Oxidation of alkenes to form epoxides

The simplest epoxide, ethylene oxide (or oxirane itself), can be produced on the tonne scale by the direct oxidation of ethene by oxygen at high temperature over a silver catalyst. These conditions are hardly suitable for general lab use, and the most commonly used epoxidizing agents are peroxy-carboxylic acids. Peroxy-acids (or peracids) have an extra oxygen atom between the carbonyl group and their acidic hydrogen—they are half-esters of hydrogen peroxide (H2O2). They are rather less acidic than carboxylic acids because their conjugate base is no longer stabilized by delocalization into the carbonyl group reagent. But they are electrophilic at oxygen, because attack there by a nucleophile displaces carboxylate, a good leaving group. [1]

Our epoxides

• 1,2-Epoxy-5-hexene [ CAS: 10353-53-4 ]
• (R)-(+)-1,2-Epoxy-5-hexene [ CAS: 137688-20-1 ]
• (S)-(-)-1,2-Epoxy-5-hexene [ CAS: 137688-21-2 ]
• 1,2-Epoxyoctane [ CAS: 2984-50-1 ]

Making peroxy-acids

Peroxy-acids are prepared from the corresponding acid anhydride and high-strength hydrogen peroxide. In general, the stronger the parent acid, the more powerful the oxidant (because the carboxylate is a better leaving group): one of the most powerfully oxidizing peroxy-acids is peroxy-trifluoroacetic acid. Hydrogen peroxide, at very high concentrations (> 80%), is explosive and difficult to transport. [1]

Epoxidation

The most commonly used peroxy-acid is known as m-CPBA, or meta-ChloroPeroxyBenzoicAcid. m-CPBA is a safely crystalline solid. Here it is, reacting with cyclohexene, to give the epoxide in 95% yield. [1]

The hydrolytic kinetic resolution (HKR) of terminal epoxides catalyzed by chiral (salen)Co^III complex affords both recovered unreacted epoxide and 1,2-diol product in highly enantioenriched form. As such, the HKR provides general access to useful, highly enantioenriched chiral building blocks that are otherwise difficult to access, from inexpensive racemic materials. The reaction has several appealing features from a practical standpoint, including the use of H₂O as a reactant and low loadings (0.2-2.0 mol %) of a recyclable, commercially available catalyst. In addition, the HKR displays extraordinary scope, as a wide assortment of sterically and electronically varied epoxides can be resolved to ≥99% ee. The corresponding 1,2-diols were produced in good-to-high enantiomeric excess using 0.45 equiv of H₂O. [2]

Jacobsen’s Salen(Co) Catalyst

This catalyst is composed of a large organic ligand complexed to cobalt. This type of organic ligand is referred to as a “salen”, so for shorthand we can refer to this as Jacobsen’s salen(Co) catalyst. There are a number of related catalysts in which the cobalt is replaced with another metal, for example, Mn, Al, or Cr.