Activated C-H Compounds

The nitration of active methylene compounds generally proceeds via the reaction of carbanionic intermediates with an electrophilic nitrating agent such as alkyl nitrate (alkyl nitrate nitration). Details of this process are well documented in the reviews.38 The alkyl nitrate nitration method has been used extensively for the preparation of arylnitromethanes. The toluene derivatives, which have electron-withdrawing groups are nitrated with alkyl nitrates in the presence of KNH2 in liquid ammonia (Eqs. 2.19 and 2.20).39 

The sodium salts of 1,3,5,7-tetranitrocubane and 1,2,3,5,7-pentanitrocubane can be nitrated successfully with N204 in THF at low temperature. These reactions proceed by N204 oxidation of the anion to the radical and its combination with N02 (Eq. 2.23) 43 Such highly nitrated cubanes are predicted to be shock-insensitive, very dense, high-energy compounds with great potential as explosives and propellants. 

1-Nitrocyclopropane-l-carboxylate is prepared in 71% yield by nitration of the enolate derived from the cyclopropane carboxylate with isoamyl nitrate (Eq. 2.24). It is a precursor of 

A convenient preparative method for conjugated nitroalkenes has been developed based on the reaction of nitrogen oxides. Nitric oxide (NO) is commercially available and used in the industry for the mass production of nitric acid. Nitric oxide is currently one of the most studied molecules in the fields of biochemistry, medicine, and environmental science.47 Thus, the reaction of NO with alkenes under aerobic conditions is of a renewed importance.48 

There are many reports for nitration of alkenes using various nitrating agents, which proceeds via an ionic or radical addition process.49 Nitration of cyclohexene with acetyl nitrate gives a mixture of 3-and y-nitrocyclohexenes, 1,2-nitroacetate, and 1,2-nitronitrate. This reaction is not a simple ionic or radical process instead, [2+2] cycloaddition of nitryl cation is proposed.50 

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Addition of Active C-H Compounds to Dienes the Rhone-Poulenc Process for Geranylacetone - Geranylacetone is a precursor of isophytol, a key intermediate in the manufacture of vitamine E (tocopherol) (see Figure 16), the world market of which is 10 000 t/a at a price of 25-30 /kg tocopherylacetate.54... 

In view of the many coupling reactions of conjugate bases of activated C—H compounds with diazonium and diazo species, it is not surprising that carbanions from other source can act as coupling components, too, e.g. in (35-37) lo ... 

Trapping of 0(,P-Unsaturated Acylpalladium with Active C-H Compounds... 

Negishi, E., Lion, S.Y., Xu, C., Shimoyama, I. and Makabe, H. (1993) Intermolecular trapping of acylpalladium and related acylmetal derivatives wifli active C-H compounds. Journal of Molecular Catalpis A Chemical, 143, 279-286. 

The required nitrite esters 1 can easily be obtained by reaction of an appropriate alcohol with nitrosyl chloride (NOCl). The 3-nitroso alcohols 2 formed by the Barton reaction are useful intermediates for further synthetic transformations, and might for example be converted into carbonyl compounds or amines. The most important application for the Barton reaction is its use for the transformation of a non-activated C-H group into a functional group. This has for example been applied for the functionalisation of the non-activated methyl groups C-18 and C-19 in the synthesis of certain steroids. ... 

The addic compounds used can be compounds with N-H bonds (aromatic primary amines [1], azole heterocycles [2-5], sulfonamides [6]), or enoHzable compounds with activated C-H bonds [7,8]. 

The reactivity of these oxidants towards organic substrates depends in a rough manner upon their redox potentials. Ag(II) and Co(III) attack unactivated and only slightly activated C-H bonds in cyclohexane, toluene and benzene and Ce(IV) perchlorate attacks saturated alcohols much faster than do Ce(lV) sulphate, V(V) or Mn(III). The last three are sluggish in action towards all but the active C-H and C-C bonds in polyfunctional compounds such as glycols and hydroxy-acids. They are, however, more reactive towards ketones than the two-equivalent reagents Cr(VI) and Mn(VIII) and in some cases oxidise them at a rate exceeding that of enolisation. 

Given the ability of 14 electron fragments [(dtbpm)Pt(O)] and [(dcpm)Pt(O)] to activate C-H and C-Si bonds of inert organosilanes under very mild reaction conditions, it was of course no big surprise that Si-H activation reactions of silanes are possible as well. Hydrido-silyl complexes were formed in practically quantitative reactions if 14 or IS were used as precursors for the [(dtbpm)Pt(O)] fragment. Examples of Si-H insertion products, all stable, isolable compounds which could be fully characterized, are 25 - 27, and others have been made. 

Figure 5.33 Benzophenone-4-iodoacetamide reacts with sulfhydryl-containing compounds to give thioether linkages. Subsequent photoactivation of the benzophenone residue gives a highly reactive triplet-state ketone intermediate. The energized electron can insert in active C—H or N—H bonds to give covalent crosslinks.

