclization leads to tryptophols (Eq. 10.55).73... 

The cyanomethylation of nitroarenes followed by alkylation and reductive cyclization yields indoles (see Chapter 9, which discusses the VNS reactions) (Eq. 10.56).74... 

Alkyl nitroarenes may on reduction lose a proton from the side chain either during the acid-catalyzed rearrangement of the arylhydroxylamine or from the parent compound, from which an electrogenerated base (EGB) may abstract one of the relatively acidic protons a. to the nitroaryl. 

PtCl2(PPhj)2] in the presence of SnCU and EtsN, both in catalytic amounts, catalyzes the reduction of nitroarenes to aniline derivatives by CO and water (equation 74). SnCU was less effective. The reaction requires raised temperature and CO pressure. If alcohols were used in the same reaction in place of water, alkyl aryl carbamates were produced (equation 144). The catalyst precursor was again [PtCU(PPh3)2] with SnCU and EtjN. 

Bis(silyl)ketene acetals undergo silatropic ene reaction with nitrosobenzene to give N-hydroxyamino acid derivatives. When allylmagnesium chloride is reacted with nitroarenes, unstable adducts result. Reduction of these adducts with LAH in the presence of palladium on charcoal leads to A -allyl-W -aryl-hydroxylamines (73 Scheme 15). With alkyl Grignard reagents this reaction is negligible. ... 

Reductions. In the reduction of organic compounds by Sm some additives are often included. For example, iodine is present in the system for the reduction of nitroarenes and aryl azides, and sodium alkyl thiosulfates.- ... 

Titanium(IV) chloride and titanocene dichloride have catalytic effects on the reduction, e.g., in the transformation of alkyl thiocyanates to dialkyl disulfides and nitroarenes to aryl amines, respectively. 

Some halogenated alkyl groups that can undergo reductive dehalogenation (Fig. 3, reaction 7) Nitroarenes that can be reduced to nitro anion-radicals, nitrosoarenes, nitroxides, and hydroxylamines (Fig. 7, reaction 4)... 

The main synthesis of oxindoles is simple and direct and involves an intramolecular Friedel-Crafts alkylation reaction as the cyclising step. Also straightforward in concept is the displacement of halogen from an ort/to-halo-nitroarene with malonate, this leading to an oxindole after decarboxylation and reduction of the nitro group with spontaneous lactamisation. ... 

Catalytic reduction in methanol using decaborane as the hydrogen source successfully saturates alkenes and alkynes and converts nitroarenes to arylamines. Concurrent A -alkylation to afford ArNHCHRR occurs when a carbonyl compound (RR C=0) is present. " ... 

Reduction. A selective reduction of nitroarenes to arylamines occurs with Zn in near-critical water (at 250°). Cyclization that follows reduction is expected in the case of 2-nitroaryl compounds containing a leaving group at proper distance, ArN02 is converted to ArNR2 by a reductive alkylation process in protic solvents (promoted by Zn or Sn). ... 

Alkylation of nitroarenes. Nitroarenes are alkylated by Grignard reagents with concomitant reduction of the nitro group in the presence of Cul in catalytic amounts. ... 

B5mn E, Hong B, De Castro KA, Lim M, Rhee H (2007) One-pot reductive mono-A-alkylation of aniline and nitroarene derivatives using aldehydes. J Org Chem 72(25) 9815-9817. doi 10. 1021/jo701503q... 

Primary Amines—Several new and improved methods for the preparation of aromatic primary amines have been described. " The catalytic reduction of aromatic nitro-compounds to amines with hydrazine hydrate in the presence of iron(iii) oxide hydroxide proceeds smoothly and in high yields. Nitroarenes (1) react with Grignard reagents in the presence of copper(i) iodide, and are alkylated selectively on the aromatic moiety, accompanied by reduction of the nitro-group to the amine (Scheme 1). Both aryl and alkyl azides are rapidly... 

Reductions of aldehydes and ketones to alcohols proceed at slower rates with AERs in BH4 form than with NaBH4 in ethanol.a,j8-Unsaturated carbonyl compounds are reduced by BH4 in a gel AER to the allylic alcohols. Cyanoborohydride ion in a macroporous AER effects reductive aminations of ketones and ammonia to primary amines, reductive methylations of primary amines to the N,iV-dimethyl tertiary amines with aqueous formaldehyde, reductions of N-alkyl- and AT-acyl-pyridinium ions to tetrahydropyridines, and reductions of primary alkyl halides to alkanes. Nitroarenes are reduced to amines, the bromide of a-bromocarbonyl compounds is replaced by hydride, and 1,2-dibromoalkanes give alkenes by treatment with HFe(CO)4 in a macroporous AER. 

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