The Jacobsen Epoxidation, sometimes also referred to as Jacobsen-Katsuki Epoxidation is a chemical reaction

Chemical reaction

A chemical reaction is a process that leads to the transformation of one set of chemical substances to another. Chemical reactions can be either spontaneous, requiring no input of energy, or non-spontaneous, typically following the input of some type of energy, such as heat, light or electricity...

 which allows enantioselective epoxidation of unfunctionalized alkyl- and aryl- substituted olefins. It is complementary to the Sharpless epoxidation

Sharpless epoxidation

The Sharpless Epoxidation reaction is an enantioselective chemical reaction to prepare 2,3-epoxyalcohols from primary and secondary allylic alcohols....

 (used to form epoxides from the double bond in allyl

Allyl

An allyl group is a substituent with the structural formula H2C=CH-CH2R, where R is the connection to the rest of the molecule. It is made up of a methylene , attached to a vinyl group . The name is derived from the Latin word for garlic, Allium sativum. Theodor Wertheim isolated an allyl...

ic alcohols). The Jacobsen epoxidation gains its stereoselectivity from a C₂ symmetric

Molecular symmetry

Molecular symmetry in chemistry describes the symmetry present in molecules and the classification of molecules according to their symmetry. Molecular symmetry is a fundamental concept in chemistry, as it can predict or explain many of a molecule's chemical properties, such as its dipole moment...

 manganese(III)

Manganese

Manganese is a chemical element, designated by the symbol Mn. It has the atomic number 25. It is found as a free element in nature , and in many minerals...

 salen-like ligand

Salen ligand

Salen is the abbreviation for a popular chelating ligand used in coordination chemistry and homogeneous catalysis. The name salen is a contraction for salicylaldehyde and ethylenediamine. The ligand is a bright yellow micaceous solid that is soluble in polar organic solvents.-Nomenclature:The...

, which is used in catalytic

Catalysis

Catalysis is the change in rate of a chemical reaction due to the participation of a substance called a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. A catalyst may participate in multiple chemical transformations....

 amounts. The manganese atom transfers an oxygen atom from chlorine bleach or similar oxidant. The reaction is named after its inventor, Eric Jacobsen

Eric Jacobsen

Eric N. Jacobsen is the Sheldon Emery Professor of Chemistry in the Department of Chemistry and Chemical Biology at Harvard University...

, currently of Harvard University

Harvard University

Harvard University is a private Ivy League university located in Cambridge, Massachusetts, United States, established in 1636 by the Massachusetts legislature. Harvard is the oldest institution of higher learning in the United States and the first corporation chartered in the country...

. Chiral-directing catalysts are useful to organic chemists trying to control the stereochemistry of biologically active compounds and develop enantiopure drug

Enantiopure drug

An enantiopure drug is a pharmaceutical that is available in one specific enantiomeric form. Most biological molecules are present in only one of many chiral forms, so different enantiomers of a chiral drug molecule bind differently to target receptors...

s.

Several improved procedures have been developed.

A general reaction scheme follows:

History

In the early 1990s, Jacobsen and Katsuki independently released their initial findings about their catalysts for the enantioselective epoxidation of isolated alkenes. In 1991, Jacobsen published work where he attempted to perfect the catalyst. He was able to obtain ee values above 90% for a variety of ligands. Also, the amount of catalyst used was no more than 15% of the amount of alkene used in the reaction.

General Features

The degree of enantioselectivity depends on numerous factors, namely the structure of the olefin, the nature of the axial donor ligand on the active oxomanganese species and the reaction temperature. Cyclic and acyclic (Z)-1,2-disubstituted olefins are epoxidized with almost 100% enantioselectivity whereas (E)-1,2-disubstituted olefins are poor substrates for Jacobsen's catalysts but yet give higher enantioselectivities when Katsuki's catalysts are used. Furthermore, the enantioselective epoxidation of conjugated dienes is much higher than that of the nonconjugated dienes.

The enantioselectivity is explained by either a "top-on" approach (Jacobsen) or by a "side-on" approach (Katsuki) of the olefin.

Mechanism

The mechanism of the Jacobsen-Katsuki epoxidation is not fully understood, but most likely a manganese(V)-species is the reactive intermediate which is formed upon the oxidation of the Mn(III)-salen complex. There are three major pathways. The concerted pathway, the metalla oxetane pathway and the radical pathway. The most accepted mechanism is the concerted pathway mechanism. After the formation of the Mn(V) complex, the catalyst is activated and therefore can form epoxides with alkenes. The alkene comes in from the "top-on" approach (above the plane of the catayst) and the Oxygen atom now is bonded to the two Carbon atoms (previously C=C bond) and is still bonded to the Manganese metal. Then, the Mn--O bond breaks and the epoxide is formed. The Mn(III)-salen complex is regenerated, which can then be oxidized again to form the Mn(V) complex.

The radical intermediate accounts for the formation of mixed epoxides when conjugated olefins are used as substrates.