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 epoxidation. The Jacobsen epoxidation gains its stereoselectivity from a C2 symmetric manganese salen-like ligand, which is used in catalytic amounts. The manganese atom transfers an oxygen atom from chlorine bleach or similar oxidant. The reaction is named after its inventor, Eric Jacobsen, and sometimes also including Tsutomu Katsuki. Chiral-directing catalysts are useful to organic chemists trying to control the stereochemistry of biologically active compounds and develop enantiopure drugs.
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 alkene, the nature of the axial donor ligand on the active oxomanganese species and the reaction temperature. Cyclic and acyclic cis-1,2-disubstituted alkenes are epoxidized with almost 100% enantioselectivity whereas trans-1,2-disubstituted alkenes 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 or by a "side-on" approach of the alkene.

Mechanism

The mechanism of the Jacobsen–Katsuki epoxidation is not fully understood, but most likely a manganese-species is the reactive intermediate which is formed upon the oxidation of the Mn-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 complex, the catalyst is activated and therefore can form epoxides with alkenes. The alkene comes in from the "top-on" approach and the oxygen atom now is bonded to the two carbon atoms and is still bonded to the manganese metal. Then, the Mn–O bond breaks and the epoxide is formed. The Mn-salen complex is regenerated, which can then be oxidized again to form the Mn complex.
The radical intermediate accounts for the formation of mixed epoxides when conjugated dienes are used as substrates.