C-H oxidation has a long history and an ongoing presence in research at the forefront of chemistry and interrelated fields. As such, numerous highly useful articles and reviews have been written on this subject. Logically, these are generally written from the perspective of the scope and limitations of the reagents employed. This Minireview instead attempts to emphasize chemoselectivity imposed by the nature of the substrate. Consequently, many landmark discoveries in the field of C-H oxidation are not discussed, but hopefully the perspective taken herein will allow C-H oxidation reactions to be more readily incorporated into synthetic planning.

/pdf/if-c-h-bonds-could-talk-selective-c-h-bond-oxidation-3n1lbwrvjm.pdf

If C-H bonds could talk: selective C-H bond oxidation.

The advent of modern C–H functionalization chemistries has enabled medicinal chemists to consider a synthetic strategy, late stage functionalization (LSF), which utilizes the C–H bonds of drug leads as points of diversification for generating new analogs. LSF approaches offer the promise of rapid exploration of structure activity relationships (SAR), the generation of oxidized metabolites, the blocking of metabolic hot spots and the preparation of biological probes. This review details a toolbox of intermolecular C–H functionalization chemistries with proven applicability to drug-like molecules, classified by regioselectivity patterns, and gives guidance on how to systematically develop LSF strategies using these patterns and other considerations. In addition, a number of examples illustrate how LSF approaches have been used to impact actual drug discovery and chemical biology efforts.

The medicinal chemist's toolbox for late stage functionalization of drug-like molecules

Laboratory for Advanced Materials and New Catalysis, School of Chemistry and Materials Science, Hubei University, Wuhan 430062, China,Laboratory of Natural Gas Utilization and Applied Catalysis, Dalian Institute of Chemical Physics of Chinese Academy of Sciences, Dalian 116023,China, and Jingmen Technological College, Jingmen 448000, ChinaReceived June 30, 2004

Advances in Homogeneous and Heterogeneous Catalytic Asymmetric Epoxidation

Methylene C-H bonds are among the most difficult chemical bonds to selectively functionalize because of their abundance in organic structures and inertness to most chemical reagents. Their selective oxidations in biosynthetic pathways underscore the power of such reactions for streamlining the synthesis of molecules with complex oxygenation patterns. We report that an iron catalyst can achieve methylene C-H bond oxidations in diverse natural-product settings with predictable and high chemo-, site-, and even diastereoselectivities. Electronic, steric, and stereoelectronic factors, which individually promote selectivity with this catalyst, are demonstrated to be powerful control elements when operating in combination in complex molecules. This small-molecule catalyst displays site selectivities complementary to those attained through enzymatic catalysis.

http://science.sciencemag.org/content/sci/327/5965/566.full.pdf

Combined effects on selectivity in Fe-catalyzed methylene oxidation.

Polycyclic aromatic hydrocarbons (PAH) emitted from fluidized bed combustion have been reviewed. Firstly, the PAH origin is undertaken. Secondly, the state of the art on their sampling and analytical procedures are commented. Finally, the influence of the fuel, fossil and nonfossil fuels, the combustor type and the combustion variables are analyzed concerning PAH formation and emission in solid/gaseous phase.

A Review on Polycyclic Aromatic Hydrocarbon (PAH) Emissions from Energy Generation

Oxidations by methyl(trifluoromethyl)dioxirane. II: Oxyfunctionalization of saturated hydrocarbons

Kinetics and 180-labeling experiments have provided evidence for the involvment of dioxirane intermediates 2a (Scheme I) in the ketone-catalyzed decomposition of potassium peroxomonosulfate (KHS05, hereafter called caroate) .1-3 It has been shown that, under the reaction conditions (in water, pH 7.5, 2-10 “C), the side reaction involving Bayer-Villiger (BV) oxidation of the ketone (path iii) is negligible with most ketones (acetone, dialkyl ketones, acetophenones, etc.), whereas it becomes significant a t lower pH values or with ketones having certain structural features (e.g., cyclobutanone, cy~lopentanone).l-~ In competition with path i, amounting to ketone catalysis of caroate decomposition, the dioxirane intermediate is capable of oxidizing nucleophilic organic and inorganic substrates (S:, path ii).1-3 As an example, oxidation of phenylpropiolic acid, PhC=CC02H, a substrate representative of weakly nucleophilic alkynes, could be achieved by the caroate--ketone s y ~ t e m ; ~ ? ~ this is indicative of the high reactivity of intermediate 2a, as the mentioned alkyne resisted all attempts a t oxidation by peroxoacids (as well as by caroate in absence of ketones) under the given conditions. Similarly, trans-cinammic acid (3a) failed to react with alkaline hydrogen peroxide, m-chloroperoxobenzoic acid (MCPBA) in CHzClz or with caroate alone;3 however, as we have already reported, reaction of 3a with caroateacetone in water affords the trans-epoxide 3b in high yield. As the cis-epoxide 4b could also be obtained in high yield upon reaction of cis-cinammic acid (4a) with caroateacetone, the reaction appears to be highly stereospecific.2 We report here further data which illustrate the versatility of the caroate-acetone system as a generalized epoxidation method. These are shown in Table I. The synthesis of 4,5-epoxy-2-hexenoic acid (5b) in high yield, as the sole reaction product from sorbic acid (5a), shows that epoxidation via dioxirane can be remarkably regioselective. Notice that the sorbic acid 4,5 double bond, which is more nucleophilic, is selectively oxidized. Treatment of 5-hexen-2-one (6a) with caroate and acetone also affords the corresponding epoxide in high yield. It is not surprising, in this case, that caroate in the absence of acetone can also convert the alkene into the epoxide in high yield (although substrate conversion is lower). In fact,

Epoxidation of alkenes by dioxirane intermediates generated in the reaction of potassium caroate with ketones

On the isolation and characterization of methyl (trifluoromethyl) dioxirane

Chiral dioxirane intermediates, which are formed in the reaction of potassium peroxomonosulphate with chiral ketones, allow the epoxidation of simple pro-chiral olefins to the corresponding epoxides to be carried out with enantiomeric excesses in the range 9–12.5%.

Asymmetric epoxidation of unfunctionalized alkenes by dioxirane intermediates generated from potassium peroxomonosulphate and chiral ketones

Stereo- and regioselectivities in the epoxidation of some allylic alcohols by the dioxirane intermediate generated in the reaction of potassium caroate with acetone

Michele Fiorentino

Papers

Oxidations by methyl(trifluoromethyl)dioxirane. II: Oxyfunctionalization of saturated hydrocarbons

Epoxidation of alkenes by dioxirane intermediates generated in the reaction of potassium caroate with ketones

On the isolation and characterization of methyl (trifluoromethyl) dioxirane

Asymmetric epoxidation of unfunctionalized alkenes by dioxirane intermediates generated from potassium peroxomonosulphate and chiral ketones

Stereo- and regioselectivities in the epoxidation of some allylic alcohols by the dioxirane intermediate generated in the reaction of potassium caroate with acetone