Asymmetric catalytic oxidation is a technique of

oxidizing Redox ( , , reduction–oxidation or oxidation–reduction) is a type of chemical reaction in which the oxidation states of the reactants change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is ...

various

substrate Substrate may refer to: Physical layers *Substrate (biology), the natural environment in which an organism lives, or the surface or medium on which an organism grows or is attached ** Substrate (aquatic environment), the earthy material that exi ...

s to give an enantio-enriched product using a

catalyst Catalysis () is the increase in rate of a chemical reaction due to an added substance known as a catalyst (). Catalysts are not consumed by the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recycles quick ...

. Typically, but not necessarily, asymmetry is induced by the chirality of the catalyst. Typically, but again not necessarily, the methodology applies to organic substrates.

Functional group In organic chemistry, a functional group is any substituent or moiety (chemistry), moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions r ...

s that can be prochiral and readily susceptible to oxidation include certain

alkene In organic chemistry, an alkene, or olefin, is a hydrocarbon containing a carbon–carbon double bond. The double bond may be internal or at the terminal position. Terminal alkenes are also known as Alpha-olefin, α-olefins. The Internationa ...

s and

thioether In organic chemistry, a sulfide (British English sulphide) or thioether is an organosulfur functional group with the connectivity as shown on right. Like many other sulfur-containing compounds, Volatile organic compound, volatile sulfides have ...

s. Challenging but pervasive prochiral substrates are C-H bonds of alkanes. Instead of introducing oxygen, some catalysts, biological and otherwise, enantioselectively introduce halogens, another form of oxidation.

Reactions according to substrate

Hydrocarbons

Typically a prochiral C-H bond is converted to a chiral alcohol. Many examples of this important reaction result from the action of

cytochrome P450 Cytochromes P450 (P450s or CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for examp ...

, which allows these enzymes to process

prodrug A prodrug is a pharmacologically inactive medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be ...

s and

xenobiotic A xenobiotic is a chemical substance found within an organism that is not naturally produced or expected to be present within the organism. It can also cover substances that are present in much higher concentrations than are usual. Natural compo ...

Alpha-ketoglutarate-dependent hydroxylases Alpha-ketoglutarate-dependent hydroxylases are a major class of non-heme iron proteins that catalyse a wide range of reactions. These reactions include hydroxylation reactions, demethylations, ring expansions, ring closures, and desaturations. Func ...

also catalyze hydroxylations.

Alkenes

The oxidation of alkenes has attracted much attention. Asymmetric epoxidation is often feasible. One named reaction is the

Jacobsen epoxidation The Jacobsen epoxidation, sometimes also referred to as Jacobsen-Katsuki epoxidation is a chemical reaction which allows enantioselective epoxidation of unfunctionalized alkyl- and aryl- substituted alkenes. It is complementary to the Sharpless ...

, which uses manganese- salen complex as a chiral catalyst and NaOCl as the oxidant. The

Sharpless epoxidation The Sharpless epoxidation reaction is an enantioselective chemical reaction to prepare 2,3-epoxyalcohols from primary and secondary allylic alcohols. The oxidizing agent is ''tert''-butyl hydroperoxide. The method relies on a catalyst formed f ...

using chiral N-

heterocyclic A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different elements as members of its ring(s). Heterocyclic organic chemistry is the branch of organic chemistry dealing with the synthesis, proper ...

ligands and

osmium tetroxide Osmium tetroxide (also osmium(VIII) oxide) is the chemical compound with the formula OsO4. The compound is noteworthy for its many uses, despite its toxicity and the rarity of osmium. It also has a number of unusual properties, one being that the ...

. Instead of asymmetric epoxidation, alkenes are susceptible to asymmetric dihydroxylation. The method is especially applicable to

allyl alcohol Allyl alcohol (IUPAC name: prop-2-en-1-ol) is an organic compound with the structural formula . Like many alcohols, it is a water-soluble, colourless liquid. It is more toxic than typical small alcohols. Allyl alcohol is used as a precursor to ...

s using a catalyst derived from

titanium isopropoxide Titanium isopropoxide, also commonly referred to as titanium tetraisopropoxide or TTIP, is a chemical compound with the formula . This alkoxide of titanium(IV) is used in organic synthesis and materials science. It is a diamagnetic tetrahedral mol ...

and diethyl tartrate.

tert-Butyl hydroperoxide ''tert''-Butyl hydroperoxide (tBuOOH) is the organic compound with the formula (CH3)3COOH. It is one of the most widely used hydroperoxides in a variety of oxidation processes, like the Halcon process. It is normally supplied as a 69–70% aqueo ...

is the oxidant. This conversion, the

Sharpless asymmetric dihydroxylation Sharpless asymmetric dihydroxylation (also called the Sharpless bishydroxylation) is the chemical reaction of an alkene with osmium tetroxide in the presence of a chirality (chemistry), chiral quinine ligand to form a Vicinal (chemistry), vicinal ...

, was recognized by a

Nobel Prize The Nobel Prizes ( ; ; ) are awards administered by the Nobel Foundation and granted in accordance with the principle of "for the greatest benefit to humankind". The prizes were first awarded in 1901, marking the fifth anniversary of Alfred N ...

. Metal-free asymmetric olefin oxidation have been developed. For example, the

Shi epoxidation The Shi epoxidation is a chemical reaction described as the asymmetric epoxidation of alkenes with oxone (potassium peroxymonosulfate) and a fructose-derived catalyst (1). This reaction is thought to proceed via a dioxirane intermediate, generate ...

of alkenes using

oxone Potassium peroxymonosulfate is widely used as an oxidizing agent, for example, in pools and spas (usually referred to as monopersulfate or "MPS"). It is the potassium salt of peroxymonosulfuric acid. Potassium peroxymonosulfate per se is rarely e ...

can be made asymmetric using a

fructose Fructose (), or fruit sugar, is a Ketose, ketonic monosaccharide, simple sugar found in many plants, where it is often bonded to glucose to form the disaccharide sucrose. It is one of the three dietary monosaccharides, along with glucose and gal ...

-derived catalyst.

Sulfur compounds

The enantioselective oxidation of unsymmetrical thioethers to

sulfoxide In organic chemistry, a sulfoxide, also called a sulphoxide, is an organosulfur compound containing a sulfinyl () functional group attached to two carbon atoms. It is a polar functional group. Sulfoxides are oxidized derivatives of sulfides. E ...

s is a well established. The common over the counter medication

Esomeprazole Esomeprazole, sold under the brand name Nexium r Neksiumamong others, is a medication which reduces stomach acid. It is used to treat gastroesophageal reflux disease, peptic ulcer disease, and Zollinger–Ellison syndrome. Its effectiveness ...

(brandname: Nexium) involves such an asymmetric oxidation as its final step. Even disulfides are susceptible to oxidation to chiral thiosulfinites.

References

{{Chiral synthesis Catalysis