| Jacobsen epoxidation | |
|---|---|
| Named after | Eric N. Jacobsen |
| Reaction type | Ring forming reaction |
| Identifiers | |
| Organic Chemistry Portal | jacobsen-katsuki-epoxidation |
| RSC ontology ID | RXNO:0000686 |
TheJacobsenepoxidation, sometimes also referred to asJacobsen-Katsuki epoxidation is achemical reaction which allowsenantioselective epoxidation of unfunctionalized alkyl- and aryl- substituted alkenes.[1][2][3] It is complementary to theSharpless epoxidation (used to formepoxides from the double bond inallylicalcohols). The Jacobsen epoxidation gains itsstereoselectivity from aC2symmetricmanganese(III)salen-like ligand, which is used incatalytic amounts. The manganese atom transfers an oxygen atom fromchlorine bleach or similar oxidant. The reaction takes its name from its inventor,Eric Jacobsen, withTsutomu Katsuki sometimes being included. Chiral-directing catalysts are useful to organic chemists trying to control the stereochemistry of biologically active compounds and developenantiopure drugs.
Several improved procedures have been developed.[4][5][6]
A general reaction scheme follows:[7]
In the early 1990s, Jacobsen and Katsuki independently released their initial findings about their catalysts for the enantioselective epoxidation of isolated alkenes.[1][3] 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.[2]
The degree of enantioselectivity depends on numerous factors, namely the structure of the alkene, the nature of the axial donor ligand on the activeoxomanganese species and the reaction temperature. Cyclic and acycliccis-1,2-disubstituted alkenes are epoxidized with almost 100% enantioselectivity whereastrans-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.[8]
The enantioselectivity is explained by either a "top-on" approach (Jacobsen) or by a "side-on" approach (Katsuki) of the alkene.
The mechanism of the Jacobsen–Katsuki epoxidation is not fully understood, but most likely a manganese(V)-species (similar to theferryl intermediate ofCytochrome P450) 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 catalyst) 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.[2][3]
The radical intermediate accounts for the formation of mixed epoxides when conjugated dienes are used as substrates.[8]
Dimethyldioxirane can be used as a source of O atoms. DMD of a chiral metal catalyst followed by epoxidation, or (2) epoxidation by chiral dioxiranes, which are generatedin situ from a catalytic amount of ketone and a stoichiometric amount of a terminal oxidant).[9] Mn-salen complexes have been used with success to accomplish the first strategy.[10]
