Of Unfunctionalized Alkanes

While phenyliodine(ni) diacetate and TMSN3 are known to form PhI(N3)2 in solution and homolyticaUy cleave to the azide radical (see this section, below), the combination is sensitive to decomposition at elevated tanperatures. A more stable azide source was developed by Zhdankin and cowoikers. Azidoiodinane 11 is thermally stable and in fact needs a radical initiator to affect the radical reaction. Following radical initiation, hydrogen-atom abstraction leads to a carbon-centered radical 

A number of papers showcase a variety of hypervalent iodine reagents for the goal of oxidizing a benzylic C—H bond. While some might not consider this C—H activation, as the argument could be made that the benzylic position is already activated, these reactions will nonetheless be covered here. 

Under radical initiation conditions, typically peroxides, hypervalent iodine reagents can be homolytically cleaved to iodine-centered radicals. These iodine centered radicals abstract a hydrogen atom from a labile benzylic C—H bond to yield a resonance-stabilized benzylic radical. At this point in the mechanism, researchers seem divided on the next step. Some propose a second single electron transfer (SET) to form a benzylic carbocation, ° which undergoes ionic reactions to form product. Others suggest radical combination to form an alkyl halide or organic peroxide which reacts further under the reaction conditions to form product. 

The Fan group and Nicholas group independently propose the radical mechanism in the amination reaction they developed. While the source of the iodine-centered radical differs, the mechanistic concept is the same. An N-iodo species can homolytically cleave to a nitrogen-centered radical. Hydrogen atom abstraction from the benzylic C—H bond and iodine atom abstraction from the A-iodo species form a benzylic iodide. Substitution of the iodide with the amine yields the product. 

While not iodine-based, Inoue and coworkers also report an interesting animation of the benzylic position using A -hydroxyphthalimide 13 and dialkyl azodicarboxyl-ates 14. An oxygen-centered radical from the homolytic cleavage of the N—O bond of the hydroxyphthalimide abstracts the benzylic hydrogen atom. Addition into the N=N pi bond of the azodicarboxylate forms the C—bond. Treatment with zinc and acetic acid reveals the benzylic amine IS.  

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Oxidation of unfunctionalized alkanes is notoriously difficult to perform selectively, because breaking of a C-H bond is required. Although oxidation is thermodynamically favourable, there are limited kinetic pathways for reaction to occur. For most alkanes, the hydrogens are not labile, and, as the carbon atom cannot expand its valence electron shell beyond eight electrons, there is no mechanism for electrophilic or nucleophilic substitution short of using extreme (superacid or superbase) conditions. Alkane oxidations are therefore normally radical processes, and thus difficult to control in terms of selectivity. Nonetheless, some oxidations of alkanes have been performed under supercritical conditions, although it is probable that these actually proceed via radical mechanisms. 

For many years the activation of unfunctionalized alkanes has been the Holy Grail of organic synthesis and, indeed, it has only been during the past few years that catalysts have evolved which allow an alkane C—H bond to be selectively... 

The iridium(l) PCP pincer complexes 1 exhibit remarkable activity in the catalytic dehydrogenation of unfunctionalized alkanes (Scheme 12.1). The H2, which is formally produced during this process, may be transferred to either tert-butyleth-ylene (TBE) or norbomene (NBE) as a sacrificial hydrogen acceptor. For example, complex la converts cyclooctane (COA) to cyclooctene (COE) in the presence of TBE, which in turn is reduced to tert-butylethane (TBA ueo-hexane) [6]. 

The preparation of unfunctionalized alkanes on insoluble supports has only recently received attention. With the aim of preparing ever more elaborate molecules on solid phase, chemists are currently searching for robust methods to assemble complex carbon frameworks on insoluble supports. The synthesis of alkanes has also been investigated in this context. 

Heterogeneous Catalysts for the C-H Transformation of Unfunctionalized Alkanes 589 Robert Schlogl... 

In summary, the hydrogenation of non-functionahzed olefins has not consistently reached the high level of enantioselectivities observed with many functionalized substrates. In some cases, however, chiral titanocenes, chiral lanthanide complexes, and now chiral irdium phosphanodihydrooxazole complexes can achieve superior selectivities. With the establishment of a limited number of unfunctionalized alkane products which can be resolved by chiral GC or HPLC methods, the pace of research in this area could be accelerated. 

Fig. 9.17 Examples of self-assembly of nanoparticles by a) hydrophobic interactions via a shell of unfunctionalized n-alkanes. Depicted is a Schematic 2D Representation of the RS/ Au nanoparticle packing structure in the solid state. Domains or bundles of ordered al-kylthiolate chains on Au particles interdigitate into the chain domains of adjacent particles in order to compensate the free volume of the outer region of the alkyl shell (Reprinted with permission from [146] A. Badia, L. Cuc-cia, L. Demers, et al.,J. Am. Chem. Soc. 1997, 779, 2582-2592. Copyright 1997 American Chemical Society), b) Direct comparison of hydrophobic interactions and chemical bridg-...

Iridium PCP-Catalyzed Activation of C(sp )—H Bonds in Unfunctionalized Alkanes... 