The ruthenium-, rhodium-, and palladium-catalyzed C-C bond formations involving C-H activation have been reviewed from the reaction types and mechanistic point of view.135-138 The activation of aromatic carbonyl compounds by transition metal catalyst undergoes ortho-alkylation through the carbometallation of unsaturated partner. This method offers an elegant way to activate C-H bond as a nucleophilic partner. The rhodium catalyst 112 has been used for the alkylation of benzophenone by vinyltrimethylsilane, affording the monoalkylated product 110 in 88% yield (Scheme 34). The formation of the dialkylated product is also observed in some cases. The ruthenium catalyst 113 has shown efficiency for such alkylation reactions, and n-methylacetophenone is transformed to the ortho-disubstituted acetophenone 111 in 97% yield without over-alkylation at the methyl substituent. 

A very different neutrally charged complex for alkane activation has been reported recently and is shown in Scheme 34(A). The compound is a hydridoplatinum(II) complex bearing an anionic ligand based on the familiar nacnac-type, but with a pendant olefin moiety (97).This complex is extremely soluble in arenes and alkanes and activates C-H bonds in both types of hydrocarbons. This is indicated by deuterium incorporation from deuterated hydrocarbon into the substituents on the arene of the ligand and into the Pt hydride position (A A-d27, Scheme 34). The open site needed for hydrocarbon coordination at Pt(II) is created by olefin insertion instead of anion or solvent substitution (97). 

Caulton and coworkers found that fluoride ligands in certain Ir complexes promote oxidative addition reactions [44]. This group s results showed that the fluoride complex lr(H)2F(P Bu2Ph)2 rapidly activated C—H bonds under dehydrogenation conditions. The reactive intermediate in these reactions may be a fluoro-bridged analogue of compounds 4-12, namely [lr(p-F)(P Bu2Ph)2]2. This would explain the improved reactivity in the Ir-catalyzed OHA reaction in the presence of cocatalytic naked fluoride . 

Dicarbonyl compounds are widely used in organic synthesis as activated nucleophiles. Because of the relatively high acidity of the methylenic C—H of 1,3-dicarbonyl compounds, most reactions involving 1,3-dicarbonyl compounds are considered to be nucleophilic additions or substitutions of enolates. However, some experimental evidence showed that 1,3-dicarbonyl compounds could react via C—H activations. Although this concept is still controversial, it opens a novel idea to consider the reactions of activated C H bonds. The chiral bifunctional Ru catalysts were used in enantioselective C C bonds formation by Michael addition of 1,3-dicarbonyl compounds with high yields and enantiomeric excesses. ... 

Certain diazo compounds can be photolyzed with UV light to generate highly reactive carbenes (Reaction 48). Similar to nitrenes, carbenes can insert into active C—H or... 

One-electron oxidation systems can also generate radical species in non-chain processes. The manganese(III)-induced oxidation of C-H bonds of enolizable carbonyl compounds [74], which leads to the generation of electrophilic radicals, has found some applications in multicomponent reactions involving carbon monoxide. In the first transformation given in Scheme 6.49, a one-electron oxidation of ethyl acetoacetate by manganese triacetate, yields a radical, which then consecutively adds to 1-decene and CO to form an acyl radical [75]. The subsequent one-electron oxidation of an acyl radical to an acyl cation leads to a carboxylic acid. The formation of a y-lactone is due to the further oxidation of a carboxylic acid having an active C-H bond. As shown in the second equation, alkynes can also be used as substrates for similar three-component reactions, in which further oxidation is not observed [76]. 

An unsaturated compound in the course of its isomerization in magnesium-containing films performs two functions (i) it forms a catalyst when the Mg4 cluster is inserted into the activated C-H bond, and (ii) it acts as a reaction substrate. The stages of the synthesis of the catalyst and isomerization can be separated. For example, anthracenyltetramagnesium hydride can be preliminarily obtained in anthracene-magnesium films, and then it can be used as a catalyst. The introduction of this cluster compound into a solution of allylbenzene or methylindene at room temperature ensures high yields of multiple bond migration products. 

By far, the most studied chlorinating peroxidase is CPO (in particular that from Caldariomyces fumago, which is involved in the biosynthesis of the chlorometa-bolite caldariomycin). CPO is able to halogenate (Cl, Br) activated C-H bonds, such as those of 1,3-dicarbonyl compounds. The reaction can afford both the monohalogenated compound and the dihalogenated product (and also mixed chloro/bromo compounds) [89-92] (Fig. 6.8a). 

Finally a carbene compound with a U=C bond is Cp3U=CHPMe3.61 Various alkyl and hydrido Cp species can catalyze oligomerization of terminal acetylenes, activate C-H bonds, hydrogenate alkenes, and so on.62... 

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