Oxidations at Unfunctionalized Carbon

Attempts to achieve selective oxidations of hydrocarbons or other compounds when the desired site of attack is remote from an activating functional group are faced with several difficulties. With powerful transition-metal oxidants, the initial oxidation products are almost always more susceptible to oxidation than the starting material. When a hydrocarbon is oxidized, it is likely to be oxidized to a carboxylic acid, with chain cleavage by successive oxidation of alcohol and carbonyl intermediates. There are a few circumstances under which oxidations of hydrocarbons can be synthetically useful processes. One group involves catalytic industrial processes. Much effort has been expended on the development of selective catalytic oxidation processes and several have economic importance. We focus on several reactions that are used on a laboratory scale. 

Selective oxidations are possible for certain bicyclic hydrocarbons.285 Here, the bridgehead position is the preferred site of initial attack because of the order of reactivity of C—H bonds, which is 3° 2° 1°. The tertiary alcohols that are the initial oxidation products are not easily further oxidized. The geometry of the bicyclic rings (Bredt s rule) prevents both dehydration of the tertiary bridgehead alcohols and further oxidation to ketones. Therefore, oxidation that begins at a bridgehead position 

Other successful selective oxidations of hydrocarbons by Cr(VI) have been reported— for example, the oxidation of c/s-decalin to the corresponding alcohol—but careful attention to reaction conditions is required. 

Oxidation of trans-decalin leads to a mixture of 1- and 2-/ran.v-dccalonc.289 

The initial intermediates containing C-Fe bonds can be diverted by reagents such as CBrCl3 or CO, among others.290 

Organic Peroxides, John Wiley Sons, New York, 1992. 

Bailey, Ozonization in Organic Synthesis, Vols. I and II, Academic Press, New York, 1978, 1982. 

It has been difficult to formulate detailed reaction mechanisms for these oxidations, since several metal oxidation states are undoubtedly involved during the course of the reaction. In the case of permanganate, it is considered likely that 

Partial oxidations of side chains on aromatic compounds have also been achieved using tetraalkylammonium permanganates in organic solvents. 

These reagents, however, must be used with caution because of a potential danger of explosion. 

Benzeneseleninic anhydride is an effective reagent for oxidizing methyl groups on aromatic hydrocarbons and certain substituted aromatics to aldehydes. 

This reaction depends upon the facile solvolysis of )8-haloselenides and the oxidative elimination of selenium, which was discussed in Section 6.8.3. An alternative method, which is experimentally simpler, involves reaction of alkenes with a mixture of diphenyl diselenide and phenylseleninic acid. The two selenium reagents generate an electrophilic selenium species, phenylselenenic acid, PhSeOH. 

The elimination is promoted by oxidation to the selenoxide by t-butyl hydroperoxide. The regioselectivity in this reaction is such that the hydroxyl group becomes bound at the more substituted end of the carbon-carbon double bond. The origin of this orientation is that the addition follows Markownikoff s rule with PhSe acting as the electrophile. The elimination step specifically proceeds away from the oxygen functionality. 

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Chemical vapor deposition on carbon nanoflbers/tubes was described by Liang et al. [84]. Oxidized carbon nanoflbers were loaded in a fixed-bed reactor, and [Pd(allyl)Cp] was sublimed onto the fibers at 353 K. After reduction the final catalyst was obtained. The loading of Pd depended on the number of functional groups introduced by an HNO3 treatment. Unfunctionalized carbon nanofibers did not show any Pd uptake. Pt loadings of 2 to 4 wt% were typically obtained with Pd particle sizes of 2 to 4 nm. 

Guided by Marks s report of the samarium-catalyzed hydroboration of alkenes, Molander has developed a samarium-catalyzed protocol for the cyclization/hydroboration of unfunctionalized 1,6-dienes. In an optimized procedure, reaction of 1,5-hexadiene and l,3-dimethyl-l,3-diaza-2-boracyclopentane catalyzed by Gp 2Sm(THF) in toluene at room temperature for 18 h followed by oxidation gave hydroxymethylcyclopentane in 86% yield (Equation (70) R = H, n — ). The transformation was stereoselective, and Sm-catalyzed cyclization/hydroboration of 2-phenyl-1,5-hexadiene followed by oxidation formed /ra/ i--l-hydroxymethyl-2-phenylcyclopentane in 64% yield (Equation (70) R = Ph, n = ). The samarium-catalyzed reactions was also applicable to the synthesis of hydroxymethylcyclohexanes (Equation (70), n=X) but tolerated neither polar functionality nor substitution on the alkenyl carbon atoms. 

An example of the former is an amine (commonly AT-phenyl tetra-hydroisoquinoline, 1), which may be oxidized in a CDC reaction to give an imine, and an example of the latter is a malonate (e.g., 2) which may react as a carbon-based nucleophile upon tautomerization. The distinguishing feature of CDC reactions is that such species may be mixed in one pot, unfunctionalized, along with an oxidant. Of the multiple possible chemical pathways that can be envisaged in this melting pot, one predominates with sometimes striking selectivity, and it is this aspect of CDC reactions that has captured the attention of the research community.In this chapter we are concerned with the mechanisms of such reactions. 

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