Hydroxyl and substrate-derived alkoxyl radicals, produced via Eq. (3), are the two main oxidants in Gif chemistry which are capable of effecting H-atom abstraction from unfunctionalized alkanes (Eq. 5). In contrast, Eq. (4) serves as a provider of Fe(II) ions and peroxyl radicals, the latter being responsible for the increased amounts of dioxygen observed with Fe(III) reagents by virtue of disproportionation paths. 

C-H Transformation at Unfunctionalized Alkanes Table 1. Ill ustrative examples of dioxirane-mediated C-H insertions. 

Unfunctionalized alkanes are a major feedstock for large-scale synthesis of intermediates and monomers in the chemical industry. They occur as mixtures in natural gas and are produced by cracking of light or heavy oil fractions. Higher al-... 

Scheme 1. Compilation of reactions and processes occurring during C—H transformation of small unfunctionalized alkane molecules...

In summary, catalytic C-H transformations in small unfunctionalized alkanes is a technically very important family of reactions and processes leading to small olefins or to aromatic compounds. The prototypical catalysts are chromia on alumina or vanadium oxides on basic oxide supports and platinum on alumina. Reaction conditions are harsh with a typical minimum temperature of 673 K at atmospheric pressure and often the presence of excess steam. A consistent view of the reaction pathway in the literature is the assumption that the first C-H abstraction should be the most difficult reaction step. It is noted that other than intuitive plausibility there is little direct evidence in heterogeneous reactions that this assumption is correct. From the fact that many of these reactions are highly selective toward aromatic compounds or olefins it must be concluded that later events in the sequence of elementary steps are possibly more likely candidates for the rate-determining step that controls the overall selectivity. A detailed description of the individual reactions of C2-C4 alkanes can be found in a comprehensive review [59]. 

Second, the strongest C-H bonds are the most desirable to functionalize with metal catalysts. Because radical reactions can be used to functionalize alkanes or alkyl chains at secondary C-H bonds, one target of catalytic alkane functionalization is the development of reactions at terminal C-H bonds. Because these C-H bonds are stronger than secondary and tertiary C-H bonds and because terminal carbons less readily support an accumulation of positive charge than internal carbons, many reactions of unfunctionalized C-H bonds occur less readily at primary C-H bonds than at secondary and tertiary C-H bonds. 

Afterwards, Antonchick and coworkers [105] successfully extended this methodology to the oxidative cross coupling of heteroarenes and simple unfunctionalized alkanes (Scheme 40 (1)). The new C(sp )-C(sp ) bond formation occurred selectively at the electron-deficient site of the arene. The reaction was... 

A number of examples have been reported documenting the use of palladium phosphine complexes as catalysts. The dialkyl species [PtL2R2] (L2 = dmpe, dppe, (PMe3)2 R = Me, CH2SiMe3) catalyze the reaction of [PhNH3]+ with activated alkenes (acrylonitrile, methyl acrylate, acrolein).176 Unfunctionalized alkenes prove unreactive. The reaction mechanism is believed to proceed via protonation of Pt-R by the ammonium salt (generating PhNH2 in turn) and the subsequent release of alkane to afford a vacant coordination site on the metal. Coordination of alkene then allows access into route A of the mechanism shown in Scheme 34. Protonation is also... 

When the C—H bond to be oxidized is proximate to a functional group, as we have stated already, its reactivity depends on the type of functional group. In the case of the hydroxy group, especially in secondary alcohols, these are more prone to dioxirane oxidation than their alkane precursors and, consequently, usually carbonyl products are obtained as the final product. Primary alcohols are less reactive, but may still be converted slowly to the corresponding aldehydes or carboxylic acids (due to the facile further oxidation of aldehydes)The functional-group transformation of the alcohols to ethers or acetals reduces the oxidative reactivity " but these C—H bonds are still more reactive than unfunctionalized ones. Thus, dioxirane oxidation of benzyl ether or acetal may... 

Alkanes are the world s most abundant organic resource. Olefins, by contrast, are relatively scarce they are, however, the most important class of intermediate in the commodity chemical industry [1], Thus the ability to convert alkanes to alkenes is a reaction with tremendous potential utility. Likewise, in view of the obvious importance of the carbon-carbon double bond functionality in the synthesis of complex organic molecules, the ability to introduce unsaturation into unfunctionalized alkyl groups is also a very alluring goal. 

One proposal for the catalytic cycle involves an Ir(III)-dihydride intermediate that forms after OA of H2 onto an Ir(I)-alkene complex. Experimental results seem to support this cycle,36 but computational studies suggest that the cycle involves Ir(III) and Ir(V) intermediates.37 The details of neither proposal have been elucidated. Work continues to expand the scope of this reaction to include asymmetric hydrogenation of any unfunctionalized alkene that could yield a chiral alkane. 

The reactions of C-H bonds in hydrocarbons with transition metal complexes to form products containing metal-carbon bonds, often termed "C-H activation," has been a topic of active study for decades because of the long-term goal of conducting selective synthesis with unfunctionalized reactants or unfunctionalized portions of more complex molecules. " Transformations of alkanes catalyzed by heterogeneous catalysts motivated the search for soluble species that could give rise to similar reactivity but with higher selectivity and at lower temperatures. 

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