The Jacobsen

epoxidation In organic chemistry, an epoxide is a cyclic ether () with a three-atom ring. This ring approximates an equilateral triangle, which makes it strained, and hence highly reactive, more so than other ethers. They are produced on a large scale ...

, sometimes also referred to as Jacobsen-Katsuki epoxidation is a

chemical reaction A chemical reaction is a process that leads to the IUPAC nomenclature for organic transformations, chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the pos ...

which allows

enantioselective In chemistry, an enantiomer ( /ɪˈnænti.əmər, ɛ-, -oʊ-/ ''ih-NAN-tee-ə-mər''; from Ancient Greek ἐνάντιος ''(enántios)'' 'opposite', and μέρος ''(méros)'' 'part') – also called optical isomer, antipode, or optical anti ...

epoxidation of unfunctionalized alkyl- and aryl- substituted alkenes. It is complementary to 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 fro ...

(used to form

epoxides In organic chemistry, an epoxide is a cyclic ether () with a three-atom ring. This ring approximates an equilateral triangle, which makes it strained, and hence highly reactive, more so than other ethers. They are produced on a large scale f ...

from the double bond in allylic alcohols). The Jacobsen epoxidation gains its

stereoselectivity In chemistry, stereoselectivity is the property of a chemical reaction in which a single reactant forms an unequal mixture of stereoisomers during a non-stereospecific creation of a new stereocenter or during a non-stereospecific transformation of ...

from a ''C₂''

symmetric Symmetry (from grc, συμμετρία "agreement in dimensions, due proportion, arrangement") in everyday language refers to a sense of harmonious and beautiful proportion and balance. In mathematics, "symmetry" has a more precise definiti ...

manganese(III) salen-like ligand, which is used in

catalytic Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...

amounts. The manganese atom transfers an oxygen atom from chlorine bleach or similar oxidant. The reaction takes its name from its inventor, Eric Jacobsen, with

Tsutomu Katsuki Tsutomu Katsuki (September 23, 1946 – October 13, 2014) was an organic chemist who primarily focused on asymmetric oxidation reactions utilizing transition metal catalysts. Education Katsuki performed doctoral studies in the lab of Masaru Ya ...

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

enantiopure drug An enantiopure drug is a pharmaceutical that is available in one specific enantiomeric form. Most biological molecules (proteins, sugars, etc.) are present in only one of many chiral forms, so different enantiomers of a chiral drug molecule bind d ...

s. Several improved procedures have been developed. A general reaction scheme follows: : General Jacobsen reaction

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 (Jacobsen) or by a "side-on" approach (Katsuki) of the alkene.

Mechanism

The mechanism of the Jacobsen–Katsuki epoxidation is not fully understood, but most likely a manganese(V)-species (similar to the

ferryl A transition metal oxo complex is a coordination complex containing an oxo ligand. Formally O2-, an oxo ligand can be bound to one or more metal centers, i.e. it can exist as a terminal or (most commonly) as bridging ligands (Fig. 1). Oxo ligan ...

intermediate of

Cytochrome P450 Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various co ...

) 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. : Mechanism of the Jacobsen catalytic enantioselective epoxidation

Mechanism of the Jacobsen catalytic enantioselective epoxidation

The radical intermediate accounts for the formation of mixed epoxides when conjugated dienes are used as substrates. : Mechanisms of the free-radical and metallo-oxetane pathways of the Jacobsen-Katsuki reaction

Mechanisms of the free-radical and metallo-oxetane pathways of the Jacobsen-Katsuki reaction

References

{{Reflist Epoxidation reactions Organic oxidation reactions Name reactions